Ronald L. Dalman MD

All Publications

• Exercise Training Improves Ventilatory Efficiency in Patients With a Small Abdominal Aortic Aneurysm: A RANDOMIZED CONTROLLED STUDY. Journal of cardiopulmonary rehabilitation and prevention Lima, R. M., Vainshelboim, B., Ganatra, R., Dalman, R., Chan, K., Myers, J. 2018; 38 (4): 239–45

  Abstract

  PURPOSE: To investigate the effects of exercise training on ventilatory efficiency and physiological responses to submaximal exercise in subjects with small abdominal aortic aneurysm (AAA).METHODS: Sixty-five male patients (72.3 ± 7.0 years) were randomized to exercise training (n = 33) or usual care group (n = 32). Exercise subjects participated in a training groups for 3 mo. Cardiopulmonary exercise testing was performed before and after the study period and peak (Equation is included in full-text article.)O2, the ventilatory threshold (VT), the oxygen uptake efficiency slope (OUES), and the (Equation is included in full-text article.)E2/(Equation is included in full-text article.)CO2 slope were identified. Baseline work rates at VT were matched to examine cardiopulmonary responses after training.RESULTS: Significant interactions indicating improvements before and after training in the exercise group were noted for time (P < .01), (Equation is included in full-text article.)O2 (P < .01), and work rate (P < .01) at the VT. At peak effort, significant interactions were noted for time (P < .01) and work rate (P < .01), while borderline significance was noted for absolute (P = .07) and relative (P = .04) (Equation is included in full-text article.)O2. Significant interactions were observed for the OUES both when using all exercise data (P = .04) and when calculated up to the VT (P < .01). For the (Equation is included in full-text article.)E2/(Equation is included in full-text article.)CO2 slope, significance was noted only when calculated up to the VT (P = .04). After training, heart rate, (Equation is included in full-text article.)E, (Equation is included in full-text article.)O2 and respiratory exchange ratio were significantly attenuated for the same baseline work rate only in the exercise group (all P < .01).CONCLUSIONS: Exercise training improves ventilatory efficiency in patients with small AAA. In addition, patients who exercised exhibited less demanding cardiorespiratory responses to submaximal effort.

  View details for DOI 10.1097/HCR.0000000000000270

  View details for PubMedID 28727673

• Identification of optimal device combinations for the chimney endovascular aneurysm repair technique within the PERICLES registry JOURNAL OF VASCULAR SURGERY Scali, S. T., Beck, A. W., Torsello, G., Lachat, M., Kubilis, P., Veith, F. J., Lee, J. T., Donas, K. P., PERICLES Investigators 2018; 68 (1): 24–35

  Abstract

  The ideal stent combination for chimney endovascular aneurysm repair remains undetermined. Therefore, we sought to identify optimal aortic and chimney stent combinations that are associated with the best outcomes by analyzing the worldwide collected experience in the PERformance of chImney technique for the treatment of Complex aortic pathoLogiES (PERICLES) registry.The PERICLES registry was reviewed for patients with pararenal aortic disease electively treated from 2008 to 2014. Eleven different aortic devices were identified with three distinct subgroups: group A (n = 224), nitinol/polyester; group B (n = 105), stainless steel/polyester; and group C (n = 69), nitinol/expanded polytetrafluoroethylene. The various chimney stent subtypes included the balloon-expandable covered stent (BECS), self-expanding covered stent, and bare-metal stent. Deidentified aortic and chimney device combinations were compared for risk of chimney occlusion, type IA endoleak, and survival. Effects of high-volume centers (>100 cases), use of an internal lining chimney stent, number of chimney stents, and number of chimney stent subtypes deployed were also considered. We considered demographics, comorbidities, and aortic anatomic features as potential confounders in all models.The 1- and 3-year freedom from BECS chimney occlusion was not different between groups (group A, 96% ± 2% and 87% ± 5%; groups B and C, 93% ± 3% and 76% ± 10%; Cox model, P = .33). Similarly, when non-BECS chimney stents were used, no difference in occlusion risk was noted for the three aortic device groupings; however, group C patients receiving BECS did have a trend toward higher occlusion risk relative to group C patients not receiving a BECS chimney stent (hazard ratio [HR], 4.0; 95% confidence interval [CI], 0.85-18.84; P = .08). Patients receiving multiple chimney stents, irrespective of stent subtype, had a 1.8-fold increased risk of occlusion for each additional stent (HR, 1.8; 95% CI, 1.2-2.9; P = .01). Use of a bare-metal endolining stent doubled the occlusion hazard (HR, 2.1; 95% CI, 1.0-4.5; P = .05). Risk of type IA endoleak (intraoperatively and postoperatively) did not significantly differ for the aortic devices with BECS use; however, group C patients had higher risk relative to groups A/B without BECS (C vs B: odds ratio [OR], 3.2 [95% CI, 1-11; P = .05]; C vs A/B: OR, 2.4 [95% CI, 0.9-6.4; P = .08]). Patients treated at high-volume centers had significantly lower odds for development of type IA endoleak (OR, 0.2; 95% CI, 0.1-0.7; P = .01) irrespective of aortic or chimney device combination. Mortality risk was significantly higher in group C + BECS vs group A + BECS (HR, 5.3; 95% CI, 1.6-17.5; P = .006). The 1- and 3-year survival for groups A, B, and C (+BECS) was as follows: group A, 97% ± 1% and 92% ± 3%; group B, 93% ± 3% and 83% ± 7%; and group C, 84% ± 7% and 63% ± 14%. Use of more than one chimney subtype was associated with increased mortality (HR, 3.2; 95% CI, 1.4-7.5; P = .006).Within the PERICLES registry, use of nitinol/polyester stent graft devices with BECS during chimney endovascular aneurysm repair is associated with improved survival compared with other aortic endografts. However, this advantage was not observed for non-BECS repairs. Repairs incorporating multiple chimney subtypes were also associated with increased mortality risk. Importantly, increasing chimney stent number and bare-metal endolining stents increase chimney occlusion risk, whereas patients treated at low-volume centers have higher risk of type IA endoleak.

  View details for DOI 10.1016/j.jvs.2017.10.080

  View details for Web of Science ID 000436836800005

  View details for PubMedID 29395423

• Episode-based cost reduction for endovascular aneurysm repair. Journal of vascular surgery Itoga, N. K., Tang, N., Patterson, D., Ohkuma, R., Lew, R., Mell, M. W., Dalman, R. L. 2018

  Abstract

  OBJECTIVE: Effective strategies to reduce costs associated with endovascular aneurysm repair (EVAR) remain elusive for many medical centers. In this study, targeted interventions to reduce inpatient EVAR costs were identified and implemented.METHODS: From June 2015 to February 2016, we analyzed the EVAR practice at a high-volume academic medical center to identify, to rank, and ultimately to reduce procedure-related costs. In this analysis, per-patient direct costs to the hospital were compared before (September 2013-May 2015) and after (March 2016-January 2017) interventions were implemented. Improvement efforts concentrated on three categories that accounted for a majority of costs: implants, rooming costs, and computed tomography scans performed during the index hospitalization.RESULTS: Costs were compared between 141 EVAR procedures before implementation (PRE period) and 47 EVAR procedures after implementation (POST period). Based on data obtained through the Society for Vascular Surgery EVAR Cost Demonstration Project, it was determined that implantable device costs were higher than those at peer institutions. New purchasing strategies were implemented, resulting in a 30.8% decrease in per-case device costs between the PRE and POST periods. Care pathways were modified to reduce use of and costs for computed tomography scans obtained during the index hospitalization. Compared with baseline, per-case imaging costs decreased by 92.9% (P< .001), including a 99.0% (P= .001) reduction in postprocessing costs. Care pathways were also implemented to reduce preprocedural rooming for patients traveling long distances the day before surgery, resulting in a 50% decrease in utilization rate (35.4% PRE to 17.0% POST; P= .021), without having a significant impact on median postprocedural length of stay (PRE, 2days [interquartile range, 1-11days]; POST, 2days [1-7days]; P= .185). Medication costs also decreased by 38.2% (P< .001) as a hospital-wide effort.CONCLUSIONS: Excessive costs associated with EVAR threaten the sustainability of these procedures in health care organizations. Targeted cost reduction efforts can effectively reduce expenses without compromising quality or limiting patients' access.

  View details for DOI 10.1016/j.jvs.2018.04.043

  View details for PubMedID 30185384

• Clinical Impact of a Wound Care Center on a Vascular Surgery Practice Flores, A. M., Mell, M. W., Dalman, R. L., Chandra, V. MOSBY-ELSEVIER. 2018: E88–E89

  View details for Web of Science ID 000433036700079

• Metformin Prescription Status and Abdominal Aortic Aneurysm Disease Progression in the US Veteran Patient Population Itoga, N. K., Rothenberg, K. A., Suarez, P., Vy Thuy Ho, Mell, M. W., Xu, B., Curtin, C. M., Dalman, R. L. MOSBY-ELSEVIER. 2018: E52

  View details for Web of Science ID 000433036700010

• Long-term outcomes after repair of symptomatic abdominal aortic aneurysms. Journal of vascular surgery Chandra, V., Trang, K., Virgin-Downey, W., Dalman, R. L., Mell, M. W. 2018

  Abstract

  OBJECTIVES: Previous studies have reported increased perioperative mortality of nonruptured symptomatic abdominal aortic aneurysms (Sx-AAA) compared with asymptomatic elective AAA (E-AAA) repairs, but no long-term-outcomes have been reported. We sought to compare long-term outcomes of Sx-AAA and E-AAA after repair at a single academic institution.METHODS: Patients receiving AAA repair for Sx-AAA and E-AAA from 1995 through 2015 were included. Ruptured AAA and suprarenal or thoracoabdominal AAA were excluded. Demographics, comorbidities, and operative approach were collected. Long-term mortality was the primary outcome, determined by chart review or link to Social Security Death Index. Additionally, long-term mortality and reinterventions were compared after groups were matched with nearest neighbor propensity to reduce bias.RESULTS: AAA repair was performed for 1054 E-AAA (383 open repair [36%], 671 endovascular aneurysm repair [EVAR] [64%]), and 139 symptomatic aneurysms (60 open repair [43%], 79 EVAR [57%]). Age (73years vs 74years; P= .13) and aneurysm diameter were similar between Sx-AAA and E-AAA (6.0cm vs 5.8cm; P= .5). The proportion of women was higher for Sx-AAA (26% vs 16%; P= .003), as was the proportion of non-Caucasians (40% vs 29%; P= .009). After propensity matching, there were no differences between groups for patient characteristics, AAA diameter, treatment modality, or comorbidities, including hypertension, coronary artery disease, congestive heart failure, diabetes, hyperlipidemia, lung disease, diabetes, renal disease, and smoking history. Women were treated for Sx-AAA at significantly smaller aortic diameters; however, compared with men (5.1cm vs 6.3cm; P< .001). Perioperative mortality was 5.0% for Sx-AAA and 2.3% for E-AAA (P= .055). By life-table analysis, Sx-AAA had lower 5-year (62% vs 71%) and 10-year (39% vs 51%) survivals (P= .01) compared with E-AAA for the entire cohort. Similar trends were observed for 5-year and 10-year mortality after propensity matching (63% and 40% vs 71% and 52%; P= .05). When stratified by repair type 5-year and 10-year survivals trended lower after open surgery (68% and 42% Sx-AAA vs 84% and 59% E-AAA; P= .08) but not EVAR (59% and 40% Sx-AAA vs 61% and 49% E-AAA; P= .4). Aneurysm-related reinterventions were similar for Sx-AAA and E-AAA (15% vs 14%; P= .8). Reinterventions were more common after EVAR compared with open repair (22% vs 7%, Sx-AAA P= .015; 20% vs 4% E-AAA; P= .007).CONCLUSIONS: Patients with Sx-AAA had lower long-term survival and similar aneurysm-related reinterventions compared with patients with E-AAA undergoing repair. Women also underwent repair for Sx-AAA at a significantly smaller size when compared with men, which emphasizes the role of gender in AAA symptomatology. Differences in long-term survival may be only partially explained by measured patient, aneurysm, and operative factors, and may reflect unmeasured social factors or suggest inherent differences in pathophysiology of Sx-AAAs.

  View details for DOI 10.1016/j.jvs.2018.02.036

  View details for PubMedID 29705087

• Proefferocytic Therapy Promotes Transforming Growth Factor-beta Signaling and Prevents Aneurysm Formation CIRCULATION Kojima, Y., Werner, N., Ye, J., Nanda, V., Tsao, N., Wang, Y., Flores, A. M., Miller, C. L., Weissman, I., Deng, H., Xu, B., Dalman, R. L., Eken, S. M., Pelisek, J., Li, Y., Maegdefessel, L., Leeper, N. J. 2018; 137 (7): 750–53

  View details for DOI 10.1161/CIRCULATIONAHA.117.030389

  View details for Web of Science ID 000424954800015

  View details for PubMedID 29440201

  View details for PubMedCentralID PMC5819616

• Pathogenic and therapeutic significance of angiotensin II type I receptor in abdominal aortic aneurysms. Current drug targets Xu, B., Xuan, H., Iida, Y., Miyata, M., Dalman, R. L. 2018

  Abstract

  BACKGROUND: Abdominal aortic aneurysm (AAA) is a chronic degenerative inflammatory disease. Multi-factors including genetic, environmental and lifestyles determine the onsets and progression of AAAs. Currently surgical repair remains the only effective aneurysm treatment, but no pharmacological therapy is available for limiting further enlargement of small AAAs and fetal rupture.OBJECTIVE: This article is to review our current understanding of angiotensin II (Ang II) and its type 1 receptor (AT1) in AAA pathogenesis as well as the translational potential of AT1 receptor blocker (ARB) treatment for treating clinical AAA disease.RESULTS: While many pathways or molecules have been shown to associate with AAA formation and progression, accumulating evidence indicates the most significant importance of peptide hormone angiotensin II (Ang II) and its type 1 receptor (AT1) in AAA pathogenesis and suggest the translational value of targeting inhibition of AT1 in treating clinical AAA disease. This review summarized the influences of genetic angiotensin II type 1 (AT1) receptor deficiency and pharmacological AT1 receptor blocker (ARB) treatment on experimental AAAs. A discussion has also been made on whether and how ARB medication in AAA patients changes the natural course of clinical AAAs, including aneurysm enlargement rate, rupture and AAA-specific mortality. Additionally, we provided information on two registered clinical trials which are to test the efficacy of telmisartan and valsartan in limiting small AAA enlargement.CONCLUSIONS: Ang II/AT1 pathway plays a critical role in aneurysmal pathogenesis. Targeting AT1 via ARB will help establishing novel pharmacological therapies for limiting continuous enlargement of small AAAs in patients.

  View details for DOI 10.2174/1389450119666180122155642

  View details for PubMedID 29359665

• The Society for Vascular Surgery practice guidelines on the care of patients with an abdominal aortic aneurysm JOURNAL OF VASCULAR SURGERY Chaikof, E. L., Dalman, R. L., Eskandari, M. K., Jackson, B. M., Lee, W., Mansour, M., Mastracci, T. M., Mell, M., Murad, M., Nguyen, L. L., Oderich, G. S., Patel, M. S., Schermerhorn, M. L., Starnes, B. W. 2018; 67 (1): 2-+

  Abstract

  Decision-making related to the care of patients with an abdominal aortic aneurysm (AAA) is complex. Aneurysms present with varying risks of rupture, and patient-specific factors influence anticipated life expectancy, operative risk, and need to intervene. Careful attention to the choice of operative strategy along with optimal treatment of medical comorbidities is critical to achieving excellent outcomes. Moreover, appropriate postoperative surveillance is necessary to minimize subsequent aneurysm-related death or morbidity.The committee made specific practice recommendations using the Grading of Recommendations Assessment, Development, and Evaluation system. Three systematic reviews were conducted to support this guideline. Two focused on evaluating the best modalities and optimal frequency for surveillance after endovascular aneurysm repair (EVAR). A third focused on identifying the best available evidence on the diagnosis and management of AAA. Specific areas of focus included (1) general approach to the patient, (2) treatment of the patient with an AAA, (3) anesthetic considerations and perioperative management, (4) postoperative and long-term management, and (5) cost and economic considerations.Along with providing guidance regarding the management of patients throughout the continuum of care, we have revised a number of prior recommendations and addressed a number of new areas of significance. New guidelines are provided for the surveillance of patients with an AAA, including recommended surveillance imaging at 12-month intervals for patients with an AAA of 4.0 to 4.9 cm in diameter. We recommend endovascular repair as the preferred method of treatment for ruptured aneurysms. Incorporating knowledge gained through the Vascular Quality Initiative and other regional quality collaboratives, we suggest that the Vascular Quality Initiative mortality risk score be used for mutual decision-making with patients considering aneurysm repair. We also suggest that elective EVAR be limited to hospitals with a documented mortality and conversion rate to open surgical repair of 2% or less and that perform at least 10 EVAR cases each year. We also suggest that elective open aneurysm repair be limited to hospitals with a documented mortality of 5% or less and that perform at least 10 open aortic operations of any type each year. To encourage the development of effective systems of care that would lead to improved outcomes for those patients undergoing emergent repair, we suggest a door-to-intervention time of <90 minutes, based on a framework of 30-30-30 minutes, for the management of the patient with a ruptured aneurysm. We recommend treatment of type I and III endoleaks as well as of type II endoleaks with aneurysm expansion but recommend continued surveillance of type II endoleaks not associated with aneurysm expansion. Whereas antibiotic prophylaxis is recommended for patients with an aortic prosthesis before any dental procedure involving the manipulation of the gingival or periapical region of teeth or perforation of the oral mucosa, antibiotic prophylaxis is not recommended before respiratory tract procedures, gastrointestinal or genitourinary procedures, and dermatologic or musculoskeletal procedures unless the potential for infection exists or the patient is immunocompromised. Increased utilization of color duplex ultrasound is suggested for postoperative surveillance after EVAR in the absence of endoleak or aneurysm expansion.Important new recommendations are provided for the care of patients with an AAA, including suggestions to improve mutual decision-making between the treating physician and the patients and their families as well as a number of new strategies to enhance perioperative outcomes for patients undergoing elective and emergent repair. Areas of uncertainty are highlighted that would benefit from further investigation in addition to existing limitations in diagnostic tests, pharmacologic agents, intraoperative tools, and devices.

  View details for DOI 10.1016/j.jvs.2017.10.044

  View details for Web of Science ID 000419432400026

  View details for PubMedID 29268916

• Acute Type B Dissection Causing Collapse of EVAR Endograft and Iliac Limb Occlusion Itoga, N. K., Wu, T., Dake, M. D., Dalman, R. L., Lee, J. T. ELSEVIER SCIENCE INC. 2018: 206.e1–206.e4

  Abstract

  We describe a rare case of acute type B dissection (ATBDs) causing collapse of a previously placed infrarenal stent graft, resulting in acute limb ischemia due to left iliac limb thrombosis in a 59-year-old male. The patient presented with acute back and abdominal discomfort radiating to his back, bilateral buttock stabbing discomfort and left > right thigh and calf rest pain. CT angiography showed a spiral type B dissection with collapse of the proximal portion of the endovascular repair of aortic aneurysm (EVAR) device and left limb occlusion. Urgent treatment with thoracic endovascular aortic repair distal to the left subclavian covered the entry tear and redirected the majority of the flow to the true lumen leading to near immediate expansion of the proximal portion of the EVAR device. After surgical femoral control, balloon embolectomy of the occluded iliac limb was performed and the limb relined. His lower extremity ischemic symptoms resolved, and his abdominal and back pain dissipated. At latest 6-month follow-up, CT angiography shows an intact thoracic endovascular aortic repair stent graft and a widely patent EVAR stent graft, and the patient has no further abdominal, back, or leg symptoms. ATBD causing proximal abdominal EVAR collapse is an extremely rare presentation of false lumen pressurization and can be treated similarly to complicated type B dissection with the goal of restoring true lumen patency.

  View details for DOI 10.1016/j.avsg.2017.07.024

  View details for Web of Science ID 000418233100030

  View details for PubMedID 28739456

  View details for PubMedCentralID PMC5842241

• Hypoxia-inducible factor 1 in clinical and experimental aortic aneurysm disease. Journal of vascular surgery Wang, W., Xu, B., Xuan, H., Ge, Y., Wang, Y., Wang, L., Huang, J., Fu, W., Michie, S. A., Dalman, R. L. 2017

  Abstract

  OBJECTIVE: Mural angiogenesis and macrophage accumulation are two pathologic hallmarks of abdominal aortic aneurysm (AAA) disease. The heterodimeric transcription factor hypoxia-inducible factor 1 (HIF-1) is an essential regulator of angiogenesis and macrophage function. In this study, we investigated HIF-1 expression and activity in clinical and experimental AAA disease.METHODS: Human aortic samples were obtained from 24 AAA patients and six organ donors during open abdominal surgery. Experimental AAAs were created in 10-week-old male C57BL/6J mice by transient intra-aortic infusion of porcine pancreatic elastase (PPE). Expression of HIF-1alpha and its target gene messenger RNA (mRNA) levels were assessed in aneurysmal and control aortae. The HIF-1alpha inhibitors 2-methoxyestradiol and digoxin, the prolyl hydroxylase domain-containing protein (PHD) inhibitors cobalt chloride and JNJ-42041935, and the vehicle alone as control were administered daily to mice at varying time points beginning before or after PPE infusion. Influences on experimental AAA formation and progression were assessed by serial transabdominal ultrasound measurements of aortic diameter and histopathologic analysis at sacrifice.RESULTS: The mRNA levels for HIF-1alpha, vascular endothelial growth factor A, glucose transporter 1, and matrix metalloproteinase 2 were significantly increased in both human and experimental aneurysm tissue. Tissue immunostaining detected more HIF-1alpha protein in both human and experimental aneurysmal aortae compared with respective control aortae. Treatment with either HIF-1alpha inhibitor, beginning before or after PPE infusion, prevented enlargement of experimental aneurysms. Both HIF-1alpha inhibition regimens attenuated medial elastin degradation, smooth muscle cell depletion, and mural angiogenesis and the accumulation of macrophages, T cells, and B cells. Whereas mRNA levels for PHD1 and PHD2 were elevated in experimental aneurysmal aortae, pharmacologic inhibition of PHDs had limited effect on experimental aneurysm progression.CONCLUSIONS: Expression of HIF-1alpha and its target genes is increased in human and experimental AAAs. Treatment with HIF-1alpha inhibitors limits experimental AAA progression, with histologic evidence of attenuated mural leukocyte infiltration and angiogenesis. These findings underscore the potential significance of HIF-1alpha in aneurysm pathogenesis and as a target for pharmacologic suppression of AAA disease.

  View details for DOI 10.1016/j.jvs.2017.09.030

  View details for PubMedID 29242064

• Exercise Training Improves Ventilatory Efficiency in Patients With Small Abdominal Aortic Aneurysm: A Randomized Controlled Study Lima, R. M., Vainshelboim, B., Ganatra, R., Dalman, R., Chan, K., Myers, J. LIPPINCOTT WILLIAMS & WILKINS. 2017: 840

  View details for DOI 10.1249/01.mss.0000519259.98209.55

  View details for Web of Science ID 000415216000067

• Inhibition or deletion of angiotensin II type 1 receptor suppresses elastase-induced experimental abdominal aortic aneurysms. Journal of vascular surgery Xuan, H., Xu, B., Wang, W., Tanaka, H., Fujimura, N., Miyata, M., Michie, S. A., Dalman, R. L. 2017

  Abstract

  Angiotensin (Ang) II type 1 receptor (AT1) activation is essential for the development of exogenous Ang II-induced abdominal aortic aneurysms (AAAs) in hyperlipidemic animals. Experimental data derived from this modeling system, however, provide limited insight into the role of endogenous Ang II in aneurysm pathogenesis. Consequently, the potential translational value of AT1 inhibition in clinical AAA disease management remains incompletely understood on the basis of the existing literature.AAAs were created in wild-type (WT) and AT1a knockout (KO) mice by intra-aortic infusion of porcine pancreatic elastase (PPE). WT mice were treated with the AT1 receptor antagonist telmisartan, 10 mg/kg/d in chow, or the peroxisome proliferator-activated receptor γ (PPARγ) antagonist GW9662, 3 mg/kg/d through oral gavage, beginning 1 week before or 3 days after PPE infusion. Influences on aneurysm progression as well as mechanistic insights into AT1-mediated pathogenic processes were determined using noninvasive ultrasound imaging, histopathology, aortic gene expression profiling, and flow cytometric analysis.After PPE infusion, aortic enlargement was almost completely abrogated in AT1a KO mice compared with WT mice. As defined by a ≥50% increase in aortic diameter, no PPE-infused, AT1a KO mouse actually developed an AAA. On histologic evaluation, medial smooth muscle cellularity and elastic lamellae were preserved in AT1a KO mice compared with WT mice, with marked attenuation of mural angiogenesis and leukocyte infiltration. In WT mice, telmisartan administration effectively suppressed aneurysm pathogenesis after PPE infusion as well, regardless of whether treatment was initiated before or after aneurysm creation or continued for a limited or extended time. Telmisartan treatment was associated with reduced messenger RNA levels for CCL5 and matrix metalloproteinases 2 and 9 in aneurysmal aortae, with no apparent effect on PPARγ-regulated gene expression. Administration of the PPARγ antagonist GW9662 failed to "rescue" the aneurysm phenotype in telmisartan-treated, PPE-infused WT mice. Neither effector T-cell differentiation nor regulatory T-cell cellularity was affected by telmisartan treatment status.Telmisartan effectively suppresses the progression of elastase-induced AAAs without apparent effect on PPARγ activation or T-cell differentiation. These findings reinforce the critical importance of endogenous AT1 activation in experimental AAA pathogenesis and reinforce the translational potential of AT1 inhibition in medical aneurysm disease management.

  View details for DOI 10.1016/j.jvs.2016.12.110

  View details for PubMedID 28434702

• Dynamic Geometric Analysis of the Renal Arteries and Aorta following Complex Endovascular Aneurysm Repair. Annals of vascular surgery Ullery, B. W., Suh, G., Kim, J. J., Lee, J. T., Dalman, R. L., Cheng, C. P. 2017

  Abstract

  Aneurysm regression and target vessel patency during early and mid-term follow-up may be related to the effect of stent-graft configuration on the anatomy. We quantified geometry and remodeling of the renal arteries and aneurysm following fenestrated (F-) or snorkel/chimney (Sn-) endovascular aneurysm repair (EVAR).Twenty-nine patients (mean age, 76.8 ± 7.8 years) treated with F- or Sn-EVAR underwent computed tomography angiography at preop, postop, and follow-up. Three-dimensional geometric models of the aorta and renal arteries were constructed. Renal branch angle was defined relative to the plane orthogonal to the aorta. End-stent angle was defined as the angulation between the stent and native distal artery. Aortic volumes were computed for the whole aorta, lumen, and their difference (excluded lumen). Renal patency, reintervention, early mortality, postoperative renal impairment, and endoleak were reviewed.From preop to postop, F-renal branches angled upward, Sn-renal branches angled downward (P < 0.05), and Sn-renals exhibited increased end-stent angulation (12 ± 15°, P < 0.05). From postop to follow-up, branch angles did not change for either F- or Sn-renals, whereas F-renals exhibited increased end-stent angulation (5 ± 10°, P < 0.05). From preop to postop, whole aortic and excluded lumen volumes increased by 5 ± 14% and 74 ± 81%, whereas lumen volume decreased (39 ± 27%, P < 0.05). From postop to follow-up, whole aortic and excluded lumen volumes decreased similarly (P < 0.05), leaving the lumen volume unchanged. At median follow-up of 764 days (range, 7-1,653), primary renal stent patency was 94.1% and renal impairment occurred in 2 patients (6.7%).Although F- and Sn-EVAR resulted in significant, and opposite, changes to renal branch angle, only Sn-EVAR resulted in significant end-stent angulation increase. Longitudinal geometric analysis suggests that these anatomic alterations are primarily generated early as a consequence of the procedure itself and, although persistent, they show no evidence of continued significant change during the subsequent postoperative follow-up period.

  View details for DOI 10.1016/j.avsg.2016.12.005

  View details for PubMedID 28390918

• RGD targeting of human ferritin iron oxide nanoparticles enhances in vivo MRI of vascular inflammation and angiogenesis in experimental carotid disease and abdominal aortic aneurysm JOURNAL OF MAGNETIC RESONANCE IMAGING Kitagawa, T., Kosuge, H., Uchida, M., Iida, Y., Dalman, R. L., Douglas, T., McConnell, M. V. 2017; 45 (4): 1144-1153

  View details for DOI 10.1002/jmri.25459

  View details for Web of Science ID 000397489100020

• Evaluation of Cell Therapy on Exercise Performance and Limb Perfusion in Peripheral Artery Disease: The CCTRN Patients with Intermittent Claudication Injected with ALDH Bright Cells (PACE) Trial. Circulation Perin, E. C., Murphy, M. P., March, K. L., Bolli, R., Loughran, J., Yang, P. C., Leeper, N. J., Dalman, R. L., Alexander, J. Q., Henry, T. D., Traverse, J. H., Pepine, C. J., Anderson, R. D., Berceli, S., Willerson, J. T., Muthupillai, R., Gahremanpour, A. A., Raveendran, G., Velazquez, O. C., Hare, J. M., Schulman, I. H., Kasi, V. S., Hiatt, W. R., Ambale-Venkatesh, B., Lima, J. A., Taylor, D. A., Resende, M. M., Gee, A. P., Durett, A. G., Bloom, J., Richman, S., G'Sell, P., Williams, S., Khan, F., Ross, E. G., Santoso, M. R., Goldman, J., Leach, D., Handberg, E., Cheong, B. Y., Piece, N. A., Difede, D., Bruhn-Ding, B., Caldwell, E., Bettencourt, J., Lai, D., Piller, L. B., Simpson, L. M., Cohen, M., Sayre, S. L., Vojvodic, R. W., Moyé, L., Ebert, R. F., Simari, R. D., Hirsch, A. T. 2017

  Abstract

  Atherosclerotic peripheral artery disease affects 8% to 12% of Americans >65 years of age and is associated with a major decline in functional status, increased myocardial infarction and stroke rates, and increased risk of ischemic amputation. Current treatment strategies for claudication have limitations. PACE (Patients With Intermittent Claudication Injected With ALDH Bright Cells) is a National Heart, Lung, and Blood Institute-sponsored, randomized, double-blind, placebo-controlled, phase 2 exploratory clinical trial designed to assess the safety and efficacy of autologous bone marrow-derived aldehyde dehydrogenase bright (ALDHbr) cells in patients with peripheral artery disease and to explore associated claudication physiological mechanisms.All participants, randomized 1:1 to receive ALDHbr cells or placebo, underwent bone marrow aspiration and isolation of ALDHbr cells, followed by 10 injections into the thigh and calf of the index leg. The coprimary end points were change from baseline to 6 months in peak walking time (PWT), collateral count, peak hyperemic popliteal flow, and capillary perfusion measured by magnetic resonance imaging, as well as safety.A total of 82 patients with claudication and infrainguinal peripheral artery disease were randomized at 9 sites, of whom 78 had analyzable data (57 male, 21 female patients; mean age, 66±9 years). The mean±SEM differences in the change over 6 months between study groups for PWT (0.9±0.8 minutes; 95% confidence interval [CI] -0.6 to 2.5; P=0.238), collateral count (0.9±0.6 arteries; 95% CI, -0.2 to 2.1; P=0.116), peak hyperemic popliteal flow (0.0±0.4 mL/s; 95% CI, -0.8 to 0.8; P=0.978), and capillary perfusion (-0.2±0.6%; 95% CI, -1.3 to 0.9; P=0.752) were not significant. In addition, there were no significant differences for the secondary end points, including quality-of-life measures. There were no adverse safety outcomes. Correlative relationships between magnetic resonance imaging measures and PWT were not significant. A post hoc exploratory analysis suggested that ALDHbr cell administration might be associated with an increase in the number of collateral arteries (1.5±0.7; 95% CI, 0.1-2.9; P=0.047) in participants with completely occluded femoral arteries.ALDHbr cell administration did not improve PWT or magnetic resonance outcomes, and the changes in PWT were not associated with the anatomic or physiological magnetic resonance imaging end points. Future peripheral artery disease cell therapy investigational trial design may be informed by new anatomic and perfusion insights.URL: http://www.clinicaltrials.gov. Unique identifier: NCT01774097.

  View details for DOI 10.1161/CIRCULATIONAHA.116.025707

  View details for PubMedID 28209728

  View details for PubMedCentralID PMC5388585

• Natural history of gutter-related type Ia endoleaks after snorkel/chimney endovascular aneurysm repair. Journal of vascular surgery Ullery, B. W., Tran, K., Itoga, N. K., Dalman, R. L., Lee, J. T. 2017

  Abstract

  Alternative endovascular strategies using parallel or snorkel/chimney (chimney endovascular aneurysm repair [ch-EVAR]) techniques have been developed to address the lack of widespread availability and manufacturing limitations with branched/fenestrated aortic devices for the treatment of complex abdominal aortic aneurysms. Despite high technical success and midterm patency of snorkel stent configurations, concerns remain regarding the perceived increased incidence of early gutter-related type Ia endoleaks. We aimed to evaluate the incidence and natural history of gutter-related type Ia endoleaks following ch-EVAR.Review of medical records and available imaging studies, including completion angiography and serial computed tomographic angiography, was performed for all patients undergoing ch-EVAR at our institution between September 2009 and January 2015. Only procedures involving ≥1 renal artery with or without visceral snorkel stents were included. Primary outcomes of the study were presence and persistence or resolution of early gutter-related type Ia endoleak. Secondary outcomes included aneurysm sac shrinkage and need for secondary intervention related to the presence of type Ia gutter endoleak.Sixty patients (mean age, 75.8 ± 7.6 years; male, 70.0%) underwent ch-EVAR with a total of 111 snorkel stents (97 renal [33 bilateral renal], 12 superior mesenteric artery, 2 celiac). A mean of 1.9 ± 0.6 snorkel stents were placed per patient. Early gutter-related type Ia endoleaks were noted on 30.0% (n = 18) of initial postoperative imaging studies. Follow-up imaging revealed spontaneous resolution of these gutter endoleaks in 44.3%, 65.2%, and 88.4% of patients at 6, 12, and 18 months postprocedure, respectively. Long-term anticoagulation, degree of oversizing, stent type and diameter, and other clinical/anatomic variables were not significantly associated with presence of gutter endoleaks. Two patients (3.3%) required secondary intervention related to persistent gutter endoleak. At a mean radiologic follow-up of 20.9 months, no difference in mean aneurysm sac size change was observed between those with or without early type Ia gutter endoleak (-6.1 ± 10.0 mm vs -4.9 ± 11.5 mm; P = .23).Gutter-related type Ia endoleaks represent a relatively frequent early occurrence after ch-EVAR, but appears to resolve spontaneously in the majority of cases during early to midterm follow-up. Given that few ch-EVAR patients require reintervention related to gutter endoleaks and the presence of such endoleak did not correlate to increased risk for aneurysm sac growth, its natural history may be more benign than originally expected.

  View details for DOI 10.1016/j.jvs.2016.10.085

  View details for PubMedID 28189356

• Challenges and opportunities in limiting abdominal aortic aneurysm growth JOURNAL OF VASCULAR SURGERY Golledge, J., Norman, P. E., Murphy, M. P., Dalman, R. L. 2017; 65 (1): 225-233

  Abstract

  This review describes ongoing efforts to develop a medical therapy to limit abdominal aortic aneurysm (AAA) growth.Data from animal model studies, human investigations, and clinical trials are described.Studies in rodent models and human samples have suggested a number of potential targets for slowing or halting AAA growth. A number of clinical trials are now examining the value of medications targeting some of the pathways identified. These trials have a number of challenges, including identifying medications safe to use in older patients with multiple comorbidities, developing accurate outcome assessments, and minimizing the dropout of patients during the trials. Three recent trials have reported no benefit of the antibiotic doxycycline, a mast cell inhibitor, an angiotensin-converting enzyme inhibitor, or a calcium channel blocker in limiting AAA growth. A number of other trials examining angiotensin receptor blockers, cyclosporine, and an antiplatelet agent are currently underway.Further refinement of drug discovery pathways and testing paradigms are likely needed to develop effective nonsurgical therapies for AAA.

  View details for DOI 10.1016/j.jvs.2016.08.003

  View details for Web of Science ID 000390045100061

  View details for PubMedID 27641464

• Management and outcomes of symptomatic abdominal aortic aneurysms during the past 20 years. Journal of vascular surgery Chandra, V., Trang, K., Virgin-Downey, W., Tran, K., Harris, E. J., Dalman, R. L., Lee, J. T., Mell, M. W. 2017; 66 (6): 1679–85

  Abstract

  We compared the management of patients with symptomatic, unruptured abdominal aortic aneurysms (AAAs) treated at a tertiary care center between two decades. This 20-year period encapsulated a shift in surgical approach to aortic aneurysms from primarily open to primarily endovascular, and we sought to determine the effect of this shift in the evaluation, treatment, and clinical outcomes of patients with symptomatic AAA.We reviewed 1429 consecutive patients with unruptured AAAs treated at a tertiary care hospital by six staff surgeons between 1995 and 2004 (era 1) and between 2005 and 2014 (era 2). Of those patients, 160 (11%) were symptomatic from their aneurysm and were included in our study. Patient demographics, operative approach, and outcomes were analyzed and compared for each period.Era 1 included 75 patients (71% men; average age, 73.1 ± 10.0 years) treated for symptomatic AAA (91.9% infrarenal, 4.0% juxtarenal, and 4.0% pararenal); of these, 68% were treated with open repair and 32.0% were treated with an endovascular repair. Perioperative mortality during this period was 5.3% (7.8% for the open cohort and 0% for the endovascular cohort). Era 2 included 85 patients (72.9% men; average age 72.0 ± 9.5 years) treated for symptomatic AAA (90.1% infrarenal, 7.5% juxtarenal, and 2.4% pararenal); of these, 29% were treated open and 71% underwent endovascular repair. Perioperative mortality was 5.9% (8.0% for the open cohort and 5.0% for the endovascular cohort). Era 2 had a significantly higher rate of endovascular repair compared with era 1 (71% vs 32%; P < .0001) and a trend toward decreased long-term mortality. The length of stay for era 2 was significantly reduced compared with era 1 (4 days vs 6 days; P = .005).To our knowledge, this is the largest single-institution cohort of symptomatic AAAs, which comprise 10% to 11% of overall aneurysms. As expected, we found a significant shift over time in the approach to these patients from a primarily open to a primarily endovascular technique. The modern era was also associated with decreased lengths of stay and fewer gastrointestinal and wound complications but no significant differences in overall perioperative mortality.

  View details for DOI 10.1016/j.jvs.2017.04.033

  View details for PubMedID 28619644

• Incidence and prognostic factors related to major adverse cerebrovascular events in patients with complex aortic diseases treated by the chimney technique. Journal of vascular surgery Bosiers, M. J., Tran, K., Lee, J. T., Donas, K. P., Veith, F. J., Torsello, G., Pecoraro, F., Stavroulakis, K. 2017

  Abstract

  Endovascular aneurysm repair (EVAR) with the chimney technique (ch-EVAR) has been used for the treatment of aortic aneurysms as an alternative approach to fenestrated endografting or open repair. Nonetheless, the need for an upper extremity arterial access may contribute to a higher risk for periprocedural cerebrovascular events. This study reports on the perioperative cerebral and major adverse cardiac and cerebrovascular events (MACCE) after ch-EVAR.The PERICLES registry (PERformance of the chImney technique for the treatment of Complex aortic pathoLogiES) is an international, retrospective multicenter study evaluating the performance of ch-EVAR for the treatment of complex aortic pathologies. For the purpose of the current analysis, 425 patients treated by ch-EVAR between 2008 and 2014 were included. The primary outcome of this analysis was the incidence of procedure related cerebrovascular events defined as transient ischemic attack or stroke. The secondary end point was in-hospital MACCE, including acute coronary syndrome, stroke, and death of any cause.The incidence of clinical relevant cerebrovascular events was 1.9% (8/425). A postoperative transient ischemic attack was observed in four patients (0.95%) and a stroke in additional four (0.95%). Three patients died during the hospital stay secondary to sequelae from postoperative stroke. A prior history of stroke/transient ischemic attack, atrial fibrillation, previous carotid revascularization, or known carotid artery disease did not significantly increase the risk for adverse neurologic events. The overall MACCE rate amounted to 8.5% (36/425). Logistic regression analysis revealed that the use of bilateral upper extremity access (odds ratio [OR], 2.79; 95% confidence interval [CI], 1.04-7.45]), aneurysm rupture (OR, 5.33; 95% CI, 1.74-16.33), and a prolonged operation time (>290 minutes; OR, 1.005; 95% CI, 1.001-1.008) were associated with a significantly increased risk for MACCE.This analysis demonstrates that ch-EVAR is associated with a relatively low rate of cerebrovascular events. However, a postoperative stroke is associated with increased mortality. Ruptured aneurysms, bilateral upper extremity access as in case of multiple chimney graft placement, and longer operative times were identified as independent risk factors for MACCE.

  View details for DOI 10.1016/j.jvs.2017.08.079

  View details for PubMedID 29103932

• Predictive models for mortality after ruptured aortic aneurysm repair do not predict futility and are not useful for clinical decision making JOURNAL OF VASCULAR SURGERY Thompson, P. C., Dalman, R. L., Harris, E. J., Chandra, V., Lee, J. T., Mell, M. W. 2016; 64 (6): 1617-1622

  Abstract

  The clinical decision-making utility of scoring algorithms for predicting mortality after ruptured abdominal aortic aneurysms (rAAAs) remains unknown. We sought to determine the clinical utility of the algorithms compared with our clinical decision making and outcomes for management of rAAA during a 10-year period.Patients admitted with a diagnosis rAAA at a large university hospital were identified from 2005 to 2014. The Glasgow Aneurysm Score, Hardman Index, Vancouver Score, Edinburgh Ruptured Aneurysm Score, University of Washington Ruptured Aneurysm Score, Vascular Study Group of New England rAAA Risk Score, and the Artificial Neural Network Score were analyzed for accuracy in predicting mortality. Among patients quantified into the highest-risk group (predicted mortality >80%-85%), we compared the predicted with the actual outcome to determine how well these scores predicted futility.The cohort comprised 64 patients. Of those, 24 (38%) underwent open repair, 36 (56%) underwent endovascular repair, and 4 (6%) received only comfort care. Overall mortality was 30% (open repair, 26%; endovascular repair, 24%; no repair, 100%). As assessed by the scoring systems, 5% to 35% of patients were categorized as high-mortality risk. Intersystem agreement was poor, with κ values ranging from 0.06 to 0.79. Actual mortality was lower than the predicted mortality (50%-70% vs 78%-100%) for all scoring systems, with each scoring system overestimating mortality by 10% to 50%. Mortality rates for patients not designated into the high-risk cohort were dramatically lower, ranging from 7% to 29%. Futility, defined as 100% mortality, was predicted in five of 63 patients with the Hardman Index and in two of 63 of the University of Washington score. Of these, surgery was not offered to one of five and one of two patients, respectively. If one of these two models were used to withhold operative intervention, the mortality of these patients would have been 100%. The actual mortality for these patients was 60% and 50%, respectively.Clinical algorithms for predicting mortality after rAAA were not useful for predicting futility. Most patients with rAAA were not classified in the highest-risk group by the clinical decision models. Among patients identified as highest risk, predicted mortality was overestimated compared with actual mortality. The data from this study support the limited value to surgeons of the currently published algorithms.

  View details for DOI 10.1016/j.jvs.2016.07.121

  View details for Web of Science ID 000390044000011

  View details for PubMedID 27871490

• The use of machine learning for the identification of peripheral artery disease and future mortality risk. Journal of vascular surgery Ross, E. G., Shah, N. H., Dalman, R. L., Nead, K. T., Cooke, J. P., Leeper, N. J. 2016; 64 (5): 1515-1522 e3

  Abstract

  A key aspect of the precision medicine effort is the development of informatics tools that can analyze and interpret "big data" sets in an automated and adaptive fashion while providing accurate and actionable clinical information. The aims of this study were to develop machine learning algorithms for the identification of disease and the prognostication of mortality risk and to determine whether such models perform better than classical statistical analyses.Focusing on peripheral artery disease (PAD), patient data were derived from a prospective, observational study of 1755 patients who presented for elective coronary angiography. We employed multiple supervised machine learning algorithms and used diverse clinical, demographic, imaging, and genomic information in a hypothesis-free manner to build models that could identify patients with PAD and predict future mortality. Comparison was made to standard stepwise linear regression models.Our machine-learned models outperformed stepwise logistic regression models both for the identification of patients with PAD (area under the curve, 0.87 vs 0.76, respectively; P = .03) and for the prediction of future mortality (area under the curve, 0.76 vs 0.65, respectively; P = .10). Both machine-learned models were markedly better calibrated than the stepwise logistic regression models, thus providing more accurate disease and mortality risk estimates.Machine learning approaches can produce more accurate disease classification and prediction models. These tools may prove clinically useful for the automated identification of patients with highly morbid diseases for which aggressive risk factor management can improve outcomes.

  View details for DOI 10.1016/j.jvs.2016.04.026

  View details for PubMedID 27266594

  View details for PubMedCentralID PMC5079774

• RGD targeting of human ferritin iron oxide nanoparticles enhances in vivo MRI of vascular inflammation and angiogenesis in experimental carotid disease and abdominal aortic aneurysm. Journal of magnetic resonance imaging : JMRI Kitagawa, T., Kosuge, H., Uchida, M., Iida, Y., Dalman, R. L., Douglas, T., McConnell, M. V. 2016

  Abstract

  To evaluate Arg-Gly-Asp (RGD)-conjugated human ferritin (HFn) iron oxide nanoparticles for in vivo magnetic resonance imaging (MRI) of vascular inflammation and angiogenesis in experimental carotid disease and abdominal aortic aneurysm (AAA).HFn was genetically engineered to express the RGD peptide and Fe3 O4 nanoparticles were chemically synthesized inside the engineered HFn (RGD-HFn). Macrophage-rich left carotid lesions were induced by ligation in FVB mice made hyperlipidemic and diabetic (n = 14), with the contralateral right carotid serving as control. Murine AAAs were created by continuous angiotensin II infusion in ApoE-deficient mice (n = 12), while control mice underwent saline infusion (n = 8). All mice were imaged before and after intravenous injection with either RGD-HFn-Fe3 O4 or HFn-Fe3 O4 using a gradient-echo sequence on a whole-body 3T clinical scanner, followed by histological analysis. The nanoparticle accumulation was assessed by the extent of T2*-induced carotid lumen reduction (% lumen loss) or aortic T2*-weighted signal intensity reduction (% SI [signal intensity] loss).RGD-HFn-Fe3 O4 was taken up more than HFn-Fe3 O4 in both the ligated left carotid arteries (% lumen loss; 69 ± 9% vs. 36 ± 7%, P = 0.01) and AAAs (% SI loss; 47 ± 6% vs. 20 ± 5%, P = 0.01). The AAA % SI loss correlated positively with AAA size (r = 0.89, P < 0.001). Histology confirmed the greater accumulation and colocalization of RGD-HFn-Fe3 O4 to both vascular macrophages and endothelial cells.RGD-HFn-Fe3 O4 enhances in vivo MRI by targeting both vascular inflammation and angiogenesis, and provides a promising translatable MRI approach to detect high-risk atherosclerotic and aneurysmal vascular diseases.1 J. Magn. Reson. Imaging 2016.

  View details for DOI 10.1002/jmri.25459

  View details for PubMedID 27689830

• Arterial cutdown reduces complications after brachial access for peripheral vascular intervention JOURNAL OF VASCULAR SURGERY Kret, M. R., Dalman, R. L., Kalish, J., Mell, M. 2016; 64 (1): 149-154

  Abstract

  Factors influencing risk for brachial access site complications after peripheral vascular intervention are poorly understood. We queried the Society for Vascular Surgery Vascular Quality Initiative to identify unique demographic and technical risks for such complications.The Vascular Quality Initiative peripheral vascular intervention data files from years 2010 to 2014 were analyzed to compare puncture site complication rates and associations encountered with either brachial or femoral arterial access for peripheral vascular intervention. Procedures requiring multiple access sites were excluded. Complications were defined as wound hematoma or access vessel stenosis/occlusion. Univariate and hierarchical logistic regression was used to identify independent factors associated with site complications after brachial access.Of 44,634 eligible peripheral vascular intervention procedures, 732 (1.6%) were performed through brachial access. Brachial access was associated with an increased complication rate compared with femoral access (9.0% vs 3.3%; P < .001), including more hematomas (7.2% vs 3.0%; P < .001) and access site stenosis/occlusion (2.1% vs 0.4%; P < .001). On univariate analysis, factors associated with brachial access complications included age, female gender, and sheath size. Complications occurred less frequently after arterial cutdown (4.1%) compared with either ultrasound-guided (11.8%) or fluoroscopically guided percutaneous access (7.3%; P = .07 across all variables). Neither surgeons' overall peripheral vascular intervention experience nor prior experience with brachial access predicted likelihood of adverse events. By multivariate analysis, male gender (odds ratio [OR], 0.48; 95% confidence interval [CI], 0.28-0.84; P < .01) and arterial cutdown (OR, 0.25; 95% CI, 0.07-0.87; P = .04) were associated with significantly decreased risk for access complications. Larger sheath sizes (>5F) were associated with increased risk of complications (OR, 2.19; 95% CI, 1.07-4.49; P = .03).Brachial access for peripheral vascular intervention carries significantly increased risks for access site occlusion or hematoma formation. Arterial cutdown and smaller sheath diameters are associated with lower complication rates and thus should be considered when arm access is required.

  View details for DOI 10.1016/j.jvs.2016.02.019

  View details for Web of Science ID 000378562900021

  View details for PubMedID 27021376

• Metformin treatment status and abdominal aortic aneurysm disease progression JOURNAL OF VASCULAR SURGERY Fujimura, N., Xiong, J., Kettler, E. B., Xuan, H., Glover, K. J., Mell, M. W., Xu, B., Dalman, R. L. 2016; 64 (1): 46-?

  Abstract

  In population-based studies performed on multiple continents during the past two decades, diabetes mellitus has been negatively associated with the prevalence and progression of abdominal aortic aneurysm (AAA) disease. We investigated the possibility that metformin, the primary oral hypoglycemic agent in use worldwide, may influence the progression of AAA disease.Preoperative AAA patients with diabetes were identified from an institutional database. After tabulation of individual cardiovascular and demographic risk factors and prescription drug regimens, odds ratios for categorical influences on annual AAA enlargement were calculated through nominal logistical regression. Experimental AAA modeling experiments were subsequently performed in normoglycemic mice to validate the database-derived observations as well as to suggest potential mechanisms of metformin-mediated aneurysm suppression.Fifty-eight patients met criteria for study inclusion. Of 11 distinct classes of medication considered, only metformin use was negatively associated with AAA enlargement. This association remained significant after controlling for gender, age, cigarette smoking status, and obesity. The median enlargement rate in AAA patients not taking oral diabetic medication was 1.5 mm/y; by nominal logistic regression, metformin, hyperlipidemia, and age ≥70 years were associated with below-median enlargement, whereas sulfonylurea therapy, initial aortic diameter ≥40 mm, and statin use were associated with above-median enlargement. In experimental modeling, metformin dramatically suppressed the formation and progression, with medial elastin and smooth muscle preservation and reduced aortic mural macrophage, CD8 T cell, and neovessel density.Epidemiologic evidence of AAA suppression in diabetes may be attributable to concurrent therapy with the oral hypoglycemic agent metformin.

  View details for DOI 10.1016/j.jvs.2016.02.020

  View details for Web of Science ID 000378562900009

  View details for PubMedID 27106243

  View details for PubMedCentralID PMC4925242

• Three-Dimensional Modeling Analysis of Visceral Arteries and Kidneys during Respiration. Annals of vascular surgery Suh, G., Choi, G., Herfkens, R. J., Dalman, R. L., Cheng, C. P. 2016; 34: 250-260

  Abstract

  Visceral arteries are commonly involved in endovascular repair of complex abdominal aortic aneurysms (AAAs). To improve repair techniques and reduce long-term complications involving visceral arteries, it is crucial to understand in vivo arterial geometry and the deformations due to visceral organ movement with respiration. This study quantifies deformation of the celiac, superior mesenteric (SMA), and renal arteries during respiration and correlates the deformations with diaphragmatic excursion.Sixteen patients with small AAAs underwent magnetic resonance angiography during inspiratory and expiratory breathholds. From geometric models of the aorta and visceral arteries, vessel length, branch angle, curvature, and positions were computed, along with degree of diaphragmatic excursion as indicated by kidney translation.From inspiration to expiration, the celiac artery exhibited axial shortening of 4.8 ± 6.4% (P < 0.001) and a mean curvature increase of 0.03 ± 0.02 mm(-1), greater than other visceral arteries (P < 0.01). With expiration, the SMA, left and right renal arteries (LRA and RRA) angled upward by -9.8 ± 6.4°, -6.4 ± 6.4°, and -5.2 ± 5.0°, respectively (P < 0.005). All vessels translated superiorly (P < 0.0005) and posteriorly (P < 0.01), and the SMA translated rightward additionally (P < 0.005). The left and right kidneys translated by 22 ± 9 mm and 21 ± 9 mm, mostly superiorly (P < 0.001). Translations of all visceral arteries were moderately correlated to the right kidney (R > 0.50). Correlation of the LRA with the left kidney was greater than that of the RRA with the right kidney.The celiac artery exhibited less branch angle change, and greater axial and curvature deformations than the other visceral arteries, due to the vicinity to the liver and influence of the median arcuate ligament. Correlation between visceral arteries and kidney translations revealed that diaphragmatic excursion affects vessel mobility. Weaker correlation of the RRA to the right kidney indicates mechanical shielding from the inferior vena cava.

  View details for DOI 10.1016/j.avsg.2016.04.004

  View details for PubMedID 27116907

  View details for PubMedCentralID PMC4930742

• Comparative geometric analysis of renal artery anatomy before and after fenestrated or snorkel/chimney endovascular aneurysm repair. Journal of vascular surgery Ullery, B. W., Suh, G., Lee, J. T., Liu, B., Stineman, R., Dalman, R. L., Cheng, C. P. 2016; 63 (4): 922-929

  Abstract

  The durability of stent grafts may be related to how procedures and devices alter native anatomy. We aimed to quantify and compare renal artery geometry before and after fenestrated (F-) or snorkel/chimney (Sn-) endovascular aneurysm repair (EVAR).Forty patients (75 ± 6 years) underwent computed tomographic angiography before and after F-EVAR (n = 21) or Sn-EVAR (n = 19), with a total of 72 renal artery stents. Renal artery geometry was quantified using three-dimensional model-based centerline extraction. The stented length was computed from the vessel origin to the stent end. The branch angle was computed relative to the orthogonal configuration with respect to the aorta. The end-stent angle was computed relative to the distal native renal artery. Peak curvature was defined as the inverse of the radius of the circumscribed circle at the highest curvature within the proximal portion from the origin to the stent end and the distal portion from the stent end to the first renal artery bifurcation.Sn-renals had greater stented length compared to F-renals (P < .05). From the pre- to the postoperative period, the origins of the Sn-left renal artery and right renal artery (RRA) angled increasingly downward by 21 ± 19° and 13 ± 17°, respectively (P < .005). The F-left renal artery and RRA angled upward by 25 ± 15° and 14 ± 15°, respectively (P < .005). From the pre- to the postoperative period, the end-stent angle of the Sn-RRA increased by 17 ± 12° (P < .00001), with greater magnitude change compared to the F-RRA (P < .0005). Peak curvature increased in distal Sn-RRAs by .02 ± .03 mm(-1) (P < .05). Acute renal failure occurred in 12.5% of patients, although none required dialysis following either F- and Sn-EVAR. Renal stent patency was 97.2% at mean follow-up of 13.7 months. Three type IA endoleaks were identified, prompting one secondary procedure, with the remainder resolving at 6-month follow-up. One renal artery reintervention was performed due to a compressed left renal stent in an asymptomatic patient.Stented renal arteries were angled more inferiorly after Sn-EVAR and more superiorly after F-EVAR due to stent configuration. Sn-EVAR induced significantly greater angle change at the stent end and curvature change distal to the stent compared to F-EVAR, although no difference in patency was noted in this small series with relatively short follow-up. Sn-RRAs exhibited greater end-stent angle change from the pre- to the postoperative period as compared to the F-RRA. These differences may exert differential effects on long-term renal artery patency, integrity, and renal function following complex EVAR for juxta- or pararenal abdominal aortic aneurysms.

  View details for DOI 10.1016/j.jvs.2015.10.091

  View details for PubMedID 26755068

• Heme Oxygenase-1 Expression Affects Murine Abdominal Aortic Aneurysm Progression. PloS one Azuma, J., Wong, R. J., Morisawa, T., Hsu, M., Maegdefessel, L., Zhao, H., Kalish, F., Kayama, Y., Wallenstein, M. B., Deng, A. C., Spin, J. M., Stevenson, D. K., Dalman, R. L., Tsao, P. S. 2016; 11 (2)

  Abstract

  Heme oxygenase-1 (HO-1), the rate-limiting enzyme in heme degradation, is a cytoprotective enzyme upregulated in the vasculature by increased flow and inflammatory stimuli. Human genetic data suggest that a diminished HO-1 expression may predispose one to abdominal aortic aneurysm (AAA) development. In addition, heme is known to strongly induce HO-1 expression. Utilizing the porcine pancreatic elastase (PPE) model of AAA induction in HO-1 heterozygous (HO-1+/-, HO-1 Het) mice, we found that a deficiency in HO-1 leads to augmented AAA development. Peritoneal macrophages from HO-1+/- mice showed increased gene expression of pro-inflammatory cytokines, including MCP-1, TNF-alpha, IL-1-beta, and IL-6, but decreased expression of anti-inflammatory cytokines IL-10 and TGF-beta. Furthermore, treatment with heme returned AAA progression in HO-1 Het mice to a wild-type profile. Using a second murine AAA model (Ang II-ApoE-/-), we showed that low doses of the HMG-CoA reductase inhibitor rosuvastatin can induce HO-1 expression in aortic tissue and suppress AAA progression in the absence of lipid lowering. Our results support those studies that suggest that pleiotropic statin effects might be beneficial in AAA, possibly through the upregulation of HO-1. Specific targeted therapies designed to induce HO-1 could become an adjunctive therapeutic strategy for the prevention of AAA disease.

  View details for DOI 10.1371/journal.pone.0149288

  View details for PubMedID 26894432

  View details for PubMedCentralID PMC4760983

• Erratum to: 'TElmisartan in the management of abDominal aortic aneurYsm (TEDY): The study protocol for a randomized controlled trial'. Trials Morris, D. R., Cunningham, M. A., Ahimastos, A. A., Kingwell, B. A., Pappas, E., Bourke, M., Reid, C. M., Stijnen, T., Dalman, R. L., Aalami, O. O., Lindeman, J. H., Norman, P. E., Walker, P. J., Fitridge, R., Bourke, B., Dear, A. E., Pinchbeck, J., Jaeggi, R., Golledge, J. 2016; 17 (1): 43-?

  View details for DOI 10.1186/s13063-016-1183-x

  View details for PubMedID 26791257

• Association of an Endovascular-First Protocol for Ruptured Abdominal Aortic Aneurysms With Survival and Discharge Disposition JAMA SURGERY Ullery, B. W., Tran, K., Chandra, V., Mell, M. W., Harris, E. J., Dalman, R. L., Lee, J. T. 2015; 150 (11): 1058-1065

  Abstract

  Mortality after an open surgical repair of a ruptured abdominal aortic aneurysm (rAAA) remains high. The role and clinical benefit of ruptured endovascular aneurysm repair (rEVAR) have yet to be fully elucidated.To evaluate the effect of an endovascular-first protocol for patients with an rAAA on perioperative mortality and associated early clinical outcomes.Retrospective review of a consecutive series of patients presenting with an rAAA before (1997-2006) and after (2007-2014) implementation of an endovascular-first treatment strategy (ie, protocol) at an academic medical center.Early mortality, perioperative morbidity, discharge disposition, and overall survival.A total of 88 patients with an rAAA were included in the analysis, including 46 patients in the preprotocol group (87.0% underwent an open repair and 13.0% underwent an rEVAR) and 42 patients in the intention-to-treat postprotocol group (33.3% underwent an open repair and 66.7% underwent an rEVAR; P = .001). Baseline demographics were similar between groups. Postprotocol patients died significantly less often at 30 days (14.3% vs 32.6%; P = .03), had a decreased incidence of major complications (45.0% vs 71.8%; P = .02), and had a greater likelihood of discharge to home (69.2% vs 42.1%; P = .04) after rAAA repair compared with preprotocol patients. Kaplan-Meier analysis demonstrated significantly greater long-term survival in the postprotocol period (log-rank P = .002). One-, 3-, and 5-year survival rates were 50.0%, 45.7%, and 39.1% for open repair, respectively, and 61.9%, 42.9%, and 23.8% for rEVAR, respectively.Implementation of a contemporary endovascular-first protocol for the treatment of an rAAA is associated with decreased perioperative morbidity and mortality, a higher likelihood of discharge to home, and improved long-term survival. Patients with an rAAA and appropriate anatomy should be offered endovascular repair as first-line treatment at experienced vascular centers.

  View details for DOI 10.1001/jamasurg.2015.1861

  View details for Web of Science ID 000367987100011

• Abdominal Aortic Hemodynamics in Intermittent Claudication Patients at Rest and during Dynamic Pedaling Exercise ANNALS OF VASCULAR SURGERY Cheng, C. P., Taylor, C. A., Dalman, R. L. 2015; 29 (8): 1516-1523

  View details for DOI 10.1016/j.avsg.2015.06.089

  View details for Web of Science ID 000363475300006

  View details for PubMedID 26315797

• Snorkel/chimney and fenestrated endografts for complex abdominal aortic aneurysms. journal of cardiovascular surgery Ullery, B. W., Lee, J. T., Dalman, R. L. 2015; 56 (5): 707-717

  Abstract

  Complex endovascular aneurysm repair (EVAR) involves extension of the proximal aortic seal zone with preservation of branch vessel patency, thereby expanding the applicability of endografting from the infrarenal to the suprarenal aorta. Snorkel/chimney (Sn-EVAR) and fenestrated EVAR (f-EVAR) serve as the two most commonly utilized advanced endovascular techniques to combat hostile proximal neck anatomy. The purpose of this article is to describe the principles and evolution of these advanced endovascular strategies, technical considerations, and results of sn- and f-EVAR in the management of challenging neck anatomy in abdominal aortic aneurysm disease.

  View details for PubMedID 25800354

• Impact of Renal Artery Angulation on Procedure Efficiency During Fenestrated and Snorkel/Chimney Endovascular Aneurysm Repair JOURNAL OF ENDOVASCULAR THERAPY Ullery, B. W., Chandra, V., Dalman, R. L., Lee, J. T. 2015; 22 (4): 594-602

  Abstract

  To determine the impact of renal artery angulation on time to successful renal artery cannulation and procedure efficiency during fenestrated and snorkel/chimney endovascular aneurysm repair (EVAR).The imaging and procedure logs of 77 patients (mean age 74.2 years; 63 men) who underwent complex EVAR (24 fenestrated, 53 snorkel/chimney) from 2009 to 2013 were reviewed. Renal artery angulation was measured on preoperative computed tomographic angiography scans. Time to renal artery cannulation was retrieved from the EVAR procedure logs and compared to preoperative renal artery angulation and other metrics of procedure efficiency (eg, procedure time, fluoroscopy time, blood loss, etc). In all, 111 renal arteries were available for renal artery angulation measurement (39 fenestrated, 72 snorkel/chimney); 22 renal cannulations were inappropriate for the comparative analyses due to concomitant visceral artery stenting (n=15), combined procedures (n=6), or unsuccessful cannulation (n=1).For patients undergoing fenestrated EVAR, mean renal artery angulation was -28°±21° (range +37° to -60°), not significantly different (p=0.66) from patients receiving snorkel/chimney grafts (mean -30°±19°, range +22° to -65°). Comparative analysis using median renal artery angulation (-30° for both groups) demonstrated that renal artery cannulation during fenestrated EVAR was performed significantly faster in arteries with less downward (≥ -30°) angulation (16.0 vs 32.8 minutes, p=0.04), whereas cannulation in snorkel/chimneys was faster in arteries with greater downward (< -30°) angulation (10.9 vs 17.3 minutes, p=0.05). Fenestrated EVAR cases involving less downward (≥ -30°) renal artery angulation were also associated with shorter overall procedure time (187.7 vs 246.2 minutes, p=0.01) and decreased fluoroscopy time (70.3 vs 98.2 minutes, p=0.04). Immediate renal function decline, procedural complications, and postoperative issues were not associated with renal artery angulation.Procedural efficiency may be optimized by considering renal artery angulation as one of several objective variables used in the selection of an appropriate endovascular strategy. The fenestrated approach is more efficient with less downward angulation to the renal arteries, while the snorkel/chimney strategy is facilitated by more downward renal artery angulation.

  View details for DOI 10.1177/1526602815590119

  View details for Web of Science ID 000358119200019

• CCR2 inhibition sequesters multiple subsets of leukocytes in the bone marrow SCIENTIFIC REPORTS Fujimura, N., Xu, B., Dalman, J., Deng, H., Aoyama, K., Dalman, R. L. 2015; 5

  View details for DOI 10.1038/srep11664

  View details for Web of Science ID 000358419600001

• TElmisartan in the management of abDominal aortic aneurYsm (TEDY): The study protocol for a randomized controlled trial TRIALS Morris, D. R., Cunningham, M. A., Ahimastos, A. A., Kingwell, B. A., Pappas, E., Bourke, M., Reid, C. M., Stijnen, T., Dalman, R. L., Aalami, O. O., Lindeman, J. H., Norman, P. E., Walker, P. J., Fitridge, R., Bourke, B., Dear, A. E., Pinchbeck, J., Jaeggi, R., Golledge, J. 2015; 16

  View details for DOI 10.1186/s13063-015-0793-z

  View details for Web of Science ID 000356847800001

  View details for PubMedID 26081587

• Safety and efficacy of antiplatelet/anticoagulation regimens after Viabahn stent graft treatment for femoropopliteal occlusive disease JOURNAL OF VASCULAR SURGERY Ullery, B. W., Tran, K., Itoga, N., Casey, K., Dalman, R. L., Lee, J. T. 2015; 61 (6): 1479-1488

  Abstract

  We aimed to determine the safety and efficacy of antiplatelet/anticoagulation regimens after placement of Viabahn stent graft (W. L. Gore & Associates, Flagstaff, Ariz) for the treatment of femoropopliteal occlusive disease.Clinical, angiographic, and procedural data for patients undergoing endovascular treatment of femoropopliteal occlusive disease using Viabahn covered stent grafts at a single institution between 2006 and 2013 were retrospectively reviewed. Graft patency and freedom from thrombolysis, major adverse limb event, and reintervention were determined by Kaplan-Meier analysis. The influence of relevant variables on clinical outcome was determined through univariate and multivariate Cox proportional hazards analyses.Viabahn stent grafts were placed in a total of 91 limbs in 61 patients (66% men; mean age, 69 ± 12 years) during the study period. Indication for intervention was either claudication (n = 59) or critical limb ischemia (n = 32), with the majority (70%) classified as TransAtlantic Inter-Society Consensus II C (n = 33) or D (n = 31) lesions. Mean follow-up was 38.3 months (range, 1-91 months). Postprocedural pharmacologic regimens included aspirin, clopidogrel, and warfarin (47%); indefinite aspirin and clopidogrel (46%); or aspirin and temporary clopidogrel (7%). Primary and secondary patency rates were 60%, 44%, and 36% and 95%, 82%, and 74% at 1 year, 3 years, and 5 years, respectively. Kaplan-Meier analysis demonstrated more aggressive antiplatelet/anticoagulation regimens to be associated with improved primary patency and freedom from reintervention. Cox proportional hazards analysis demonstrated TransAtlantic Inter-Society Consensus II D lesions, tobacco use, coronary artery disease, and smaller stent diameter to be independent risk factors for stent graft failure. Bleeding events were limited to those in the aspirin, clopidogrel, and warfarin group (11.6% [n = 5]; P = .052), although the majority of these events were not life-threatening, and only two cases required blood transfusion.Increasingly aggressive antithrombotic regimens after Viabahn stent graft placement trended toward improved overall clinical outcomes, although the marginal patency benefit observed with the addition of warfarin to dual antiplatelet therapy was tempered by an observed increased risk of bleeding complications. Longer term follow-up and multicenter studies are needed to further define optimal type and duration of antithrombotic therapy after endovascular peripheral interventions.

  View details for DOI 10.1016/j.jvs.2014.12.062

  View details for Web of Science ID 000355018500013

  View details for PubMedID 25704407

• Safety and efficacy of antiplatelet/anticoagulation regimens after Viabahn stent graft treatment for femoropopliteal occlusive disease. Journal of vascular surgery Ullery, B. W., Tran, K., Itoga, N., Casey, K., Dalman, R. L., Lee, J. T. 2015; 61 (6): 1479-1488

  Abstract

  We aimed to determine the safety and efficacy of antiplatelet/anticoagulation regimens after placement of Viabahn stent graft (W. L. Gore & Associates, Flagstaff, Ariz) for the treatment of femoropopliteal occlusive disease.Clinical, angiographic, and procedural data for patients undergoing endovascular treatment of femoropopliteal occlusive disease using Viabahn covered stent grafts at a single institution between 2006 and 2013 were retrospectively reviewed. Graft patency and freedom from thrombolysis, major adverse limb event, and reintervention were determined by Kaplan-Meier analysis. The influence of relevant variables on clinical outcome was determined through univariate and multivariate Cox proportional hazards analyses.Viabahn stent grafts were placed in a total of 91 limbs in 61 patients (66% men; mean age, 69 ± 12 years) during the study period. Indication for intervention was either claudication (n = 59) or critical limb ischemia (n = 32), with the majority (70%) classified as TransAtlantic Inter-Society Consensus II C (n = 33) or D (n = 31) lesions. Mean follow-up was 38.3 months (range, 1-91 months). Postprocedural pharmacologic regimens included aspirin, clopidogrel, and warfarin (47%); indefinite aspirin and clopidogrel (46%); or aspirin and temporary clopidogrel (7%). Primary and secondary patency rates were 60%, 44%, and 36% and 95%, 82%, and 74% at 1 year, 3 years, and 5 years, respectively. Kaplan-Meier analysis demonstrated more aggressive antiplatelet/anticoagulation regimens to be associated with improved primary patency and freedom from reintervention. Cox proportional hazards analysis demonstrated TransAtlantic Inter-Society Consensus II D lesions, tobacco use, coronary artery disease, and smaller stent diameter to be independent risk factors for stent graft failure. Bleeding events were limited to those in the aspirin, clopidogrel, and warfarin group (11.6% [n = 5]; P = .052), although the majority of these events were not life-threatening, and only two cases required blood transfusion.Increasingly aggressive antithrombotic regimens after Viabahn stent graft placement trended toward improved overall clinical outcomes, although the marginal patency benefit observed with the addition of warfarin to dual antiplatelet therapy was tempered by an observed increased risk of bleeding complications. Longer term follow-up and multicenter studies are needed to further define optimal type and duration of antithrombotic therapy after endovascular peripheral interventions.

  View details for DOI 10.1016/j.jvs.2014.12.062

  View details for PubMedID 25704407

• Segmental Aortic Stiffening Contributes to Experimental Abdominal Aortic Aneurysm Development CIRCULATION Raaz, U., Zoellner, A. M., Schellinger, I. N., Toh, R., Nakagami, F., Brandt, M., Emrich, F. C., Kayama, Y., Eken, S., Adam, M., Maegdefessel, L., Hertel, T., Deng, A., Jagger, A., Buerke, M., Dalman, R. L., Spin, J. M., Kuhl, E., Tsao, P. S. 2015; 131 (20): 1783-1795

  Abstract

  Stiffening of the aortic wall is a phenomenon consistently observed in age and in abdominal aortic aneurysm (AAA). However, its role in AAA pathophysiology is largely undefined.Using an established murine elastase-induced AAA model, we demonstrate that segmental aortic stiffening precedes aneurysm growth. Finite-element analysis reveals that early stiffening of the aneurysm-prone aortic segment leads to axial (longitudinal) wall stress generated by cyclic (systolic) tethering of adjacent, more compliant wall segments. Interventional stiffening of AAA-adjacent aortic segments (via external application of surgical adhesive) significantly reduces aneurysm growth. These changes correlate with the reduced segmental stiffness of the AAA-prone aorta (attributable to equalized stiffness in adjacent segments), reduced axial wall stress, decreased production of reactive oxygen species, attenuated elastin breakdown, and decreased expression of inflammatory cytokines and macrophage infiltration, and attenuated apoptosis within the aortic wall, as well. Cyclic pressurization of segmentally stiffened aortic segments ex vivo increases the expression of genes related to inflammation and extracellular matrix remodeling. Finally, human ultrasound studies reveal that aging, a significant AAA risk factor, is accompanied by segmental infrarenal aortic stiffening.The present study introduces the novel concept of segmental aortic stiffening as an early pathomechanism generating aortic wall stress and triggering aneurysmal growth, thereby delineating potential underlying molecular mechanisms and therapeutic targets. In addition, monitoring segmental aortic stiffening may aid the identification of patients at risk for AAA.

  View details for DOI 10.1161/CIRCULATIONAHA.114.012377

  View details for Web of Science ID 000354610300015

  View details for PubMedID 25904646

  View details for PubMedCentralID PMC4439288

• Relationship of obstructive sleep apnea and cardiometabolic risk factors in elderly patients with abdominal aortic aneurysm SLEEP AND BREATHING Bianchi, V. E., Herbert, W. G., Myers, J., Ribisl, P. M., Miller, L. E., Dalman, R. L. 2015; 19 (2): 593-598

  Abstract

  This study seeks to determine the risks for obstructive sleep apnea (OSA) and cardiometabolic disease (CMR) in elderly patients with mild-moderate abdominal aortic aneurysms (AAA).Three hundred two elderly patients with diagnosed small AAA disease were subjects. CMR was assessed by several biomarkers, with special focus on the Lipid Accumulation Product (LAP) and the Triglyceride-Glucose Index (TyG Index), two validated screening indicators of CMR related to central obesity and insulin resistance, respectively. Analysis of OSA risk was assessed with the Berlin Questionnaire.The patients (60.6 %) had increased risk of OSA; those at high risk also were at increased (p < 0.05) risk for CMR (15/25 biomarkers).As a group, elderly AAA patients are at risk for both OSA and cardiometabolic disease. Given that OSA and CMR may both amplify risk for AAA expansion, these patients should be screened for OSA, and when indicated, referred for definitive evaluation and treatment.

  View details for DOI 10.1007/s11325-014-1053-2

  View details for Web of Science ID 000352909700023

  View details for PubMedID 25204854

• Geometry and respiratory-induced deformation of abdominal branch vessels and stents after complex endovascular aneurysm repair JOURNAL OF VASCULAR SURGERY Ullery, B. W., Suh, G., Lee, J. T., Liu, B., Stineman, R., Dalman, R. L., Cheng, C. P. 2015; 61 (4): 875-884

  Abstract

  This study quantified the geometry and respiration-induced deformation of abdominal branch vessels and stents after fenestrated (F-) and snorkel (Sn-) endovascular aneurysm repair (EVAR).Twenty patients (80% male; mean age, 75.2 ± 7.4 years; mean aneurysm diameter, 6.2 ± 1.8 cm) underwent computed tomography angiography during inspiratory and expiratory breath hold protocols after F-EVAR (n = 11) or Sn-EVAR (n = 9). Centerlines for the aorta and visceral vessels were extracted from three-dimensional models. Branch angles were computed relative to the orthogonal plane at the branch ostia, and end-stent angles of the left renal artery (LRA) and right renal artery (RRA) were computed relative to the distal stent orientation. The radius of peak curvature was defined by the circumscribed circle at the highest curvature.Sn-renal branches were more downward-angled than F-renal branches (P < .04). At the distal ends of the RRA stents, Sn-RRAs were angled greater than F-RRAs (P < .03) and had a smaller radius of peak curvature (P < .03). With expiration, the end-stent angle of Sn-LRAs increased by 4° ± 4° (P < .02) and exhibited a significant reduction of radius of curvature (P < .04). The unstented celiac arteries were more downward-angled (P < .02, inspiration), with a smaller radius of curvature (P < .00001), than the unstented superior mesenteric arteries. With expiration, the celiac arteries angled upwards by 9° ± 9° (P < .0005), which was greater than the superior mesenteric arteries (P < .03). At a median postoperative follow-up of 12.6 months (range, 1.0-37.1 months), branch vessel patency was 100%, serum creatinine levels remained stable, and one reintervention was required for a type III endoleak at the main body-LRA stent interface.Sn-renals were angled more inferiorly at the branch and more angulated at the stent end than F-renals due to stent placement strategies. Sn-LRAs exhibited a significant change in end-stent angle and curvature during respiration, a finding that may compromise long-term durability for parallel stent graft configurations. Further investigation is warranted to better optimize anatomic, patient, and branch vessel stent selection between fenestrated and snorkel strategies and their relationship to long-term patency.

  View details for DOI 10.1016/j.jvs.2014.11.075

  View details for Web of Science ID 000351776100005

  View details for PubMedID 25601499

• Reproducibility of the Veterans Physical Activity Questionnaire in an Elderly Population JOURNAL OF PHYSICAL ACTIVITY & HEALTH Betz, H. H., Myers, J., Jaffe, A., Smith, K., Dalman, R. 2015; 12 (3): 376-381

  Abstract

  Quantifying lifetime physical activity using self-reported measures is challenging due to reliance on recall, especially in older populations. The purpose of this study was to determine the 1-year reproducibility of the Veterans Physical Activity Questionnaire (VAPAQ) in a cohort of patients with documented abdominal aortic aneurysm disease (AAA).Subjects included men (n = 52) and women (n = 3) enrolled in AAA STOP, a randomized trial designed to test the ability of supervised exercise training to modify AAA biology and early disease progression.The overall correlation coefficient for lifetime recreational energy expenditure between the 2 examinations was 0.93 (P < .001), with an overall difference of 26 kcal/week, a typical error (standard deviation of the differences) of 171 kcals/week, and a coefficient of variation (CV) of 15.5%.The VAPAQ is a reproducible tool to quantify lifetime energy expenditure in older adults with documented vascular disease.

  View details for DOI 10.1123/jpah.2013-0124

  View details for Web of Science ID 000354755300013

  View details for PubMedID 24763187

• TElmisartan in the management of abDominal aortic aneurYsm (TEDY): The study protocol for a randomized controlled trial. Trials Morris, D. R., Cunningham, M. A., Ahimastos, A. A., Kingwell, B. A., Pappas, E., Bourke, M., Reid, C. M., Stijnen, T., Dalman, R. L., Aalami, O. O., Lindeman, J. H., Norman, P. E., Walker, P. J., Fitridge, R., Bourke, B., Dear, A. E., Pinchbeck, J., Jaeggi, R., Golledge, J. 2015; 16: 274-?

  Abstract

  Experimental studies suggest that angiotensin II plays a central role in the pathogenesis of abdominal aortic aneurysm. This trial aims to evaluate the efficacy of the angiotensin receptor blocker telmisartan in limiting the progression of abdominal aortic aneurysm.Telmisartan in the management of abdominal aortic aneurysm (TEDY) is a multicentre, parallel-design, randomised, double-blind, placebo-controlled trial with an intention-to-treat analysis. We aim to randomly assign 300 participants with small abdominal aortic aneurysm to either 40 mg of telmisartan or identical placebo and follow patients over 2 years. The primary endpoint will be abdominal aortic aneurysm growth as measured by 1) maximum infra-renal aortic volume on computed tomographic angiography, 2) maximum orthogonal diameter on computed tomographic angiography, and 3) maximum diameter on ultrasound. Secondary endpoints include change in resting brachial blood pressure, abdominal aortic aneurysm biomarker profile and health-related quality of life. TEDY is an international collaboration conducted from major vascular centres in Australia, the United States and the Netherlands.Currently, no medication has been convincingly demonstrated to limit abdominal aortic aneurysm progression. TEDY will examine the potential of a promising treatment strategy for patients with small abdominal aortic aneurysms.Australian and Leiden study centres: Australian New Zealand Clinical Trials Registry ACTRN12611000931976 , registered on 30 August 2011; Stanford study centre: clinicaltrials.gov NCT01683084 , registered on 5 September 2012.

  View details for DOI 10.1186/s13063-015-0793-z

  View details for PubMedID 26081587

• CCR2 inhibition sequesters multiple subsets of leukocytes in the bone marrow. Scientific reports Fujimura, N., Xu, B., Dalman, J., Deng, H., Aoyama, K., Dalman, R. L. 2015; 5: 11664-?

  Abstract

  Chemokine receptor CCR2 mediates monocyte mobilization from the bone marrow (BM) and subsequent migration into target tissues. The degree to which CCR2 is differentially expressed in leukocyte subsets, and the contribution of CCR2 to these leukocyte mobilization from the BM are poorly understood. Using red fluorescence protein CCR2 reporter mice, we found heterogeneity in CCR2 expression among leukocyte subsets in varying tissues. CCR2 was highly expressed by inflammatory monocytes, dendritic cells, plasmacytoid dendritic cells and NK cells in all tissues. Unexpectedly, more than 60% of neutrophils expressed CCR2, albeit at low levels. CCR2 expression in T cells, B cells and NK T cells was greatest in the BM compared to other tissues. Genetic CCR2 deficiency markedly sequestered all leukocyte subsets in the BM, with reciprocal reduction noted in the peripheral blood and spleen. CCR2 inhibition via treatment with CCR2 signaling inhibitor propagermanium produced similar effects. Propagermanium also mitigated lipopolysaccharide-induced BM leukocyte egress. Consistent with its functional significance, CCR2 antibody staining revealed surface CCR2 expression within a subset of BM neutrophils. These results demonstrate the central role CCR2 plays in mediating leukocyte mobilization from the BM, and suggest a role for CCR2 inhibition in managing monocytes/macrophages-mediated chronic inflammatory conditions.

  View details for DOI 10.1038/srep11664

  View details for PubMedID 26206182

• A longitudinal comparison of hemodynamics and intraluminal thrombus deposition in abdominal aortic aneurysms. American journal of physiology. Heart and circulatory physiology Arzani, A., Suh, G., Dalman, R. L., Shadden, S. C. 2014; 307 (12): H1786-95

  Abstract

  Abdominal aortic aneurysm (AAA) is often accompanied by in traluminal thrombus (ILT), which complicates AAA progression and risk of rupture. Patient-specific computational fluid dynamics modeling of 10 small human AAA was performed to investigate relations between hemodynamics and ILT progression. The patients were imaged using magnetic resonance twice in a 2- to 3-yr interval. Wall content data were obtained by a planar T1-weighted fast spin echo black-blood scan, which enabled quantification of thrombus thickness at midaneurysm location during baseline and followup. Computational simulations with patient-specific geometry and boundary conditions were performed to quantify the hemodynamic parameters of time-averaged wall shear stress (TAWSS), oscillatory shear index (OSI), and mean exposure time at baseline. Spatially resolved quantifications of the change in ILT thickness were compared with the different hemodynamic parameters. Regions of low OSI had the strongest correlation with ILT growth and demonstrated a statistically significant correlation coefficient. Prominent regions of high OSI (>0.4) and low TAWSS (<1 dyn/cm(2)) did not appear to coincide with locations of thrombus deposition.

  View details for DOI 10.1152/ajpheart.00461.2014

  View details for PubMedID 25326533

  View details for PubMedCentralID PMC4269702

• A longitudinal comparison of hemodynamics and intraluminal thrombus deposition in abdominal aortic aneurysms AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY Arzani, A., Suh, G., Dalman, R. L., Shadden, S. C. 2014; 307 (12): H1786-H1795

  View details for DOI 10.1152/ajpheart.00461.2014

  View details for Web of Science ID 000346478200011

  View details for PubMedID 25326533

• ACE Inhibitors Potently Reduce Vascular Inflammation, Results of an Open Proof-Of-Concept Study in the Abdominal Aortic Aneurysm PLOS ONE Kortekaas, K. E., Meijer, C. A., Hinnen, J. W., Dalman, R. L., Xu, B., Hamming, J. F., Lindeman, J. H. 2014; 9 (12)

  Abstract

  Independent of their blood pressure lowering effect, ACE inhibitors are thought to reduce vascular inflammation. The clinical relevance of this effect is unclear with the current knowledge. Abdominal aortic aneurysms (AAA) are characterized by a broad, non-specific inflammatory response, and thus provide a clinical platform to evaluate the anti-inflammatory potential of ACE inhibitors.Eleven patients scheduled for open AAA repair received ramipril (5 mg/day) during 2-4 weeks preceding surgery. Aortic wall samples were collected during surgery, and compared to matched samples obtained from a biobank. An anti-inflammatory potential was evaluated in a comprehensive analysis that included immunohistochemistry, mRNA and protein analysis. A putative effect of ACE inhibitors on AAA growth was tested separately by comparing 18-month growth rate of patients on ACE inhibitors (n = 82) and those not taking ACE inhibitors (n = 204). Ramipril reduces mRNA expression of multiple pro-inflammatory cytokines such as IL-1β, IL-6, IL-8, TNF -α, Interferon-[Formula: see text], and MCP-1, as well as aortic wall IL-8 and MCP-1 (P = 0.017 and 0.008, respectively) protein content. The is followed by clear effects on cell activation that included a shift towards anti-inflammatory macrophage (M2) subtype. Evaluation of data from the PHAST cohort did not indicate an effect of ACE inhibitors on 18-month aneurysm progression (mean difference at 18 months: -0.24 mm (95% CI: -0.90-0.45, P = NS).ACE inhibition quenches multiple aspects of vascular inflammation in AAA. However, this does not translate into reduced aneurysm growth.Nederlands Trial Register 1345.

  View details for DOI 10.1371/journal.pone.0111952

  View details for Web of Science ID 000346382500065

  View details for PubMedID 25474105

• miR-24 limits aortic vascular inflammation and murine abdominal aneurysm development NATURE COMMUNICATIONS Maegdefessel, L., Spin, J. M., Raaz, U., Eken, S. M., Toh, R., Azuma, J., Adam, M., Nagakami, F., Heymann, H. M., Chernugobova, E., Jin, H., Roy, J., Hultgren, R., Caidahl, K., Schrepfer, S., Hamsten, A., Eriksson, P., McConnell, M. V., Dalman, R. L., Tsao, P. S. 2014; 5

  Abstract

  Identification and treatment of abdominal aortic aneurysm (AAA) remain among the most prominent challenges in vascular medicine. MicroRNAs (miRNAs) are crucial regulators of cardiovascular pathology and represent intriguing targets to limit AAA expansion. Here we show, by using two established murine models of AAA disease along with human aortic tissue and plasma analysis, that miR-24 is a key regulator of vascular inflammation and AAA pathology. In vivo and in vitro studies reveal chitinase 3-like 1 (Chi3l1) to be a major target and effector under the control of miR-24, regulating cytokine synthesis in macrophages as well as their survival, promoting aortic smooth muscle cell migration and cytokine production, and stimulating adhesion molecule expression in vascular endothelial cells. We further show that modulation of miR-24 alters AAA progression in animal models, and that miR-24 and CHI3L1 represent novel plasma biomarkers of AAA disease progression in humans.

  View details for DOI 10.1038/ncomms6214

  View details for Web of Science ID 000343982800003

  View details for PubMedCentralID PMC4217126

• Comparison of fenestrated endografts and the snorkel/chimney technique 28th Annual Meeting of the Western-Vascular-Society Lee, J. T., Lee, G. K., Chandra, V., Dalman, R. L. MOSBY-ELSEVIER. 2014: 849–56

  Abstract

  Recent approval by the Food and Drug Administration of custom fenestrated endografts has increased endovascular options for patients with short-neck or juxtarenal abdominal aortic aneurysms (AAAs). We sought to compare the early learning curve at a single institution of fenestrated repair vs the snorkel technique.From 2009 to 2013, we performed 57 consecutive snorkel procedures for juxtarenal AAAs in an Institutional Review Board-approved prospective cohort, and since the summer of 2012, we gained access to the Food and Drug Administration-approved custom fenestrated device. Patient demographics, imaging, and operative techniques were compared between the first 15 cases for each of the snorkel (sn-EVAR) and fenestrated (f-EVAR) endovascular aneurysm repair (EVAR) techniques.Patient demographics and AAA morphology on preoperative imaging were similar between the groups. Operative time tended to be similar in the 3- to 4-hour range, with more fluoroscopy time and less contrast material used in f-EVAR than in sn-EVAR (P < .05) because of differing strategies of renal premarking. Larger delivery systems for f-EVAR required a higher rate of iliac conduits (40% vs 0%). Perioperative complications, short-term renal patency rates, and evidence of acute kidney injury were similar.The early experience of f-EVAR was similar to that of sn-EVAR in terms of patient demographics, case selection, and procedural characteristics. A significant portion of the learning curve for both procedures, particularly for f-EVAR, lies in the preoperative planning of fenestrations and the cannulation of branch vessels. Similar short-term postoperative outcomes between these two particular techniques indicate that both will have utility in the treatment of high-risk patients with complex anatomy.

  View details for DOI 10.1016/j.jvs.2014.03.255

  View details for Web of Science ID 000343316600003

• Renal function changes after snorkel/chimney repair of juxtarenal aneurysms. Journal of vascular surgery Lee, J. T., Varu, V. N., Tran, K., Dalman, R. L. 2014; 60 (3): 563-570

  Abstract

  The snorkel approach for endovascular aneurysm repair (EVAR) has been found to be a safe and viable alternative to open repair for juxtarenal abdominal aortic aneurysms with good short-term outcomes. Concerns about long-term durability and renal branch patency with this technique have been raised with the increasing availability of fenestrated devices. We sought to evaluate renal function changes in patients undergoing "snorkel" EVAR (sn-EVAR).Patients who underwent sn-EVAR from 2009 to 2012 were included in this analysis. Creatinine values were obtained throughout the patient's preoperative, perioperative, and postoperative course. Glomerular filtration rate (GFR) was estimated by the simplified Modification of Diet in Renal Disease formula. Acute renal dysfunction was analyzed according to the RIFLE (Risk, Injury, Failure, Loss, End stage) criteria, whereas chronic renal dysfunction was stratified by the chronic kidney disease staging system.Forty-three consecutive patients underwent sn-EVAR (31 double renal, 12 single renal) for juxtarenal aortic aneurysms. Mean follow-up time was 21 months. Mean aneurysm size was 6.6 cm (range, 5.1-10.5 cm) with anatomy not suitable for treatment with standard EVAR (mean neck length, 1.6 mm); 74 renal snorkel stents were placed in these patients with a 2-year primary patency of 95%. On average, the cohort at baseline was stratified as having moderate renal dysfunction. Mean baseline, maximum postoperative, and latest follow-up creatinine concentrations were 1.20, 1.49, and 1.43, respectively (P = .004). Mean baseline, maximum postoperative, and latest follow-up GFRs were 57.4, 47.8, and 49.2, respectively (P = .014). With use of RIFLE criteria, 14 patients (32.6%) experienced some form of acute kidney injury, although 10 of these patients (23.3%) were classified as mild (25%-50% decline in GFR). On analysis without the RIFLE criteria, 21.4% of patients had postoperative creatinine concentration >1.5 mg/dL, 28.6% had postoperative creatinine concentration increase >30%, and 28.6% had postoperative GFR decline >30%. For the entire study cohort at latest follow-up, 51% experienced no decline of chronic renal dysfunction and 8.1% had improvement in renal function. Renal function declined by one stage in 35.2% of the cohort and by two stages in 5.4%. On analysis without chronic kidney disease staging, 24.3% of patients had latest follow-up creatinine concentration >1.5 mg/dL, 29.7% had latest follow-up creatinine concentration increase >30%, and 24.3% had latest follow-up GFR decline >30%. Mean survival time from significant renal decline was 23.4 months.sn-EVAR continues to demonstrate a high rate of technical success and results in only mild rates of acute and midterm renal function decline according to a number of established definitions for renal dysfunction. Continued monitoring of renal function, renal stent behavior, and abdominal aortic aneurysm sac changes remains critically important in the long-term management of patients undergoing sn-EVAR, particularly given the high comorbidities associated with juxtarenal aortic aneurysms.

  View details for DOI 10.1016/j.jvs.2014.03.239

  View details for PubMedID 24785683

• Rapamycin limits the growth of established experimental abdominal aortic aneurysms. European journal of vascular and endovascular surgery Rouer, M., Xu, B. H., Xuan, H. J., Tanaka, H., Fujimura, N., Glover, K. J., Furusho, Y., Gerritsen, M., Dalman, R. L. 2014; 47 (5): 493-500

  Abstract

  Abdominal aortic aneurysm (AAA) is a chronic inflammatory disease affecting 4-8% of men older than 60 years. No pharmacologic strategies limit disease progression, aneurysm rupture, or aneurysm-related death. We examined the ability of rapamycin to limit the progression of established experimental AAAs.AAAs were created in 10-12-week-old male C57BL/6J mice via the porcine pancreatic elastase (PPE) infusion method. Beginning 4 days after PPE infusion, mice were treated with rapamycin (5 mg/kg/day) or an equal volume of vehicle for 10 days. AAA progression was monitored by serial ultrasound examination. Aortae were harvested for histological analyses at sacrifice.Three days after PPE infusion, prior to vehicle or rapamycin treatment, aneurysms were enlarging at an equal rate between groups. In the rapamycin group, treatment reduced aortic enlargement by 38%, and 53% at 3 and 10 days, respectively. On histological analysis, medial elastin and smooth muscle cell populations were relatively preserved in the rapamycin group. Rapamycin treatment also reduced mural macrophage density and neoangiogenesis.Rapamycin limits the progression of established experimental aneurysms, increasing the translational potential of mechanistic target of rapamycin-related AAA inhibition strategies.

  View details for DOI 10.1016/j.ejvs.2014.02.006

  View details for PubMedID 24629569

• Gaps in preoperative surveillance and rupture of abdominal aortic aneurysms among Medicare beneficiaries. Journal of vascular surgery Mell, M. W., Baker, L. C., Dalman, R. L., Hlatky, M. A. 2014; 59 (3): 583-588

  Abstract

  Screening and surveillance are recommended in the management of small abdominal aortic aneurysms (AAAs). Gaps in surveillance after early diagnosis may lead to unrecognized AAA growth, rupture, and death. This study investigates the frequency and predictors of rupture of previously diagnosed AAAs.Data were extracted from Medicare claims for patients who underwent AAA repair between 2006 and 2009. Relevant preoperative abdominal imaging exams were tabulated up to 5 years prior to AAA repair. Repair for ruptured AAAs was compared with repair for intact AAAs for those with an early diagnosis of an AAA, defined as having received imaging at least 6 months prior to surgery. Gaps in surveillance were defined as no image within 1 year of surgery or no imaging for more than a 2-year time span after the initial image. Logistic regression was used to examine independent predictors of rupture despite early diagnosis.A total of 9298 patients had repair after early diagnosis, with rupture occurring in 441 (4.7%). Those with ruptured AAAs were older (80.2 ± 6.9 vs 77.6 ± 6.2 years; P < .001), received fewer images prior to repair (5.7 ± 4.1 vs 6.5 ± 3.5; P = .001), were less likely to be treated in a high-volume hospital (45.4% vs 59.5%; P < .001), and were more likely to have had gaps in surveillance (47.4% vs 11.8%; P < .001) compared with those receiving repair for intact AAAs. After adjusting for medical comorbidities, gaps in surveillance remained the largest predictor of rupture in a multivariate analysis (odds ratio, 5.82; 95% confidence interval, 4.64-7.31; P < .001).Despite previous diagnosis of AAA, many patients experience rupture prior to repair. Improved mechanisms for surveillance are needed to prevent rupture and ensure timely repair for patients with AAAs.

  View details for DOI 10.1016/j.jvs.2013.09.032

  View details for PubMedID 24246537

• Effect of exercise on patient specific abdominal aortic aneurysm flow topology and mixing. International journal for numerical methods in biomedical engineering Arzani, A., Les, A. S., Dalman, R. L., Shadden, S. C. 2014; 30 (2): 280-295

  Abstract

  Computational fluid dynamics modeling was used to investigate changes in blood transport topology between rest and exercise conditions in five patient-specific abdominal aortic aneurysm models. MRI was used to provide the vascular anatomy and necessary boundary conditions for simulating blood velocity and pressure fields inside each model. Finite-time Lyapunov exponent fields and associated Lagrangian coherent structures were computed from blood velocity data and were used to compare features of the transport topology between rest and exercise both mechanistically and qualitatively. A mix-norm and mix-variance measure based on fresh blood distribution throughout the aneurysm over time were implemented to quantitatively compare mixing between rest and exercise. Exercise conditions resulted in higher and more uniform mixing and reduced the overall residence time in all aneurysms. Separated regions of recirculating flow were commonly observed in rest, and these regions were either reduced or removed by attached and unidirectional flow during exercise, or replaced with regional chaotic and transiently turbulent mixing, or persisted and even extended during exercise. The main factor that dictated the change in flow topology from rest to exercise was the behavior of the jet of blood penetrating into the aneurysm during systole. Copyright © 2013 John Wiley & Sons, Ltd.

  View details for DOI 10.1002/cnm.2601

  View details for PubMedID 24493404

• Pathogenesis of Abdominal Aortic Aneurysms: MicroRNAs, Proteases, Genetic Associations. Annual review of medicine Maegdefessel, L., Dalman, R. L., Tsao, P. S. 2014; 65: 49-62

  Abstract

  Abdominal aortic aneurysm (AAA) disease is a common, morbid, and highly lethal pathology. Extraordinary efforts have been launched to determine the molecular and pathophysiological characteristics of AAAs. Although surgery is highly effective in preventing death by rupture for larger AAAs, no guidance or preventive therapy is currently available for the >90% of patients whose aneurysms are below the surgical threshold. Predictive animal models of AAA as well as human pathological samples have revealed a complex circuit of AAA formation and progression. The proteolytic destruction of matrix components of the aorta by different proteases has been extensively studied over many years. Recently, a novel class of small noncoding RNAs, called microRNAs, was identified as "fine-tuners" of the translational output of target genes; they act by promoting mRNA degradation. Their therapeutic potential in limiting AAA development appears very intriguing. Further, current studies assessing genetic and heritable associations for AAA disease have provided great insight into its pathogenesis, potentially enabling us to better clinically manage affected patients.

  View details for DOI 10.1146/annurev-med-101712-174206

  View details for PubMedID 24274177

• A randomized trial of exercise training in abdominal aortic aneurysm disease. Medicine and science in sports and exercise Myers, J., McElrath, M., Jaffe, A., Smith, K., Fonda, H., Vu, A., Hill, B., Dalman, R. 2014; 46 (1): 2-9

  Abstract

  Screening programs and greater public awareness have increased the recognition of early abdominal aortic aneurysm (AAA) disease. No medical therapy has proven effective in limiting AAA progression, and little is known regarding the safety and efficacy of exercise training in these patients. We evaluated the safety and efficacy of up to 3 years of training in patients with early (≤5.5 cm) AAA disease.One hundred forty patients with small AAAs (72±8 years) were randomized to exercise training (n=72) or usual care (n=68). Exercise subjects participated in a combination of in-house and home training for up to 3 years. Cardiopulmonary exercise testing (CPX) was performed at baseline and 3, 12, 24, and 36 months. Comparisons were made for AAA expansion, safety, CPX responses, and weekly energy expenditure.Average duration of participation was 23.4 ±9.6 months; 81% of subjects completed ≥ 1 year. No adverse clinical events or excessive AAA growth rates related to training occurred. Exercise subjects expended a mean 1999±1030 kcals/week. Increases in peak exercise time and estimated METs occurred at the 3 month and 1, 2, and 3-year evaluations (p<0.01 between groups). A significant between-group interaction occurred for VO2 at the ventilatory threshold (p=0.02), and submaximal heart rate was significantly reduced among exercise subjects. Neither exercise status nor level of fitness significantly influenced rate of AAA enlargement.These results support the safety and efficacy of training in patients with small AAA, a population for which few previous data are available. Despite advanced age and co-morbidities, training up to 3 years was well tolerated and sustainable in AAA patients. Training did not influence rate of AAA enlargement.

  View details for DOI 10.1249/MSS.0b013e3182a088b8

  View details for PubMedID 23793234

• miR-24 limits aortic vascular inflammation and murine abdominal aneurysm development. Nature communications Maegdefessel, L., Spin, J. M., Raaz, U., Eken, S. M., Toh, R., Azuma, J., Adam, M., Nakagami, F., Heymann, H. M., Chernogubova, E., Jin, H., Roy, J., Hultgren, R., Caidahl, K., Schrepfer, S., Hamsten, A., Eriksson, P., McConnell, M. V., Dalman, R. L., Tsao, P. S. 2014; 5: 5214-?

  Abstract

  Identification and treatment of abdominal aortic aneurysm (AAA) remain among the most prominent challenges in vascular medicine. MicroRNAs (miRNAs) are crucial regulators of cardiovascular pathology and represent intriguing targets to limit AAA expansion. Here we show, by using two established murine models of AAA disease along with human aortic tissue and plasma analysis, that miR-24 is a key regulator of vascular inflammation and AAA pathology. In vivo and in vitro studies reveal chitinase 3-like 1 (Chi3l1) to be a major target and effector under the control of miR-24, regulating cytokine synthesis in macrophages as well as their survival, promoting aortic smooth muscle cell migration and cytokine production, and stimulating adhesion molecule expression in vascular endothelial cells. We further show that modulation of miR-24 alters AAA progression in animal models, and that miR-24 and CHI3L1 represent novel plasma biomarkers of AAA disease progression in humans.

  View details for DOI 10.1038/ncomms6214

  View details for PubMedID 25358394

  View details for PubMedCentralID PMC4217126

• Agreement Between Activity-Monitoring Devices During Home Rehabilitation: A Substudy of the AAA STOP Trial JOURNAL OF AGING AND PHYSICAL ACTIVITY Myers, J., Dupain, M., Vu, A., Jaffe, A., Smith, K., Fonda, H., Dalman, R. 2014; 22 (1): 87-95

  Abstract

  As part of a home-based rehabilitation program, 24 older adult patients (71 ± 3 years) with abdominal aortic aneurysm (AAA) disease underwent 3 days (12 awake hr/day) of activity monitoring using an accelerometer (ACC), a pedometer, and a heart rate (HR) monitor, and recorded hourly activity logs. Subjects then underwent an interview to complete a 3-day activity recall questionnaire (3-DR). Mean energy expenditure (EE) in kcals/ day for HR, ACC, and 3-DR were 1,687 ± 458, 2,068 ± 529, and 1,974 ± 491, respectively. Differences in EE were not significant between 3-DR and ACC, but HR differed from both ACC (p < .001) and 3-DR (p < .01). ACC and 3-DR had the highest agreement, with a coefficient of variation of 7.9% and r = .86. Thus, ACC provided a reasonably accurate reflection of EE based the criterion measure, an activity recall questionnaire. ACC can be effectively used to monitor EE to achieve an appropriate training stimulus during home-based cardiac rehabilitation.

  View details for DOI 10.1123/JAPA:2012-0133

  View details for Web of Science ID 000329896100009

  View details for PubMedID 23416349

• Respiratory-Induced 3D Deformations of the Renal Arteries Quantified With Geometric Modeling During Inspiration and Expiration Breath-Holds of Magnetic Resonance Angiography JOURNAL OF MAGNETIC RESONANCE IMAGING Suh, G., Choi, G., Draney, M. T., Herfkens, R. J., Dalman, R. L., Cheng, C. P. 2013; 38 (6): 1325-1332

  Abstract

  PURPOSE: To quantify renal artery deformation due to respiration using magnetic resonance (MR) image-based geometric analysis. MATERIALS AND METHODS: Five males were imaged with contrast-enhanced MR angiography during inspiratory and expiratory breath-holds. From 3D models of the abdominal aorta, left and right renal arteries (LRA and RRA), we quantified branching angle, curvature, peak curve angle, axial length, and locations of branch points. RESULTS: With expiration, maximum curvature changes were 0.054 ± 0.025 mm(-1) (P < 0.01), and curve angle at the most proximal curvature peak increased by 8.0 ± 4.5° (P < 0.05) in the LRA. Changes in maximum curvature and curve angles were not significant in the RRA. The first renal bifurcation point translated superiorly and posteriorly by 9.7 ± 3.6 mm (P < 0.005) and 3.5 ± 2.1 mm (P < 0.05), respectively, in the LRA, and 10.8 ± 6.1 mm (P < 0.05) and 3.6 ± 2.5 mm (P < 0.05), respectively, in the RRA. Changes in branching angle, axial length, and renal ostia locations were not significant. CONCLUSION: The LRA and RRA deformed and translated significantly. Greater deformation of the LRA as compared to the RRA may be due to asymmetric anatomy and mechanical support by the inferior vena cava. The presented methodology can extend to quantification of deformation of diseased and stented arteries to help renal artery implant development. J. Magn. Reson. Imaging 2013;. © 2013 Wiley Periodicals, Inc.

  View details for DOI 10.1002/jmri.24101

  View details for Web of Science ID 000327756800003

  View details for PubMedID 23553967

• Integrin-Targeted Molecular Imaging of Experimental Abdominal Aortic Aneurysms by 18F-labeled Arg-Gly-Asp Positron-Emission Tomography. Circulation. Cardiovascular imaging Kitagawa, T., Kosuge, H., Chang, E., James, M. L., Yamamoto, T., Shen, B., Chin, F. T., Gambhir, S. S., Dalman, R. L., McConnell, M. V. 2013; 6 (6): 950-956

  Abstract

  Background- Both inflammation and neoangiogenesis contribute to abdominal aortic aneurysm (AAA) disease. Arg-Gly-Asp-based molecular imaging has been shown to detect the integrin αvβ3. We studied a clinical dimeric (18)F-labeled Arg-Gly-Asp positron-emission tomography (PET) agent ((18)F-FPPRGD2) for molecular imaging of experimental AAAs. Methods and Results- Murine AAAs were induced in Apo-E-deficient mice by angiotensin II infusion, with monitoring of aortic diameter on ultrasound. AAA (n=10) and saline-infused control mice (n=7) were injected intravenously with (18)F-FPPRGD2, as well as an intravascular computed tomography contrast agent, then scanned using a small-animal PET/computed tomography scanner. Aortic uptake of (18)F-FPPRGD2 was quantified by percentage-injected dose per gram and target-to-=0.003; median target-to-=0.0008). Ex vivo autoradiography demonstrated high uptake of (18)F-FPPRGD2 into the AAA wall, with immunohistochemistry showing substantial cluster of differentiation (CD)-11b(+) macrophages and CD-31(+) neovessels. Target-to-=-0.29, P=0.41) but did strongly correlate with both mural macrophage density (r=0.79, P=0.007) and neovessel counts (r=0.87, P=0.001) on immunohistochemistry. Conclusions- PET imaging of experimental AAAs using (18)F-FPPRGD2 detects biologically active disease, correlating to the degree of vascular inflammation and neoangiogenesis. This may provide a clinically translatable molecular imaging approach to characterize AAA biology to predict risk beyond size alone.

  View details for DOI 10.1161/CIRCIMAGING.113.000234

  View details for PubMedID 23995363

• Factors impacting follow-up care after placement of temporary inferior vena cava filters 27th Annual Meeting of the Western-Vascular-Society Gyang, E., Zayed, M., Harris, E. J., Lee, J. T., Dalman, R. L., Mell, M. W. MOSBY-ELSEVIER. 2013: 440–45

  Abstract

  Rates of inferior vena cava (IVC) filter retrieval have remained suboptimal, in part because of poor follow-up. The goal of our study was to determine demographic and clinical factors predictive of IVC filter follow-up care in a university hospital setting.We reviewed 250 consecutive patients who received an IVC filter placement with the intention of subsequent retrieval between March 2009 and October 2010. Patient demographics, clinical factors, and physician specialty were evaluated. Multivariate logistic regression analysis was performed to identify variables predicting follow-up care.In our cohort, 60.7% of patients received follow-up care; of those, 93% had IVC filter retrieval. Major indications for IVC filter placement were prophylaxis for high risk surgery (53%) and venous thromboembolic event with contraindication and/or failure of anticoagulation (39%). Follow-up care was less likely for patients discharged to acute rehabilitation or skilled nursing facilities (P < .0001), those with central nervous system pathology (eg, cerebral hemorrhage or spinal fracture; P < .0001), and for those who did not receive an IVC filter placement by a vascular surgeon (P < .0001). In a multivariate analysis, discharge home (odds ratio [OR], 4.0; 95% confidence interval [CI], 1.99-8.2; P < .0001), central nervous system pathology (OR, 0.46; 95% CI, 0.22-0.95; P = .04), and IVC filter placement by the vascular surgery service (OR, 4.7; 95% CI, 2.3-9.6; P < .0001) remained independent predictors of follow-up care. Trauma status and distance of residence did not significantly impact likelihood of patient follow-up.Service-dependent practice paradigms play a critical role in patient follow-up and IVC filter retrieval rates. Nevertheless, specific patient populations are more prone to having poorer rates of follow-up. Such trends should be factored into institutional quality control goals and patient-centered care.

  View details for DOI 10.1016/j.jvs.2012.12.085

  View details for Web of Science ID 000322759500029

  View details for PubMedID 23588109

• EVAR Deployment in Anatomically Challenging Necks Outside the IFU 63rd Vascular Annual Meeting of the Society-for-Vascular-Surgery (SVS) Lee, J. T., Ullery, B. W., Zarins, C. K., Olcott, C., Harris, E. J., Dalman, R. L. W B SAUNDERS CO LTD. 2013: 65–73

  Abstract

  Treatment of abdominal aortic aneurysms with high-risk anatomy (neck length <10-15 mm, neck angle >60°) using commercially available devices has become increasingly common with expanding institutional experience. We examined whether placement of approved devices in short angled necks provides acceptable durability at early and intermediate time points.A total of 218 patients (197 men, 21 women) at a single academic center underwent endovascular aneurysm repair (EVAR) with a commercially available device between January 2004 and December 2007. Available medical records, pre- and postoperative imaging, and clinical follow-up were retrospectively reviewed. Patients were divided into those with suitable anatomy (instructions for use, IFU) for EVAR and those with high-risk anatomic aneurysm characteristics (non-IFU).IFU (n = 143) patients underwent repair with Excluder (40%), AneuRx (34%), and Zenith (26%) devices, whereas non-IFU (n = 75) were preferentially treated with Zenith (57%) over Excluder (25%) and AneuRx (17%). Demographics and medical comorbidities between the groups were similar. Operative mortality was 1.4% (2.1% IFU, 0% non-IFU) with mean follow-up of 35 months (range 12-72). Non-IFU patients tended to have larger sac diameters (46.7% ≥60 mm) with shorter (30.7% ≤10 mm), conical (49.3%), and more angled (68% >60°) necks (all p < .05 compared with IFU patients). Operative characteristics revealed that the non-IFU patients were more likely to be treated utilizing suprarenal fixation devices, to require placement of proximal cuffs (13.3% vs. 2.1%, p = .003), and needed increased fluoroscopy time (31 vs. 25 minutes, p = .02). Contrast dose was similar between groups (IFU = 118 mL, non-IFU = 119 mL, p = .95). There were no early or late surgical conversions. Rates of migration, endoleak, need for reintervention, sac regression, and freedom from aneurysm-related death were similar between the groups (p > .05).EVAR may be performed safely in high-risk patients with unfavorable neck anatomy using particular commercially available endografts. In our experience, the preferential use of active suprarenal fixation and aggressive use of proximal cuffs is associated with optimal results in these settings. Mid-term outcomes are comparable with those achieved in patients with suitable anatomy using a similar range of EVAR devices. Careful and mandatory long-term follow-up will be necessary to confirm the benefit of treating these high-risk anatomic patients.

  View details for DOI 10.1016/j.ejvs.2013.03.027

  View details for Web of Science ID 000321883200013

  View details for PubMedID 23628325

• Respiration-induced Deformations of the Superior Mesenteric and Renal Arteries in Patients with Abdominal Aortic Aneurysms. Journal of vascular and interventional radiology Suh, G., Choi, G., Herfkens, R. J., Dalman, R. L., Cheng, C. P. 2013; 24 (7): 1035-1042

  Abstract

  To quantify respiration-induced deformations of the superior mesenteric artery (SMA), left renal artery (LRA), and right renal artery (RRA) in patients with small abdominal aortic aneurysms (AAAs).Sixteen men with AAAs (age 73 y ± 7) were imaged with contrast-enhanced magnetic resonance angiography during inspiratory and expiratory breath-holds. Centerline paths of the aorta and visceral arteries were acquired by geometric modeling and segmentation techniques. Vessel translations and changes in branching angle and curvature resulting from respiration were computed from centerline paths.With expiration, the SMA, LRA, and RRA bifurcation points translated superiorly by 12.4mm ± 9.5, 14.5mm ± 8.8, and 12.7mm ± 6.4 (P < .001), and posteriorly by 2.2mm ± 2.7, 4.9mm ± 4.2, and 5.6mm ± 3.9 (P < .05), respectively, and the SMA translated rightward by 3.9mm ± 4.9 (P < .01). With expiration, the SMA, LRA, and RRA angled upward by 9.7° ± 6.4, 7.5° ± 7.8, and 4.9° ± 5.3, respectively (P < .005). With expiration, mean curvature increased by 0.02mm(-1) ± 0.01, 0.01mm(-1) ± 0.01, and 0.01mm(-1) ± 0.01 in the SMA, LRA, and RRA, respectively (P < .05). For inspiration and expiration, RRA curvature was greater than in other vessels (P < .025).With expiration, the SMA, LRA, and RRA translated superiorly and posteriorly as a result of diaphragmatic motion, inducing upward angling of vessel branches and increased curvature. In addition, the SMA exhibited rightward translation with expiration. The RRA was significantly more tortuous, but deformed less than the other vessels during respiration.

  View details for DOI 10.1016/j.jvir.2013.04.006

  View details for PubMedID 23796090

  View details for PubMedCentralID PMC3694359

• Late diagnosis of abdominal aortic aneurysms substantiates underutilization of abdominal aortic aneurysm screening for Medicare beneficiaries. Journal of vascular surgery Mell, M. W., Hlatky, M. A., Shreibati, J. B., Dalman, R. L., Baker, L. C. 2013; 57 (6): 1519-1523 e1

  Abstract

  Abdominal aortic aneurysm (AAA) screening remains largely underutilized in the U.S., and it is likely that the proportion of patients with aneurysms requiring prompt treatment is much higher compared with well-screened populations. The goals of this study were to determine the proportion of AAAs that required prompt repair after diagnostic abdominal imaging for U.S. Medicare beneficiaries and to identify patient and hospital factors contributing to early vs late diagnosis of AAA.Data were extracted from Medicare claims records for patients at least 65 years old with complete coverage for 2 years who underwent intact AAA repair from 2006 to 2009. Preoperative ultrasound and computed tomography was tabulated from 2002 to repair. We defined early diagnosis of AAA as a patient with a time interval of greater than 6 months between the first imaging examination and the index procedure, and late diagnosis as patients who underwent the index procedure within 6 months of the first imaging examination.Of 17,626 patients who underwent AAA repair, 14,948 met inclusion criteria. Mean age was 77.5 ± 6.1 years. Early diagnosis was identified for 60.6% of patients receiving AAA repair, whereas 39.4% were repaired after a late diagnosis. Early diagnosis rates increased from 2006 to 2009 (59.8% to 63.4%; P < .0001) and were more common for intact repair compared with repair after rupture (62.9% vs 35.1%; P < .0001) and for women compared with men (66.3% vs 59.0%; P < .0001). On multivariate analysis, repair of intact vs ruptured AAAs (odds ratio, 3.1; 95% confidence interval, 2.7-3.6) and female sex (odds ratio, 1.4; 95% confidence interval, 1.3-1.5) remained the strongest predictors of surveillance. Although intact repairs were more likely to be diagnosed early, over one-third of patients undergoing repair for ruptured AAAs received diagnostic abdominal imaging greater than 6 months prior to surgery.Despite advances in screening practices, significant missed opportunities remain in the U.S. Medicare population for improving AAA care. It remains common for AAAs to be diagnosed when they are already at risk for rupture. In addition, a significant proportion of patients with early imaging rupture prior to repair. Our findings suggest that improved mechanisms for observational management are needed to ensure optimal preoperative care for patients with AAAs.

  View details for DOI 10.1016/j.jvs.2012.12.034

  View details for PubMedID 23414696

• VEGF-A Neutralization Suppresses Experimental Abdominal Aortic Aneurysm (AAA) Formation Vascular Annual Meeting of the Society-for-Vascular-Surgery (SVS) Glover, K. J., Xu, B., Iida, Y., Xuan, H., Tanaka, H., Wang, W., Fujimura, N., Gerritsen, M., Dalman, R. L. MOSBY-ELSEVIER. 2013: 84S–84S

  View details for Web of Science ID 000318685300162

• Implementing Toyota Production System Practices Improves Efficiency of Patient Care in an Academic Vascular Practice Vascular Annual Meeting of the Society-for-Vascular-Surgery (SVS) Mell, M. W., Seshadri, S. B., Kwong, T., Dalman, R. L. MOSBY-ELSEVIER. 2013: 96S–96S

  View details for Web of Science ID 000318685300186

• Inhibition of Hypoxia Inducible Factor (HIF)-1 alpha Suppresses Formation and Progression of Experimental Abdominal Aortic Aneurysms (AAAs) Vascular Annual Meeting of the Society-for-Vascular-Surgery (SVS) Wang, W., Xu, B., Xuan, H., Tanaka, H., Rouer, M., Glover, K. J., Fujimura, N., Hu, X., Gerritsen, M., Michie, S. A., Dalman, R. L. MOSBY-ELSEVIER. 2013: 83S–84S

  View details for Web of Science ID 000318685300161

• Peptide inhibitor of CXCL4-CCL5 heterodimer formation, MKEY, inhibits experimental aortic aneurysm initiation and progression. Arteriosclerosis, thrombosis, and vascular biology Iida, Y., Xu, B., Xuan, H., Glover, K. J., Tanaka, H., Hu, X., Fujimura, N., Wang, W., Schultz, J. R., Turner, C. R., Dalman, R. L. 2013; 33 (4): 718-726

  Abstract

  Macrophages are critical contributors to abdominal aortic aneurysm (AAA) disease. We examined the ability of MKEY, a peptide inhibitor of CXCL4-CCL5 interaction, to influence AAA progression in murine models.AAAs were created in 10-week-old male C57BL/6J mice by transient infrarenal aortic porcine pancreatic elastase infusion. Mice were treated with MKEY via intravenous injection either (1) before porcine pancreatic elastase infusion or (2) after aneurysm initiation. Immunostaining demonstrated CCL5 and CCR5 expression on aneurysmal aortae and mural monocytes/macrophages, respectively. MKEY treatment partially inhibited migration of adaptively transferred leukocytes into aneurysmal aortae in recipient mice. Although all vehicle-pretreated mice developed AAAs, aneurysms formed in only 60% (3/5) and 14% (1/7) of mice pretreated with MKEY at 10 and 20 mg/kg, respectively. MKEY pretreatment reduced aortic diameter enlargement, preserved medial elastin fibers and smooth muscle cells, and attenuated mural macrophage infiltration, angiogenesis, and aortic metalloproteinase 2 and 9 expression after porcine pancreatic elastase infusion. MKEY initiated after porcine pancreatic elastase infusion also stabilized or reduced enlargement of existing AAAs. Finally, MKEY treatment was effective in limiting AAA formation after angiotensin II infusion in apolipoprotein E-deficient mice.MKEY suppresses AAA formation and progression in 2 complementary experimental models. Peptide inhibition of CXCL4-CCL5 interactions may represent a viable translational strategy to limit progression of human AAA disease.

  View details for DOI 10.1161/ATVBAHA.112.300329

  View details for PubMedID 23288157

  View details for PubMedCentralID PMC4158029

• Peptide Inhibitor of CXCL4-CCL5 Heterodimer Formation, MKEY, Inhibits Experimental Aortic Aneurysm Initiation and Progression ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY Iida, Y., Xu, B., Xuan, H., Glover, K. J., Tanaka, H., Hu, X., Fujimura, N., Wang, W., Schultz, J. R., Turner, C. R., Dalman, R. L. 2013; 33 (4): 718-U171

  View details for DOI 10.1161/ATVBAHA.112.300329

  View details for Web of Science ID 000316110400012

  View details for PubMedID 23288157

• Why Calls for More Routine Carotid Stenting Are Currently Inappropriate An International, Multispecialty, Expert Review and Position Statement STROKE Abbott, A. L., Adelman, M. A., Alexandrov, A. V., Barber, P. A., Barnett, H. J., Beard, J., Bell, P., Bjorck, M., Blacker, D., Bonati, L. H., Brown, M. M., Buckley, C. J., Cambria, R. P., Castaldo, J. E., Comerota, A. J., Connolly, E. S., Dalman, R. L., Davies, A. H., Eckstein, H., Faruqi, R., Feasby, T. E., Fraedrich, G., Gloviczki, P., Hankey, G. J., Harbaugh, R. E., Heldenberg, E., Hennerici, M. G., Hill, M. D., Kleinig, T. J., Mikhailidis, D. P., Moore, W. S., Naylor, R., Nicolaides, A., Paraskevas, K. I., Pelz, D. M., Prichard, J. W., Purdie, G., Ricco, J., Ringleb, P. A., Riles, T., Rothwell, P. M., Sandercock, P., Sillesen, H., Spence, J. D., Spinelli, F., Sturm, J., Tan, A., Thapar, A., Veith, F. J., Wijeratne, T., Zhou, W. 2013; 44 (4): 1186-1190

  View details for DOI 10.1161/STROKEAHA.111.000261

  View details for Web of Science ID 000316673900056

  View details for PubMedID 23512977

• The Vascular Research Initiatives Conference and over 25 years of conversations on the science of vascular disease JOURNAL OF VASCULAR SURGERY Curci, J. A., Kraiss, L., Dalman, R. L., Daugherty, A., Thompson, R. W., Dardik, A. 2013; 57 (2): 501-507

  View details for DOI 10.1016/j.jvs.2012.10.013

  View details for Web of Science ID 000313750800028

  View details for PubMedID 23337860

  View details for PubMedCentralID PMC3553505

• A Clinical Evaluation of Statin Pleiotropy: Statins Selectively and Dose-Dependently Reduce Vascular Inflammation PLOS ONE van der Meij, E., Koning, G. G., Vriens, P. W., Peeters, M. F., Meijer, C. A., Kortekaas, K. E., Dalman, R. L., van Bockel, J. H., Hanemaaijer, R., Kooistra, T., Kleemann, R., Lindeman, J. H. 2013; 8 (1)

  Abstract

  Statins are thought to reduce vascular inflammation through lipid independent mechanisms. Evaluation of such an effect in atherosclerotic disease is complicated by simultaneous effects on lipid metabolism. Abdominal aortic aneurysms (AAA) are part of the atherosclerotic spectrum of diseases. Unlike atherosclerotic occlusive disease, AAA is not lipid driven, thus allowing direct evaluation of putative anti-inflammatory effects. The anti-inflammatory potency of increasing doses (0, 20 or 40 mg/day) simvastatin or atorvastatin was evaluated in 63 patients that were at least 6 weeks on statin therapy and who underwent open AAA repair. A comprehensive analysis using immunohistochemistry, mRNA and protein analyses was applied on aortic wall samples collected during surgery. The effect of statins on AAA growth was analyzed in a separate prospective study in incorporating 142 patients. Both statins equally effectively and dose-dependently reduced aortic wall expression of NFκB regulated mediators (i.e. IL-6 (P<0.001) and MCP-1 (P<0.001)); shifted macrophage polarization towards a M2 phenotype (P<0.0003); selectively reduced macrophage-related markers such as cathepsin K and S (P<0.009 and 0.0027 respectively), and ALOX5 (P<0.0009), and reduced vascular wall NFκB activity (40 mg/day group, P<0.016). No effect was found on other cell types. Evaluation of the clinical efficacy of statins to reduce AAA progression did not indicate an effect of statins on aneurysm growth (P<0.337). Hence, in the context of AAA the clinical relevance of statins pleiotropy appears minimal.

  View details for DOI 10.1371/journal.pone.0053882

  View details for Web of Science ID 000314019100035

  View details for PubMedID 23349755

• Loss of CDKN2B promotes p53-dependent smooth muscle cell apoptosis and aneurysm formation. Arteriosclerosis, thrombosis, and vascular biology Leeper, N. J., Raiesdana, A., Kojima, Y., Kundu, R. K., Cheng, H., Maegdefessel, L., Toh, R., Ahn, G., Ali, Z. A., Anderson, D. R., Miller, C. L., Roberts, S. C., Spin, J. M., de Almeida, P. E., Wu, J. C., Xu, B., Cheng, K., Quertermous, M., Kundu, S., Kortekaas, K. E., Berzin, E., Downing, K. P., Dalman, R. L., Tsao, P. S., Schadt, E. E., Owens, G. K., Quertermous, T. 2013; 33 (1): e1-e10

  Abstract

  Genomewide association studies have implicated allelic variation at 9p21.3 in multiple forms of vascular disease, including atherosclerotic coronary heart disease and abdominal aortic aneurysm. As for other genes at 9p21.3, human expression quantitative trait locus studies have associated expression of the tumor suppressor gene CDKN2B with the risk haplotype, but its potential role in vascular pathobiology remains unclear.Here we used vascular injury models and found that Cdkn2b knockout mice displayed the expected increase in proliferation after injury, but developed reduced neointimal lesions and larger aortic aneurysms. In situ and in vitro studies suggested that these effects were attributable to increased smooth muscle cell apoptosis. Adoptive bone marrow transplant studies confirmed that the observed effects of Cdkn2b were mediated through intrinsic vascular cells and were not dependent on bone marrow-derived inflammatory cells. Mechanistic studies suggested that the observed increase in apoptosis was attributable to a reduction in MDM2 and an increase in p53 signaling, possibly due in part to compensation by other genes at the 9p21.3 locus. Dual inhibition of both Cdkn2b and p53 led to a reversal of the vascular phenotype in each model.These results suggest that reduced CDKN2B expression and increased smooth muscle cell apoptosis may be one mechanism underlying the 9p21.3 association with aneurysmal disease.

  View details for DOI 10.1161/ATVBAHA.112.300399

  View details for PubMedID 23162013

  View details for PubMedCentralID PMC3569043

• Loss of CDKN2B Promotes p53-Dependent Smooth Muscle Cell Apoptosis and Aneurysm Formation ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY Leeper, N. J., Raiesdana, A., Kojima, Y., Kundu, R. K., Cheng, H., Maegdefessel, L., Toh, R., Ahn, G., Ali, Z. A., Anderson, D. R., Miller, C. L., Roberts, S. C., Spin, J. M., de Almeida, P. E., Wu, J. C., Xu, B., Cheng, K., Quertermous, M., Kundu, S., Kortekaas, K. E., Berzin, E., Downing, K. P., Dalman, R. L., Tsao, P. S., Schadt, E. E., Owens, G. K., Quertermous, T. 2013; 33 (1): E1-?

  Abstract

  Genomewide association studies have implicated allelic variation at 9p21.3 in multiple forms of vascular disease, including atherosclerotic coronary heart disease and abdominal aortic aneurysm. As for other genes at 9p21.3, human expression quantitative trait locus studies have associated expression of the tumor suppressor gene CDKN2B with the risk haplotype, but its potential role in vascular pathobiology remains unclear.Here we used vascular injury models and found that Cdkn2b knockout mice displayed the expected increase in proliferation after injury, but developed reduced neointimal lesions and larger aortic aneurysms. In situ and in vitro studies suggested that these effects were attributable to increased smooth muscle cell apoptosis. Adoptive bone marrow transplant studies confirmed that the observed effects of Cdkn2b were mediated through intrinsic vascular cells and were not dependent on bone marrow-derived inflammatory cells. Mechanistic studies suggested that the observed increase in apoptosis was attributable to a reduction in MDM2 and an increase in p53 signaling, possibly due in part to compensation by other genes at the 9p21.3 locus. Dual inhibition of both Cdkn2b and p53 led to a reversal of the vascular phenotype in each model.These results suggest that reduced CDKN2B expression and increased smooth muscle cell apoptosis may be one mechanism underlying the 9p21.3 association with aneurysmal disease.

  View details for DOI 10.1161/ATVBAHA.112.300399

  View details for Web of Science ID 000312392500001

  View details for PubMedID 23162013

  View details for PubMedCentralID PMC3569043

• Efficacy and Mechanism of Angiotensin II Receptor Blocker Treatment in Experimental Abdominal Aortic Aneurysms PLOS ONE Iida, Y., Xu, B., Schultz, G. M., Chow, V., White, J. J., Sulaimon, S., Hezi-Yamit, A., Peterson, S. R., Dalman, R. L. 2012; 7 (12)

  Abstract

  Despite the importance of the renin-angiotensin (Ang) system in abdominal aortic aneurysm (AAA) pathogenesis, strategies targeting this system to prevent clinical aneurysm progression remain controversial and unproven. We compared the relative efficacy of two Ang II type 1 receptor blockers, telmisartan and irbesartan, in limiting experimental AAAs in distinct mouse models of aneurysm disease.AAAs were induced using either 1) Ang II subcutaneous infusion (1000 ng/kg/min) for 28 days in male ApoE(-/-) mice, or 2) transient intra-aortic porcine pancreatic elastase infusion in male C57BL/6 mice. One week prior to AAA creation, mice started to daily receive irbesartan (50 mg/kg), telmisartan (10 mg/kg), fluvastatin (40 mg/kg), bosentan (100 mg/kg), doxycycline (100 mg/kg) or vehicle alone. Efficacy was determined via serial in vivo aortic diameter measurements, histopathology and gene expression analysis at sacrifice. Aortic aneurysms developed in 67% of Ang II-infused ApoE(-/-) mice fed with standard chow and water alone (n = 15), and 40% died of rupture. Strikingly, no telmisartan-treated mouse developed an AAA (n = 14). Both telmisartan and irbesartan limited aneurysm enlargement, medial elastolysis, smooth muscle attenuation, macrophage infiltration, adventitial neocapillary formation, and the expression of proteinases and proinflammatory mediators. Doxycycline, fluvastatin and bosentan did not influence aneurysm progression. Telmisartan was also highly effective in intra-aortic porcine pancreatic elastase infusion-induced AAAs, a second AAA model that did not require exogenous Ang II infusion.Telmisartan suppresses experimental aneurysms in a model-independent manner and may prove valuable in limiting clinical disease progression.

  View details for DOI 10.1371/journal.pone.0049642

  View details for Web of Science ID 000312104700009

  View details for PubMedID 23226500

• A comparison of 0+5 versus 5+2 applicants to vascular surgery training programs 26th Annual Meeting of the Western-Vascular-Society Zayed, M. A., Dalman, R. L., Lee, J. T. MOSBY-ELSEVIER. 2012: 1448–52

  Abstract

  The new integrated 0 + 5 vascular surgery (VS) training paradigm introduced in 2007 required program directors and faculty to reconsider recruiting methods and exposure of medical students to VS. As a means to identify variables important for recruitment of 0 + 5 VS applicants, we sought to analyze national 0 + 5 VS residency application trends and to compare medical school demographics of applicants to both our 0 + 5 residency and 5 + 2 fellowship programs.Electronic Residency Application Service and National Resident Matching Program online public databases were queried to evaluate nationwide trends in the number of applicants to integrated VS residency programs between 2007 and 2010. Demographic data from Electronic Residency Application Service applications submitted to our institution's 0 + 5 and 5 + 2 VS training programs during the same time period were reviewed.From 2008 to 2011, there were 190 applicants to our 0 + 5 VS residency program and 161 applicants to our 5 + 2 fellowship program, with 127 (66.8%) and 122 (75.8%) being United States medical graduates, respectively. Annual application volume to our programs over these years remained stable for both training pathways (range, 39-49 for 0 + 5 integrated; range, 39-43 for 5 + 2 traditional). Nationally, applications to 0 + 5 programs increased sixfold over the same time period (52 in 2007 to 340 applicants in 2010; P < .001), far exceeding the available training positions. Compared with applicants to the 5 + 2 VS fellowships, medical students applying to the 0 + 5 programs are more likely to be female, be slightly older, have additional postgraduate degrees and publications, have higher United States Medical Licensure Examination test scores, and are more likely to be in the top quartile of their medical school class.Nationwide interest in the 0 + 5 vascular surgery residency training paradigm continues to significantly increase. Significant differences exist between the cohorts of 0 + 5 residency and 5 + 2 fellowship program applicants at the completion of medical school, suggesting that 0 + 5 VS residency programs are attracting a different medical student population to the VS specialty. VS program directors should continue to foster interest in this new applicant pool through early exposure, mentorship, and extracurricular research activities.

  View details for DOI 10.1016/j.jvs.2012.05.083

  View details for Web of Science ID 000310428200047

  View details for PubMedID 22857814

• No increased mortality with early aortic aneurysm disease 26th Annual Meeting of the Western-Vascular-Society Mell, M., White, J. J., Hill, B. B., Hastie, T., Dalman, R. L. MOSBY-ELSEVIER. 2012: 1246–51

  Abstract

  In addition to increased risks for aneurysm-related death, previous studies have determined that all-cause mortality in abdominal aortic aneurysm (AAA) patients is excessive and equivalent to that associated with coronary heart disease. These studies largely preceded the current era of coronary heart disease risk factor management, however, and no recent study has examined contemporary mortality associated with early AAA disease (aneurysm diameter between 3 and 5 cm). As part of an ongoing natural history study of AAA, we report the mortality risk associated with presence of early disease.Participants were recruited from three distinct health care systems in Northern California between 2006 and 2011. Aneurysm diameter, demographic information, comorbidities, medication history, and plasma for biomarker analysis were collected at study entry. Survival status was determined at follow-up. Data were analyzed with t-tests or χ(2) tests where appropriate. Freedom from death was calculated via Cox proportional hazards modeling; the relevance of individual predictors on mortality was determined by log-rank test.The study enrolled 634 AAA patients; age 76.4 ± 8.0 years, aortic diameter 3.86 ± 0.7 cm. Participants were mostly male (88.8%), not current smokers (81.6%), and taking statins (76.7%). Mean follow-up was 2.1 ± 1.0 years. Estimated 1- and 3-year survival was 98.2% and 90.9%, respectively. Factors independently associated with mortality included larger aneurysm size (hazard ratio, 2.12; 95% confidence interval, 1.26-3.57 for diameter >4.0 cm) and diabetes (hazard ratio, 2.24; 95% confidence interval, 1.12-4.47). After adjusting for patient-level factors, health care system independently predicted mortality.Contemporary all-cause mortality for patients with early AAA disease is lower than that previously reported. Further research is warranted to determine important factors that contribute to improved survival in early AAA disease.

  View details for DOI 10.1016/j.jvs.2012.04.023

  View details for Web of Science ID 000310428200007

  View details for PubMedID 22832264

• Standardization of outcome measures in clinical trials of pharmacological treatment for abdominal aortic aneurysm. Expert review of cardiovascular therapy Wang, X. L., Thompson, M. M., Dole, W. P., Dalman, R. L., Zalewski, A. 2012; 10 (10): 1251-1260

  Abstract

  An abdominal aortic aneurysm (AAA) is a common aortic wall disease with an increased prevalence in the elderly population (4-8% for those aged >65 years). Many AAAs are slow growing and remain insidious. Current standard of care for patients with small AAAs (<49 mm) is surveillance, with interventional therapy (open surgical repair or endovascular aneurysm repair) recommended for large (>50-55 mm), rapidly growing (>10 mm/year) or symptomatic AAAs. Although open surgical repair or endovascular aneurysm repair are effective, significant short- and long-term postoperative morbidity and mortality occurs. Currently, there is no pharmacological treatment specific for AAA; the need for the development of targeted pharmacological therapies based on clinically relevant and feasible outcomes acceptable to the medical community, regulatory agencies and third-party payers is high. A consensus on such end points will be critical to accelerating the development of pharmacological agents to prevent formation, arrest the expansion and reduce the rupture risk of AAA.

  View details for DOI 10.1586/erc.12.128

  View details for PubMedID 23113642

• Long-term results after accessory renal artery coverage during endovascular aortic aneurysm repair 26th Annual Meeting of the Western-Vascular-Society Greenberg, J. I., Dorsey, C., Dalman, R. L., Lee, J. T., Harris, E. J., Hernandez-Boussard, T., Mell, M. W. MOSBY-ELSEVIER. 2012: 291–97

  Abstract

  Current information regarding coverage of accessory renal arteries (ARAs) during endovascular aneurysm repair (EVAR) is based on small case series with limited follow-up. This study evaluates the outcomes of ARA coverage in a large contemporary cohort.Consecutive EVAR data from January 2004 to August 2010 were collected in a prospective database at a University Hospital. Patient and aneurysm-related characteristics, imaging studies, and ARA coverage versus preservation were analyzed. Volumetric analysis of three-dimensional reconstruction computed tomography scans was used to assess renal infarction volume extent. Long-term renal function and overall technical success of aneurysm exclusion were compared.A cohort of 426 EVARs was identified. ARAs were present in 69 patients with a mean follow-up of 27 months (range, 1 to 60 months). Forty-five ARAs were covered in 40 patients; 29 patients had intentional ARA preservation. Patient and anatomic characteristics were similar between groups except that ARA coverage patients had shorter aneurysm necks (P = .03). Renal infarctions occurred in 84% of kidneys with covered ARAs. There was no significant deterioration in long-term glomerular filtration rate when compared with patients in the control group. No difference in the rate of endoleak, secondary procedures, or the requirement for antihypertensive medications was found.This study is the largest to date with the longest follow-up relating to ARA coverage. Contrary to previous reports, renal infarction after ARA coverage is common. Nevertheless, coverage is well tolerated based upon preservation of renal function without additional morbidity. These results support the long-term safety of ARA coverage for EVAR when necessary.

  View details for DOI 10.1016/j.jvs.2012.01.049

  View details for Web of Science ID 000307160400002

  View details for PubMedID 22480767

• Fenestrate What You Can't Snorkel? ANNALS OF VASCULAR SURGERY Zayed, M. A., Chowdhury, M., Casey, K., Dalman, R. L., Lee, J. T. 2012; 26 (5)

  Abstract

  Although challenging proximal necks have limited the utility of standard endovascular aneurysm repair (EVAR) devices, sophisticated endovascular techniques have evolved in recent years for the repair of juxtarenal abdominal aortic aneurysms (AAAs). Among these techniques, snorkel or chimney EVAR (sn-EVAR) and fenestrated EVAR (f-EVAR) have emerged as options for repairing anatomic high-risk AAAs. Unfortunately, in the United States, except in the context of a clinical trial or physician-sponsored device exemption, limited long-term data exist on the treatment of juxta- and suprarenal AAAs with either sn-EVAR or f-EVAR. Owing to these limitations, comparison of these two techniques is challenging, and we sought to describe a case when one was favored over the other.A 72-year-old man presented with an enlarging, asymptomatic, juxtarenal fusiform AAA (5.9 cm), a moderately enlarged right common iliac artery (2.8 cm), a history of oxygen-dependent chronic obstructive pulmonary disease, and a previous right nephrectomy. An initial sn-EVAR was attempted but was unsuccessful owing to the inability to deliver the "snorkel" covered stent via a brachial approach because of renal ostial stenosis and cephalad angulation of the patient's left renal artery. A subsequent f-EVAR approach was successfully used to repair the juxtarenal AAA while preserving adequate renal artery blood flow. Two-year postoperative follow-up demonstrated a stable endovascular repair without endoleaks, a shrinking aneurysm sac, and stable renal function.The sn-EVAR configuration in this case report was precluded by cephalad renal angulation, and the AAA was instead repaired using an f-EVAR approach, with good 2-year follow-up outcomes. The sn-EVAR strategy requires downward pointing renal arteries in addition to adequate brachial/axillary artery access dimensions to facilitate successful repair. With improving techniques and technology for either approach, anatomic specifications and indications for these advanced EVAR strategies will need to be delineated.

  View details for DOI 10.1016/j.avsg.2011.08.027

  View details for Web of Science ID 000304901500027

  View details for PubMedID 22664290

• RGD-Conjugated Human Ferritin Nanoparticles for Imaging Vascular Inflammation and Angiogenesis in Experimental Carotid and Aortic Disease MOLECULAR IMAGING AND BIOLOGY Kitagawa, T., Kosuge, H., Uchida, M., Dua, M. M., Iida, Y., Dalman, R. L., Douglas, T., McConnell, M. V. 2012; 14 (3): 315-324

  Abstract

  Inflammation and angiogenesis are important contributors to vascular disease. We evaluated imaging both of these biological processes, using Arg-Gly-Asp (RGD)-conjugated human ferritin nanoparticles (HFn), in experimental carotid and abdominal aortic aneurysm (AAA) disease.Macrophage-rich carotid lesions were induced by ligation in hyperlipidemic and diabetic FVB mice (n = 16). AAAs were induced by angiotensin II infusion in apoE(-/-) mice (n=10). HFn, with or without RGD peptide, was labeled with Cy5.5 and injected intravenously for near-infrared fluorescence imaging.RGD-HFn showed significantly higher signal than HFn in diseased carotids and AAAs relative to non-diseased regions, both in situ (carotid: 1.88 ± 0.30 vs. 1.17 ± 0.10, p = 0.04; AAA: 2.59 ± 0.24 vs. 1.82 ± 0.16, p = 0.03) and ex vivo. Histology showed RGD-HFn colocalized with macrophages in carotids and both macrophages and neoangiogenesis in AAA lesions.RGD-HFn enhances vascular molecular imaging by targeting both vascular inflammation and angiogenesis, and allows more comprehensive detection of high-risk atherosclerotic and aneurysmal vascular diseases.

  View details for DOI 10.1007/s11307-011-0495-1

  View details for Web of Science ID 000303884400006

  View details for PubMedID 21638084

• Angiogenesis Inhibitor Sunitinib Suppresses the Formation and Progression of Experimental Abdominal Aortic Aneurysm William J. Von Liebig Forum at the Rapid Session of the Vascular Annual Meeting of the Society-for-Vascular-Surgery (SVS) / Peripheral-Vascular-Surgery-Society Session Iida, Y., Xu, B., Hu, X., Chow, V., Yuan, R., Gerritsen, M., Ogino, H., Dalman, R. L. MOSBY-ELSEVIER. 2012: 81–82

  View details for Web of Science ID 000304398900158

• Factors Impacting Follow-up Care after Placement of Temporary Inferior Vena Cava Filters William J. Von Liebig Forum at the Rapid Session of the Vascular Annual Meeting of the Society-for-Vascular-Surgery (SVS) / Peripheral-Vascular-Surgery-Society Session Gyang, E., Zayed, M., Harris, E. J., Lee, J. T., Dalman, R. L., Mell, M. W. MOSBY-ELSEVIER. 2012: 60–60

  View details for Web of Science ID 000304398900115

• See One, Sim One, Do One, Teach One: Results of a Prospective Randomized Trial of Endovascular Skills Training for Surgical Residents William J. Von Liebig Forum at the Rapid Session of the Vascular Annual Meeting of the Society-for-Vascular-Surgery (SVS) / Peripheral-Vascular-Surgery-Society Session Lee, J. T., Peruzzaro, A., Krummel, T., Dalman, R. L. MOSBY-ELSEVIER. 2012: 27–27

  View details for Web of Science ID 000304398900047

• Selective Use of Percutaneous Endovascular Aneurysm Repair in Women Leads to Fewer Groin Complications 35th Annual Spring Meeting of the Peripheral-Vascular-Surgery-Society Al-Khatib, W. K., Zayed, M. A., Harris, E. J., Dalman, R. L., Lee, J. T. ELSEVIER SCIENCE INC. 2012: 476–82

  Abstract

  Endovascular aneurysm repair (EVAR) in women is often technically limited by smaller access vessel anatomy, particularly at the femoral and iliac artery levels. Percutaneous femoral artery access and closure using the "Preclose" technique (PERC) is a less invasive alternative to open surgical femoral arterial exposure and has been reported to be technically feasible, particularly in male cohorts. The purpose of this study was to evaluate the efficacy and access-related outcomes of PERC in women undergoing EVAR.We identified female patients in a prospectively maintained EVAR database from 2000 to 2009. An all-percutaneous approach was adopted in 2007 if technically feasible, based on preoperative computed tomography angiogram criteria including a femoral diameter >7 mm, <25% posterior plaque and lack of circumferential calcification/disease. All percutaneous EVAR procedures were performed using two Perclose Proglide devices in a standardized manner for sheath sizes ranging between 12F and 26F.In period 1 (2000-2006), most cases were performed with open femoral exposure. In period 2 (2007-2009), our group adopted a percutaneous-first approach. Of 736 EVARs performed during the study period, 120 (16.3%) were in women, leading to 178 femoral arteries requiring large sheath access. Period 1 included 90 women and period 2 included 30 women who were evaluated for percutaneous access. During period 2, of the 47 eligible femoral arteries for possible PERC, 24 (51%) met appropriate criteria, and the Preclose technique was employed. The remaining 23 femoral arteries during period 2 were accessed with surgical exposure (OPEN). Technical success rate of PERC in period 2 was 96%, with one device pulling through a thin anterior arterial wall requiring open femoral conversion. During period 2, the OPEN cohort had a higher rate of total wound complications compared with PERC (34.8% vs. 8.3%, P = 0.02), including hematomas (8.7% vs. 0%), wound breakdowns (8.7% vs. 0%), and pseudoaneurysms (4.3% vs. 0%). There were two cases of femoral artery thrombosis in the PERC group requiring repair in the immediate postoperative period; however, this was not significantly different compared with the OPEN group (8.7% vs. 8.3%).Selective percutaneous access of the femoral arteries for EVAR is safe and effective in the female population, with fewer wound complications than open exposure. Approximately one-half of femoral arteries in women are eligible for PERC access, and complications can be limited with careful selection based on preoperative imaging.

  View details for DOI 10.1016/j.avsg.2011.11.026

  View details for Web of Science ID 000303110300005

  View details for PubMedID 22437069

• Determinants of Adverse Events in Vascular Surgery JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS Hernandez-Boussard, T., McDonald, K. M., Morton, J. M., Dalman, R. L., Bech, F. R. 2012; 214 (5): 788-797

  Abstract

  Patient safety is a national priority. Patient Safety Indicators (PSIs) monitor potential adverse events during hospital stays. Surgical specialty PSI benchmarks do not exist, and are needed to account for differences in the range of procedures performed, reasons for the procedure, and differences in patient characteristics. A comprehensive profile of adverse events in vascular surgery was created.The Nationwide Inpatient Sample was queried for 8 vascular procedures using ICD-9-CM codes from 2005 to 2009. Factors associated with PSI development were evaluated in univariate and multivariate analyses.A total of 1,412,703 patients underwent a vascular procedure and a PSI developed in 5.2%. PSIs were more frequent in female, nonwhite patients with public payers (p < 0.01). Patients at mid and low-volume hospitals had greater odds of developing a PSI (odds ratio [OR] = 1.17; 95% CI, 1.10-1.23 and OR = 1.69; 95% CI, 1.53-1.87). Amputations had highest PSI risk-adjusted rate and carotid endarterectomy and endovascular abdominal aortic aneurysm repair had lower risk-adjusted rate (p < 0.0001). PSI risk-adjusted rate increased linearly by severity of patient indication: claudicants (OR = 0.40; 95% CI, 0.35-0.46), rest pain patients (OR = 0.78; 95% CI, 0.69-0.90), ulcer (OR = 1.20; 95% CI, 1.07-1.34), and gangrene patients (OR = 1.85; 95% CI, 1.66-2.06).Patient safety events in vascular surgery were high and varied by procedure, with amputations and open abdominal aortic aneurysm repair having considerably more potential adverse events. PSIs were associated with black race, public payer, and procedure indication. It is important to note the overall higher rates of PSIs occurring in vascular patients and to adjust benchmarks for this surgical specialty appropriately.

  View details for DOI 10.1016/j.jamcollsurg.2012.01.045

  View details for Web of Science ID 000303724200009

  View details for PubMedID 22425449

• Early experience with the snorkel technique for juxtarenal aneurysms 26th Annual Meeting of the Western-Vascular-Society Lee, J. T., Greenberg, J. I., Dalman, R. L. MOSBY-ELSEVIER. 2012: 935–46

  Abstract

  The lack of readily available branched and fenestrated endovascular aneurysm repair (EVAR) options has created an opportunity for creative deployment of endograft components to treat juxtarenal aneurysms. We present our early experience with "snorkel" or "chimney" techniques in the endovascular management of complex aortic aneurysms.We retrospectively reviewed planned snorkel procedures for juxtarenal aneurysms performed from September 2009 to August 2011. Our standardized technique included axillary or brachial cutdown for delivery of covered snorkel stents and mostly percutaneous femoral access for the main body endograft.Fifty-six snorkel grafts were successfully placed in 28 consecutive patients (mean age, 75 years) with juxtarenal aneurysms. Mean aneurysm size was 64.8 mm (range, 53-87 mm). The snorkel configuration extended the proximal seal zone from an unsuitable infrarenal neck for standard EVAR (median diameter, 33.5 mm; length, 0.0 mm) to a median neck diameter of 24.5 mm and length of 18.0 mm. Five patients had unilateral renal snorkels, 17 had bilateral renal snorkels, and six had celiac/superior mesenteric artery/renal combinations. Technical success of snorkel placements was 98.2%, with loss of wire access leading to one renal stent deployment failure. Thirty-day mortality was 7.1%: one patient was readmitted 1 week postoperatively with pneumonia and died of sepsis; one patient died at 1 week of a right hemispheric stroke. Other major complications included perinephric hematomas, 7.1%; permanent hemodialysis, 3.6%; iliac artery injury requiring endoconduit placement, 3.6%; and brachial plexus nerve injury, 3.6%. Cardiac complications included self-limited arrhythmias (14.3%) and one non-Q-wave myocardial infarction (3.6%), with all recovering without coronary intervention. Mean follow-up was 10.7 months (range, 3-25 months). One patient died of nonaneurysmal-related causes at 3 months (89.3% survival). Postoperative imaging revealed one renal snorkel graft occlusion occurring at 3 months (98.2% overall primary patency). Seven (25%) early endoleaks were noted on the first follow-up computed tomography angiography: two type I, three type II, and two type III (25%), leading to one secondary intervention (3.6%) with bridging cuff placement (type III). The small type Ia endoleaks and other type III endoleak resolved at the 6-month scan. Mean sac regression at the latest follow-up was 7.3 mm. No aneurysm has enlarged on postoperative imaging.Early success with the snorkel technique for juxtarenal aneurysms has made it our procedure of choice for complex short-neck to no-neck EVAR. Although long-term follow-up is needed, the flexibility of the snorkel technique and lack of requirement for custom-built devices may make this approach more attractive than branched or fenestrated stent grafts.

  View details for DOI 10.1016/j.jvs.2011.11.041

  View details for Web of Science ID 000302145700006

  View details for PubMedID 22244859

• Bioluminescence and Magnetic Resonance Imaging of Macrophage Homing to Experimental Abdominal Aortic Aneurysms MOLECULAR IMAGING Miyama, N., Dua, M. M., Schultz, G. M., Kosuge, H., Terashima, M., Pisani, L. J., Dalman, R. L., McConnell, M. V. 2012; 11 (2): 126-134

  Abstract

  Macrophage infiltration is a prominent feature of abdominal aortic aneurysm (AAA) progression. We used a combined imaging approach with bioluminescence (BLI) and magnetic resonance imaging (MRI) to study macrophage homing and accumulation in experimental AAA disease. Murine AAAs were created via intra-aortic infusion of porcine pancreatic elastase. Mice were imaged over 14 days after injection of prepared peritoneal macrophages. For BLI, macrophages were from transgenic mice expressing luciferase. For MRI, macrophages were labeled with iron oxide particles. Macrophage accumulation during aneurysm progression was observed by in situ BLI and by in vivo 7T MRI. Mice were sacrificed after imaging for histologic analysis. In situ BLI (n  =  32) demonstrated high signal in the AAA by days 7 and 14, which correlated significantly with macrophage number and aortic diameter. In vivo 7T MRI (n  =  13) at day 14 demonstrated T₂* signal loss in the AAA and not in sham mice. Immunohistochemistry and Prussian blue staining confirmed the presence of injected macrophages in the AAA. BLI and MRI provide complementary approaches to track macrophage homing and accumulation in experimental AAAs. Similar dual imaging strategies may aid the study of AAA biology and the evaluation of novel therapies.

  View details for DOI 10.2310/7290.2011.00033

  View details for Web of Science ID 000307645900004

  View details for PubMedID 22469240

• MicroRNA-21 Blocks Abdominal Aortic Aneurysm Development and Nicotine-Augmented Expansion SCIENCE TRANSLATIONAL MEDICINE Maegdefessel, L., Azuma, J., Toh, R., Deng, A., Merk, D. R., Raiesdana, A., Leeper, N. J., Raaz, U., Schoelmerich, A. M., McConnell, M. V., Dalman, R. L., Spin, J. M., Tsao, P. S. 2012; 4 (122)

  Abstract

  Identification and treatment of abdominal aortic aneurysm (AAA) remains among the most prominent challenges in vascular medicine. MicroRNAs are crucial regulators of cardiovascular pathology and represent possible targets for the inhibition of AAA expansion. We identified microRNA-21 (miR-21) as a key modulator of proliferation and apoptosis of vascular wall smooth muscle cells during development of AAA in two established murine models. In both models (AAA induced by porcine pancreatic elastase or infusion of angiotensin II), miR-21 expression increased as AAA developed. Lentiviral overexpression of miR-21 induced cell proliferation and decreased apoptosis in the aortic wall, with protective effects on aneurysm expansion. miR-21 overexpression substantially decreased expression of the phosphatase and tensin homolog (PTEN) protein, leading to increased phosphorylation and activation of AKT, a component of a pro-proliferative and antiapoptotic pathway. Systemic injection of a locked nucleic acid-modified antagomir targeting miR-21 diminished the pro-proliferative impact of down-regulated PTEN, leading to a marked increase in the size of AAA. Similar results were seen in mice with AAA augmented by nicotine and in human aortic tissue samples from patients undergoing surgical repair of AAA (with more pronounced effects observed in smokers). Modulation of miR-21 expression shows potential as a new therapeutic option to limit AAA expansion and vascular disease progression.

  View details for DOI 10.1126/scitranslmed.3003441

  View details for Web of Science ID 000300952100004

  View details for PubMedID 22357537

• Inhibition of microRNA-29b reduces murine abdominal aortic aneurysm development JOURNAL OF CLINICAL INVESTIGATION Maegdefessel, L., Azuma, J., Toh, R., Merk, D. R., Deng, A., Chin, J. T., Raaz, U., Schoelmerich, A. M., Raiesdana, A., Leeper, N. J., McConnell, M. V., Dalman, R. L., Spin, J. M., Tsao, P. S. 2012; 122 (2): 497-506

  Abstract

  MicroRNAs (miRs) regulate gene expression at the posttranscriptional level and play crucial roles in vascular integrity. As such, they may have a role in modifying abdominal aortic aneurysm (AAA) expansion, the pathophysiological mechanisms of which remain incompletely explored. Here, we investigate the role of miRs in 2 murine models of experimental AAA: the porcine pancreatic elastase (PPE) infusion model in C57BL/6 mice and the AngII infusion model in Apoe-/- mice. AAA development was accompanied by decreased aortic expression of miR-29b, along with increased expression of known miR-29b targets, Col1a1, Col3a1, Col5a1, and Eln, in both models. In vivo administration of locked nucleic acid anti-miR-29b greatly increased collagen expression, leading to an early fibrotic response in the abdominal aortic wall and resulting in a significant reduction in AAA progression over time in both models. In contrast, overexpression of miR-29b using a lentiviral vector led to augmented AAA expansion and significant increase of aortic rupture rate. Cell culture studies identified aortic fibroblasts as the likely vascular cell type mediating the profibrotic effects of miR-29b modulation. A similar pattern of reduced miR-29b expression and increased target gene expression was observed in human AAA tissue samples compared with that in organ donor controls. These data suggest that therapeutic manipulation of miR-29b and its target genes holds promise for limiting AAA disease progression and protecting from rupture.

  View details for DOI 10.1172/JCI61598

  View details for Web of Science ID 000299765800016

  View details for PubMedID 22269326

• Cost Impact of Extension Cuff Utilization During Endovascular Aneurysm Repair 21st Annual Winter Meeting of the Peripheral-Vascular-Surgery-Society Chandra, V., Greenberg, J. I., Al-Khatib, W. K., Harris, E. J., Dalman, R. L., Lee, J. T. ELSEVIER SCIENCE INC. 2012: 86–92

  Abstract

  Modular stent-graft systems for endovascular aneurysm repair (EVAR) most often require two to three components, depending on the device. Differences in path lengths and availability of main body systems often require additional extensions for appropriate aneurysm exclusion. These additional devices usually result in added expenses and can affect the financial viability of an EVAR program within a hospital. The purpose of this study was to analyze the use of extensions during EVAR, focusing on incidence, clinical impact, and financial impact, as well as determining the associated cost differences between two- and three-component EVAR device systems.We reviewed available clinical data, images, and follow-up of 218 patients (203 males and 15 females, mean age: 74 ± 9 years) who underwent elective EVAR at a single academic center from 2004 to 2007. Patients were divided into two groups: patients undergoing EVAR using the standard number of pieces, that is, no extensions used (group A, n = 98), and those needing proximal or distal extensions during the index procedure (group B, n = 120).Both groups were similar in terms of demographics; preoperative characteristics, including aneurysm morphology; as well as intraoperative, postoperative, and midterm outcomes. Overall, 30-day operative mortality was 1.4%, with a mean follow-up of 24 months. Group A patients underwent repair with two-piece modular devices 41% of the time and three-piece systems 59% of the time, whereas group B patients underwent repair with two-piece modular systems 82% of the time and three-piece modular systems 18% of the time. The number of additional extensions per patient ranged from one to four (median: one piece). There was a 30% cost increase in overall mean device-related cost when using extensions versus the standard number of pieces (group A: $13,220 vs. group B: $17,107, p < 0.01).Clinical midterm aneurysm-related outcomes after EVAR in patients who required additional extensions was comparable with those treated with the standard number of pieces. An increased number of extensions led to increased costs and could have potentially been minimized with appropriate preoperative planning or device selection. Consideration should be made toward per-case pricing instead of per-piece pricing to further improve cost efficiency without compromising long-term patient outcomes.

  View details for DOI 10.1016/j.avsg.2011.10.003

  View details for Web of Science ID 000298325900011

  View details for PubMedID 22176878

• Endovascular Repair of Bilateral Iliac Artery Aneurysms in a Patient With Loeys-Dietz Syndrome 21st Annual Winter Meeting of the Peripheral-Vascular-Surgery-Society Casey, K., Zayed, M., Greenberg, J. I., Dalman, R. L., Lee, J. T. ELSEVIER SCIENCE INC. 2012

  Abstract

  Loeys-Dietz syndrome (LDS) is a rare congenital connective tissue disorder (CTD) caused by mutations in the gene encoding for transforming growth factor-β receptors I and II. This recently described syndrome is characterized by aortic aneurysms and dissections, arterial tortuosity, and spontaneous organ perforation. The technical feasibility of endovascular interventions, particularly endovascular aneurysm repair (EVAR), in CTDs is relatively unknown.A 38-year-old man presented with asymptomatic bilateral common iliac artery aneurysms measuring 5.3 cm on the right and 4.3 cm on the left. The patient had an extensive surgical and medical history, including a recently repaired Stanford type-A aortic dissection, total colectomy with end ileostomy for a colonic perforation, splenectomy for rupture, and cirrhosis secondary to chronic hepatitis C. The patient's CTD, multiple abdominal surgeries performed in the past, and ileostomy made him a poor candidate for open repair. We elected to offer him a complex endovascular repair and hoped to preserve his pelvic circulation by using "double-barrel" configuration of stent-grafts in the right iliac artery system. Successful deployment of the devices and repair of femoral access allowed routine discharge on postoperative day 2. At 6-month follow-up, the patient's pelvic circulation has been maintained, the aneurysms are excluded without endoleak, and sac regression has been shown.LDS is a rare connective tissue disorder characterized by vascular aneurysms and arterial tortuosity. When vascular reconstruction is necessary, open techniques are often preferred given the lack of data on endovascular procedures. In the present case, we report the first successful abdominal EVAR in a high-risk patient with LDS, providing excellent short-term results.

  View details for DOI 10.1016/j.avsg.2011.06.005

  View details for Web of Science ID 000298325900015

  View details for PubMedID 21835579

• Long-term impact of a preclinical endovascular skills course on medical student career choices 25th Annual Meeting of the Western-Vascular-Society Lee, J. T., Son, J. H., Chandra, V., Lilo, E., Dalman, R. L. MOSBY-ELSEVIER. 2011: 1193–1200

  Abstract

  Surging interest in the 0 + 5 integrated vascular surgery (VS) residency and successful recruitment of the top students in medical school requires early exposure to the field. We sought to determine the impact of a high-fidelity simulation-based preclinical endovascular skills course on medical student performance and ultimate career specialty choices.Fifty-two preclinical medical students enrolled in an 8-week VS elective course from 2007 to 2009. Students completed a baseline and postcourse survey and performed a renal angioplasty/stent procedure on an endovascular simulator (pretest). A curriculum consisting of didactic teaching covering peripheral vascular disease and weekly mentored simulator sessions concluded with a final graded procedure (posttest). Long-term follow-up surveys 1 to 3 years after course completion were administered to determine ultimate career paths of participants as well as motivating factors for career choice.Objective and subjective performance measured on the simulator and through structured global assessment scales improved in all students from pre- to posttest, particularly with regard to technical skill and overall procedural competency (P < .001). Prior to enrolling in the course, 9% of the students expressed high interest in VS, and after completing the course, this response nearly tripled in terms of seriously considering VS as a career option (P = .03). Overall interest postcourse in VS and procedural-based surgical specialties was nearly 90%. In long-term follow-up, 25% were still strongly considering integrated VS residencies, with other top career choices including surgical subspecialties (64%), radiology (10%), and cardiology (6%). Most respondents indicated major reasons for continued interest in VS were the ability to practice endovascular procedures on the simulator (92%) and mentorship from VS faculty (70%).Basic endovascular skills can be efficiently introduced through a simulation-based curriculum and lead to improved novice performance. Early exposure of preclinical medical students provides an effective teaching and recruitment tool for procedural-based fields, particularly surgical subspecialties. Mentored exposure to endovascular procedures on the simulator positively impacts long-term medical student attitudes toward vascular surgery and ultimate career choices.

  View details for DOI 10.1016/j.jvs.2011.04.052

  View details for Web of Science ID 000295562800042

  View details for PubMedID 21723068

• Transcriptional profiling and network analysis of the murine angiotensin II-induced abdominal aortic aneurysm PHYSIOLOGICAL GENOMICS Spin, J. M., Hsu, M., Azuma, J., Tedesco, M. M., Deng, A., Dyer, J. S., Maegdefessel, L., Dalman, R. L., Tsao, P. S. 2011; 43 (17): 993-1003

  Abstract

  We sought to characterize temporal gene expression changes in the murine angiotensin II (ANG II)-ApoE-/- model of abdominal aortic aneurysm (AAA). Aortic ultrasound measurements were obtained over the 28-day time-course. Harvested suprarenal aortic segments were evaluated with whole genome expression profiling at 7, 14, and 28 days using the Agilent Whole Mouse Genome microarray platform and Statistical Analysis of Microarrays at a false discovery rate of <1%. A group of angiotensin-treated mice experienced contained rupture (CR) within 7 days and were analyzed separately. Progressive aortic dilatation occurred throughout the treatment period. However, the numerous early expression differences between ANG II-treated and control were not sustained over time. Ontologic analysis revealed widespread upregulation of inflammatory, immune, and matrix remodeling genes with ANG II treatment, among other pathways such as apoptosis, cell cycling, angiogenesis, and p53 signaling. CR aneurysms displayed significant decreases in TGF-β/BMP-pathway signaling, MAPK signaling, and ErbB signaling genes vs. non-CR/ANG II-treated samples. We also performed literature-based network analysis, extracting numerous highly interconnected genes associated with aneurysm development such as Spp1, Myd88, Adam17 and Lox. 1) ANG II treatment induces extensive early differential expression changes involving abundant signaling pathways in the suprarenal abdominal aorta, particularly wide-ranging increases in inflammatory genes with aneurysm development. 2) These gene expression changes appear to dissipate with time despite continued growth, suggesting that early changes in gene expression influence disease progression in this AAA model, and that the aortic tissue adapts to prolonged ANG II infusion. 3) Network analysis identified nexus genes that may constitute aneurysm biomarkers or therapeutic targets.

  View details for DOI 10.1152/physiolgenomics.00044.2011

  View details for Web of Science ID 000294730000002

  View details for PubMedID 21712436

• No Increased Mortality with Early Aortic Aneurysm Disease Mell, M., White, J. J., Hill, B. B., Dalman, R. L. MOSBY-ELSEVIER. 2011: 591–91

  View details for Web of Science ID 000293814400078

• Early Experience with the Snorkel Technique for Juxtarenal Aneurysms: The Preferred Off-the-Shelf Solution for Challenging EVAR Anatomy? Lee, J. T., Greenberg, J. I., Dalman, R. L. MOSBY-ELSEVIER. 2011: 589–89

  View details for Web of Science ID 000293814400070

• Agreement between activity monitoring devices during home rehabilitation: a sub-study of the AAA stop trial Myers, J., Dupain, M., Vu, A., Powell, A., Smith, K., Dalman, R. OXFORD UNIV PRESS. 2011: 382–383

  View details for Web of Science ID 000208702703257

• Long-Term Results after Accessory Renal Artery Coverage during Endovascular Aortic Aneurysm Repair Greenberg, J. I., Dorsey, C., Dalman, R. L., Lee, J. T., Mell, M. W. MOSBY-ELSEVIER. 2011: 588–88

  View details for Web of Science ID 000293814400067

• Hemodynamic Changes Quantified in Abdominal Aortic Aneurysms with Increasing Exercise Intensity Using MR Exercise Imaging and Image-Based Computational Fluid Dynamics ANNALS OF BIOMEDICAL ENGINEERING Suh, G., Les, A. S., Tenforde, A. S., Shadden, S. C., Spilker, R. L., Yeung, J. J., Cheng, C. P., Herfkens, R. J., Dalman, R. L., Taylor, C. A. 2011; 39 (8): 2186-2202

  Abstract

  Abdominal aortic aneurysm (AAA) is a vascular disease resulting in a permanent, localized enlargement of the abdominal aorta. We previously hypothesized that the progression of AAA may be slowed by altering the hemodynamics in the abdominal aorta through exercise [Dalman, R. L., M. M. Tedesco, J. Myers, and C. A. Taylor. Ann. N.Y. Acad. Sci. 1085:92-109, 2006]. To quantify the effect of exercise intensity on hemodynamic conditions in 10 AAA subjects at rest and during mild and moderate intensities of lower-limb exercise (defined as 33 ± 10% and 63 ± 18% increase above resting heart rate, respectively), we used magnetic resonance imaging and computational fluid dynamics techniques. Subject-specific models were constructed from magnetic resonance angiography data and physiologic boundary conditions were derived from measurements made during dynamic exercise. We measured the abdominal aortic blood flow at rest and during exercise, and quantified mean wall shear stress (MWSS), oscillatory shear index (OSI), and particle residence time (PRT). We observed that an increase in the level of activity correlated with an increase of MWSS and a decrease of OSI at three locations in the abdominal aorta, and these changes were most significant below the renal arteries. As the level of activity increased, PRT in the aneurysm was significantly decreased: 50% of particles were cleared out of AAAs within 1.36 ± 0.43, 0.34 ± 0.10, and 0.22 ± 0.06 s at rest, mild exercise, and moderate exercise levels, respectively. Most of the reduction of PRT occurred from rest to the mild exercise level, suggesting that mild exercise may be sufficient to reduce flow stasis in AAAs.

  View details for DOI 10.1007/s10439-011-0313-6

  View details for Web of Science ID 000292268900008

  View details for PubMedID 21509633

  View details for PubMedCentralID PMC3362397

• Cardiopulmonary exercise testing in small abdominal aortic aneurysm: profile, safety, and mortality estimates EUROPEAN JOURNAL OF CARDIOVASCULAR PREVENTION & REHABILITATION Myers, J., Powell, A., Smith, K., Fonda, H., Dalman, R. L. 2011; 18 (3): 459-466

  Abstract

  Few data are available regarding exercise testing in patients with abdominal aortic aneurysm (AAA) disease. The purpose of this study was to evaluate safety and to characterize the hemodynamic and cardiopulmonary (CPX) response to exercise in a large group of patients with AAA.Three hundred and six patients with AAA ≥3.0 to ≤5.0 cm (mean 72 ± 8 years) underwent CPX as part of a randomized trial of exercise training. CPX and hemodynamic responses, ischemic events, rhythm disturbances, and risk estimates based on treadmill scores were quantified and compared to an age-matched group of 2155 veterans referred for exercise testing for clinical reasons.Peak VO(2) was similar between patients with AAA and the referral group (20.0 ± 6 ml/kg/min; 77 percent of age-predicted and 20.3 ± 7 ml/kg/min; 80 percent of age-predicted, respectively). The incidence of exercise-induced hypotension and hypertension was higher in AAA patients versus the referral group (2.9 and 3.6 percent vs <1.0 percent, p < 0.001), but there were no occurrences of ventricular tachycardia (≥3 beats) or other serious events in the AAA subjects. The Duke Treadmill Score and VA Treadmill Scores, which estimate annual cardiovascular events and all-cause mortality, respectively, were similar between groups.Patients with AAA have a slightly higher incidence of hyper- and hypotensive responses to exercise than age-matched referrals, but no serious events related to CPX occurred. AAA patients can undergo maximal CPX safely and have risk scores based on treadmill test results that are similar to age-matched referral subjects. These findings extend recent studies using sub-maximal evaluations to stratify risk in patients considered for surgery, and support the routine use of exercise testing for risk evaluation and the functional assessment of patients with AAA.

  View details for DOI 10.1177/1741826710389384

  View details for Web of Science ID 000291026100013

  View details for PubMedID 21450647

• Interactive Online Training Improves Trainee Test Performance in Vascular Surgery Vascular Annual Meeting of the Society-for-Vascular-Surgery Zayed, M. A., Casey, K., Lilo, E., Dalman, R. L., Lee, J. T. MOSBY-ELSEVIER. 2011: 99S–100S

  View details for Web of Science ID 000291410700192

• Influences of Aortic Motion and Curvature on Vessel Expansion in Murine Experimental Aneurysms ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY Goergen, C. J., Azuma, J., Barr, K. N., Magdefessel, L., Kallop, D. Y., Gogineni, A., Grewall, A., Weimer, R. M., Connolly, A. J., Dalman, R. L., Taylor, C. A., Tsao, P. S., Greve, J. M. 2011; 31 (2): 270-U102

  Abstract

  To quantitatively compare aortic curvature and motion with resulting aneurysm location, direction of expansion, and pathophysiological features in experimental abdominal aortic aneurysms (AAAs).MRI was performed at 4.7 T with the following parameters: (1) 3D acquisition for vessel geometry and (2) 2D cardiac-gated acquisition to quantify luminal motion. Male 24-week-old mice were imaged before and after AAA formation induced by angiotensin II (AngII)-filled osmotic pump implantation or infusion of elastase. AngII-induced AAAs formed near the location of maximum abdominal aortic curvature, and the leftward direction of expansion was correlated with the direction of suprarenal aortic motion. Elastase-induced AAAs formed in a region of low vessel curvature and had no repeatable direction of expansion. AngII significantly increased mean blood pressure (22.7 mm Hg, P<0.05), whereas both models showed a significant 2-fold decrease in aortic cyclic strain (P<0.05). Differences in patterns of elastin degradation and localization of fluorescent signal from protease-activated probes were also observed.The direction of AngII aneurysm expansion correlated with the direction of motion, medial elastin dissection, and adventitial remodeling. Anterior infrarenal aortic motion correlated with medial elastin degradation in elastase-induced aneurysms. Results from both models suggest a relationship between aneurysm pathological features and aortic geometry and motion.

  View details for DOI 10.1161/ATVBAHA.110.216481

  View details for Web of Science ID 000286376800010

  View details for PubMedID 21071686

  View details for PubMedCentralID PMC3024449

• Quantification of Particle Residence Time in Abdominal Aortic Aneurysms Using Magnetic Resonance Imaging and Computational Fluid Dynamics ANNALS OF BIOMEDICAL ENGINEERING Suh, G., Les, A. S., Tenforde, A. S., Shadden, S. C., Spilker, R. L., Yeung, J. J., Cheng, C. P., Herfkens, R. J., Dalman, R. L., Taylor, C. A. 2011; 39 (2): 864-883

  Abstract

  Hemodynamic conditions are hypothesized to affect the initiation, growth, and rupture of abdominal aortic aneurysms (AAAs), a vascular disease characterized by progressive wall degradation and enlargement of the abdominal aorta. This study aims to use magnetic resonance imaging (MRI) and computational fluid dynamics (CFD) to quantify flow stagnation and recirculation in eight AAAs by computing particle residence time (PRT). Specifically, we used gadolinium-enhanced MR angiography to obtain images of the vessel lumens, which were used to generate subject-specific models. We also used phase-contrast MRI to measure blood flow at supraceliac and infrarenal locations to prescribe physiologic boundary conditions. CFD was used to simulate pulsatile flow, and PRT, particle residence index, and particle half-life of PRT in the aneurysms were computed. We observed significant regional differences of PRT in the aneurysms with localized patterns that differed depending on aneurysm geometry and infrarenal flow. A bulbous aneurysm with the lowest mean infrarenal flow demonstrated the slowest particle clearance. In addition, improvements in particle clearance were observed with increase of mean infrarenal flow. We postulate that augmentation of mean infrarenal flow during exercise may reduce chronic flow stasis that may influence mural thrombus burden, degradation of the vessel wall, and aneurysm growth.

  View details for DOI 10.1007/s10439-010-0202-4

  View details for Web of Science ID 000287213300022

  View details for PubMedID 21103933

  View details for PubMedCentralID PMC3066149

• Assessment of Elastase-Induced Murine Abdominal Aortic Aneurysms: Comparison of Ultrasound Imaging with In Situ Video Microscopy JOURNAL OF BIOMEDICINE AND BIOTECHNOLOGY Azuma, J., Maegdefessel, L., Kitagawa, T., Dalman, R. L., McConnell, M. V., Tsao, P. S. 2011

  Abstract

  The aim of this study was to definitively assess the validity of noninvasive high-frequency ultrasound (US) measurements of aortic luminal diameter (ALD) in a murine model of elastase-induced abdominal aortic aneurysm in comparison with in situ video microscopy (VM).C57BL/6 mice underwent transient perfusion of the aorta with either elastase (n = 20: Elastase group) or saline (n = 10: Sham). Unoperated mice (n = 10) were also studied.ALD measurements by US had excellent linear correlation and absolute agreement with that by VM in both Control (unoperated or sham-operated mice) and elastase groups (r = 0.96, intraclass correlation coefficient (ICC) = 0.88 and r = 0.93, ICC = 0.92, resp.). Bland-Altman analysis of US compared with VM measurements in both groups indicated good agreement, however US measurements were slightly but significantly higher than VM measurements in the control group (mean bias 0.039 mm, P < .05). Linear regression analysis revealed excellent correlation between US and VM measurements in both groups. (R² = 0.91 in Control group, R² = 0.85 in elastase group.) The reliability of US measurements was also confirmed by ex vivo histological measurements.High-frequency US provides reliable ALD measurements in developing murine abdominal aortic aneurysms.

  View details for DOI 10.1155/2011/252141

  View details for Web of Science ID 000289091200001

  View details for PubMedID 21331328

• METABOLIC SYNDROME AND RISK OF OBSTRUCTIVE SLEEP APNEA (OSA) IN THE ELDERLY 25th Anniversary Meeting of the Associated-Professional-Sleep-Societies (APSS) Mabry, J. E., Herbert, W. G., Myers, J., Dalman, R. L., Powell, A. AMER ACAD SLEEP MEDICINE. 2011: A305–A306

  View details for Web of Science ID 000299834401142

• Nicotine Accelerates the Expansion of Abdominal Aortic Aneurysms in Mice; A Potential Role for miR-21 and miR-26a Maegdefessel, L., Azuma, J., Spin, J. M., Deng, A., McConnell, M. V., Dalman, R. L., Tsao, P. S. LIPPINCOTT WILLIAMS & WILKINS. 2010

  View details for Web of Science ID 000208231602032

• Effects of Exercise Training in Patients With Abdominal Aortic Aneurysm PRELIMINARY RESULTS FROM A RANDOMIZED TRIAL JOURNAL OF CARDIOPULMONARY REHABILITATION AND PREVENTION Myers, J. N., White, J. J., Narasimhan, B., Dalman, R. L. 2010; 30 (6): 374-383

  Abstract

  No effective medical therapy exists for early abdominal aortic aneurysm (AAA) disease. Lower extremity exercise improves aortic hemodynamics and reduces inflammation, but the safety and efficacy of exercise training in AAA disease is unknown. As an interim analysis of our prospective, randomized, longitudinal trial of exercise for AAA suppression, we investigated whether subjects with early disease could safely achieve target metabolic and hemodynamic goals.One hundred eight participants were randomized to exercise training (EX) or usual care (UC). EX subjects participated in a combination of in-house and home exercise training, with efforts directed toward moderate daily exercise participation. Comparisons were made between EX and UC subjects who completed 1 year of follow-up (n = 26 and 31, respectively, mean age 72 ± 8 years). EX and UC groups were compared for safety, cardiopulmonary exercise test responses, weekly energy expenditure, and biometric indices.No paradoxical increase in AAA growth rate or adverse clinical events occurred as a consequence of exercise training. EX participants expended an average of 2269 ± 1207 kcal/wk and increased exercise capacity (42% increase in treadmill time, 24% increase in estimated metabolic equivalents, P = .01 and .08 between groups, respectively). EX participants demonstrated a significant reduction in C-reactive protein and tended to reduce waist circumference and waist-to-hip ratio (P = .06 and .07, respectively).Preliminary analyses suggest that exercise training is well tolerated and sustainable in small AAA subjects over 1 year. Despite age and comorbidities, exercising AAA subjects achieve meaningful exercise targets and significantly modify activity-dependent variables.

  View details for DOI 10.1097/HCR.0b013e3181ebf2db

  View details for Web of Science ID 000284060500003

  View details for PubMedID 20724934

• In Vivo Quantification of Murine Aortic Cyclic Strain, Motion, and Curvature: Implications for Abdominal Aortic Aneurysm Growth JOURNAL OF MAGNETIC RESONANCE IMAGING Goergen, C. J., Barr, K. N., Huynh, D. T., Eastham-Anderson, J. R., Choi, G., Hedehus, M., Dalman, R. L., Connolly, A. J., Taylor, C. A., Tsao, P. S., Greve, J. M. 2010; 32 (4): 847-858

  Abstract

  To develop methods to quantify cyclic strain, motion, and curvature of the murine abdominal aorta in vivo.C57BL/6J and apoE(-/-) mice underwent three-dimensional (3D) time-of-flight MR angiography to position cardiac-gated 2D slices at four locations along the abdominal aorta where circumferential cyclic strain and lumen centroid motion were calculated. From the 3D data, a centerline through the aorta was created to quantify geometric curvature at 0.1-mm intervals. Medial elastin content was quantified with histology postmortem. The location and shape of abdominal aortic aneurysms (AAAs), created from angiotensin II infusion, were evaluated qualitatively.Strain waveforms were similar at all locations and between groups. Centroid motion was significantly larger and more leftward above the renal vessels than below (P < 0.05). Maximum geometric curvature occurred slightly proximal to the right renal artery. Elastin content was similar around the circumference of the vessel. AAAs developed in the same location as the maximum curvature and grew in the same direction as vessel curvature and motion.The methods presented provide temporally and spatially resolved data quantifying murine aortic motion and curvature in vivo. This noninvasive methodology will allow serial quantification of how these parameters influence the location and direction of AAA growth.

  View details for DOI 10.1002/jmri.22331

  View details for Web of Science ID 000282764800010

  View details for PubMedID 20882615

  View details for PubMedCentralID PMC2975391

• Hyperglycemia limits experimental aortic aneurysm progression JOURNAL OF VASCULAR SURGERY Miyama, N., Dua, M. M., Yeung, J. J., Schultz, G. M., Asagami, T., Sho, E., Sho, M., Dalman, R. L. 2010; 52 (4): 975-983

  Abstract

  Diabetes mellitus (DM) is associated with reduced progression of abdominal aortic aneurysm (AAA) disease. Mechanisms responsible for this negative association remain unknown. We created AAAs in hyperglycemic mice to examine the influence of serum glucose concentration on experimental aneurysm progression.Aortic aneurysms were induced in hyperglycemic (DM) and normoglycemic models by using intra-aortic porcine pancreatic elastase (PPE) infusion in C57BL/6 mice or by systemic infusion of angiotensin II (ANG) in apolipoprotein E-deficient (ApoE(-/-)) mice, respectively. In an additional DM cohort, insulin therapy was initiated after aneurysm induction. Aneurysmal aortic enlargement progression was monitored with serial transabdominal ultrasound measurements. At sacrifice, AAA cellularity and proteolytic activity were evaluated by immunohistochemistry and substrate zymography, respectively. Influences of serum glucose levels on macrophage migration were examined in separate models of thioglycollate-induced murine peritonitis.At 14 days after PPE infusion, AAA enlargement in hyperglycemic mice (serum glucose ≥ 300 mg/dL) was less than that in euglycemic mice (PPE-DM: 54% ± 19% vs PPE: 84% ± 24%, P < .0001). PPE-DM mice also demonstrated reduced aortic mural macrophage infiltration (145 ± 87 vs 253 ± 119 cells/cross-sectional area, P = .0325), elastolysis (% residual elastin: 20% ± 7% vs 12% ± 6%, P = .0209), and neovascularization (12 ± 8 vs 20 ± 6 vessels/high powered field, P = .0229) compared with PPE mice. Hyperglycemia limited AAA enlargement after ANG infusion in ApoE(-/-) mice (ANG-DM: 38% ± 12% vs ANG: 61% ± 37% at day 28). Peritoneal macrophage production was reduced in response to thioglycollate stimulation in hyperglycemic mice, with limited augmentation noted in response to vascular endothelial growth factor administration. Insulin therapy reduced serum glucose levels and was associated with AAA enlargement rates intermediate between euglycemic and hyperglycemic mice (PPE: 1.21 ± 0.14 mm vs PPE-DM: 1.00 ± 0.04 mm vs PPE-DM + insulin: 1.14 ± 0.05 mm).Hyperglycemia reduces progression of experimental AAA disease; lowering of serum glucose levels with insulin treatment diminishes this protective effect. Identifying mechanisms of hyperglycemic aneurysm inhibition may accelerate development of novel clinical therapies for AAA disease.

  View details for DOI 10.1016/j.jvs.2010.05.086

  View details for Web of Science ID 000282660300023

  View details for PubMedID 20678880

  View details for PubMedCentralID PMC2987703

• Hyperglycemia modulates plasminogen activator inhibitor-1 expression and aortic diameter in experimental aortic aneurysm disease SURGERY Dua, M. M., Miyama, N., Azuma, J., Schultz, G. M., Sho, M., Morser, J., Dalman, R. L. 2010; 148 (2): 429-435

  Abstract

  Extracellular matrix degradation is a sentinel pathologic feature of abdominal aortic aneurysm (AAA) disease. Diabetes mellitus, a negative risk factor for AAA, may impair aneurysm progression through its influence on the fibrinolytic system. We hypothesize that hyperglycemia limits AAA progression through effects on endogenous plasminogen activator inhibitor-1 (PAI-1) levels and subsequent reductions in plasmin generation.Experimental AAAs were induced in diabetic and control mice via the intra-aortic elastase infusion method. Serial transabdominal high-frequency ultrasound examinations were performed to monitor aortic diameter following elastase infusion. Circulating PAI-1 and plasmin alpha2-antiplasmin (PAP) complex concentrations were determined by ELISA and local expression of PAI-1 levels was examined by RT-PCR and immunohistochemistry.Hyperglycemia was associated with reduced AAA diameter, increased plasma PAI-1 concentration and reduced plasmin generation. Aneurysmal aortic PAI-1 gene expression increased in parallel with plasma concentration, with peak expression occurring early after aneurysm initiation.Hyperglycemia increases PAI-1 expression and attenuates AAA diameter in experimental AAA disease. These results emphasize the role of the fibrinolytic pathway in AAA pathophysiology, and suggest a candidate mechanism for hyperglycemic inhibition of AAA disease.

  View details for DOI 10.1016/j.surg.2010.05.014

  View details for Web of Science ID 000280433200034

  View details for PubMedID 20561659

  View details for PubMedCentralID PMC2905480

• Spatial Distribution of Microemboli Following Carotid Interventions 25th Annual Meeting of the Western-Vascular-Society Zhou, W., Laird, A. R., Eickhoff, S. B., Fox, M., Chan, G., Lane, B., Dalman, R., Rosen, A. MOSBY-ELSEVIER. 2010: 523–24

  View details for Web of Science ID 000280455900050

• Enhanced Abdominal Aortic Aneurysm Formation in Thrombin-Activatable Procarboxypeptidase B-Deficient Mice ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY Schultz, G., Tedesco, M. M., Sho, E., Nishimura, T., Sharif, S., Du, X., Myles, T., Morser, J., Dalman, R. L., Leung, L. L. 2010; 30 (7): 1363-1370

  Abstract

  To determine whether procarboxypeptidase B (pCPB)(-/-) mice are susceptible to accelerated abdominal aortic aneurysm (AAA) development secondary to unregulated OPN-mediated mural inflammation in the absence of CPB inhibition.Thrombin/thrombomodulin cleaves thrombin-activatable pCPB or thrombin-activatable fibrinolysis inhibitor, activating CPB, which inhibits the generation of plasmin and inactivates proinflammatory mediators (complement C5a and thrombin-cleaved osteopontin [OPN]). Apolipoprotein E(-/-)OPN(-/-) mice are protected from experimental AAA formation. Murine AAAs were created via intra-aortic porcine pancreatic elastase (PPE) infusion. Increased mortality secondary to AAA rupture was observed in pCPB(-/-) mice at the standard PPE dose. At reduced doses of PPE, pCPB(-/-) mice developed larger AAAs than wild-type controls (1.01+/-0.27 versus 0.68+/-0.05 mm; P=0.02 [mean+/-SD]). C5(-/-) and OPN(-/-) mice were not protected against AAA development. Treatment with tranexamic acid inhibited plasmin generation and abrogated enhanced AAA progression in pCPB(-/-) mice.This study establishes the role of CPB in experimental AAA disease, indicating that CPB has a broad anti-inflammatory role in vivo. Enhanced AAA formation in the PPE model is the result of increased plasmin generation, not unregulated C5a- or OPN-mediated mural inflammation.

  View details for DOI 10.1161/ATVBAHA.109.202259

  View details for Web of Science ID 000278856600013

  View details for PubMedID 20431069

• Hemodynamic Influences on abdominal aortic aneurysm disease: Application of biomechanics to aneurysm pathophysiology VASCULAR PHARMACOLOGY Dua, M. M., Dalman, R. L. 2010; 53 (1-2): 11-21

  Abstract

  "Atherosclerotic" abdominal aortic aneurysms (AAAs) occur with the greatest frequency in the distal aorta. The unique hemodynamic environment of this area predisposes it to site-specific degenerative changes. In this review, we summarize the differential hemodynamic influences present along the length of the abdominal aorta, and demonstrate how alterations in aortic flow and wall shear stress modify AAA progression in experimental models. Improved understanding of aortic hemodynamic risk profiles provides an opportunity to modify patient activity patterns to minimize the risk of aneurysmal degeneration.

  View details for DOI 10.1016/j.vph.2010.03.004

  View details for Web of Science ID 000278450300002

  View details for PubMedID 20347049

  View details for PubMedCentralID PMC2880166

• Combined endovascular and open operative approach for mycotic carotid aneurysm JOURNAL OF VASCULAR SURGERY Tsai, T. C., Barot, N., Dalman, R., Mihm, F. 2010; 51 (6): 1514-1516

  Abstract

  Mycotic aneurysms of the extracranial carotid artery are rare and warrant surgical intervention. Management involves open and endovascular approaches. We report the case of a 67-year-old woman with an Escherichia coli soft-tissue infection of the right retropharyngeal space and subsequent mycotic carotid aneurysm and thrombosis of the internal jugular vein. The patient presented with a pulsatile mass and right middle cerebral artery stroke. Our surgical management involved coil embolization of the aneurysm to provide for vascular control, with resection of the common carotid artery, internal carotid artery, and extracranial carotid artery branches, along with the internal jugular vein.

  View details for DOI 10.1016/j.jvs.2009.12.067

  View details for Web of Science ID 000277974200026

  View details for PubMedID 20304585

• Cardiopulmonary Exercise Testing In Abdominal Aortic Aneurysm: Profile, Safety, And Mortality Estimates 57th Annual Meeting of the American-College-of-Sports-Medicine / Inaugural World Congress on Exercise is Medicine Myers, J. N., Powell, A., Smith, K., Dalman, R. LIPPINCOTT WILLIAMS & WILKINS. 2010: 725–25

  View details for Web of Science ID 000290226302520

• Quantification of Hemodynamics in Abdominal Aortic Aneurysms During Rest and Exercise Using Magnetic Resonance Imaging and Computational Fluid Dynamics ANNALS OF BIOMEDICAL ENGINEERING Les, A. S., Shadden, S. C., Figueroa, C. A., Park, J. M., Tedesco, M. M., Herfkens, R. J., Dalman, R. L., Taylor, C. A. 2010; 38 (4): 1288-1313

  Abstract

  Abdominal aortic aneurysms (AAAs) affect 5-7% of older Americans. We hypothesize that exercise may slow AAA growth by decreasing inflammatory burden, peripheral resistance, and adverse hemodynamic conditions such as low, oscillatory shear stress. In this study, we use magnetic resonance imaging and computational fluid dynamics to describe hemodynamics in eight AAAs during rest and exercise using patient-specific geometric models, flow waveforms, and pressures as well as appropriately resolved finite-element meshes. We report mean wall shear stress (MWSS) and oscillatory shear index (OSI) at four aortic locations (supraceliac, infrarenal, mid-aneurysm, and suprabifurcation) and turbulent kinetic energy over the entire computational domain on meshes containing more than an order of magnitude more elements than previously reported results (mean: 9.0-million elements; SD: 2.3 M; range: 5.7-12.0 M). MWSS was lowest in the aneurysm during rest 2.5 dyn/cm(2) (SD: 2.1; range: 0.9-6.5), and MWSS increased and OSI decreased at all four locations during exercise. Mild turbulence existed at rest, while moderate aneurysmal turbulence was present during exercise. During both rest and exercise, aortic turbulence was virtually zero superior to the AAA for seven out of eight patients. We postulate that the increased MWSS, decreased OSI, and moderate turbulence present during exercise may attenuate AAA growth.

  View details for DOI 10.1007/s10439-010-9949-x

  View details for Web of Science ID 000276046600003

  View details for PubMedID 20143263

• Supraceliac and Infrarenal Aortic Flow in Patients with Abdominal Aortic Aneurysms: Mean Flows, Waveforms, and Allometric Scaling Relationships. Cardiovascular engineering and technology Les, A. S., Yeung, J. J., Schultz, G. M., Herfkens, R. J., Dalman, R. L., Taylor, C. A. 2010; 1 (1)

  Abstract

  Hemodynamic forces are thought to play a critical role in abdominal aortic aneurysm (AAA) growth. In silico and in vitro simulations can be used to study these forces, but require accurate aortic geometries and boundary conditions. Many AAA simulations use patient-specific geometries, but utilize inlet boundary conditions taken from a single, unrelated, healthy young adult.In this study, we imaged 43 AAA patients using a 1.5 T MR scanner. A 24-frame cardiac-gated one-component phase-contrast magnetic resonance imaging sequence was used to measure volumetric flow at the supraceliac (SC) and infrarenal (IR) aorta, where flow information is typically needed for simulation. For the first 36 patients, individual waveforms were interpolated to a 12-mode Fourier curve, peak-aligned, and averaged. Allometric scaling equations were derived from log-log plots of mean SC and IR flow vs. body mass, height, body surface area (BSA), and fat-free body mass. The data from the last seven patients were used to validate our model.Both the SC and IR averaged waveforms had the biphasic shapes characteristic of older adults, and mean SC and IR flows over the cardiac cycle were 51.2 ± 10.3 and 17.5 ± 5.44 mL/s, respectively. Linear regression of the log-log plots revealed that BSA was most strongly predictive of mean SC (R(2) = 0.29) and IR flow (R(2) = 0.19), with the highest combined R(2). When averaged, the measured and predicted waveforms for the last seven patients agreed well.We present a method to estimate SC and IR mean flows and waveforms for AAA simulation.

  View details for DOI 10.1007/s13239-010-0004-8

  View details for PubMedID 24324530

• A survey of demographics, motivations, and backgrounds among applicants to the integrated 0+5 vascular surgery residency JOURNAL OF VASCULAR SURGERY Lee, J. T., Teshome, M., De Virgilio, C., Ishaque, B., Qiu, M., Dalman, R. L. 2010; 51 (2): 496-503

  Abstract

  The 0 + 5 integrated vascular surgery (VS) residency has altered the training paradigm for future vascular specialists. Rising interest in these novel programs highlights our need to better understand the applicant pool. We compared demographics and surveyed recent applicants to our integrated program to gain more insight into their background and motivation for accelerated vascular training.Demographics and objective parameters were determined from all 65 applicants to the integrated VS program at Stanford University Medical Center and compared to 58 applicants interviewed by the general surgery (GS) program at Harbor-UCLA Medical Center by querying the Electronic Residency Application System for the programs in 2009. There was no overlap of applicants between programs. An anonymous, voluntary Web-based survey was sent to these cohorts with a response rate of 82% for VS applicants and 60% for GS applicants. Subjects were queried regarding their background, personal experience, prior exposure to VS, and motivations for residency specialty selection.Applicants to integrated VS programs tended to be older, were less likely to be from a US medical school, had a higher number of publications, and a higher percentage of cardiovascular-related publications than the GS applicants. When stratified by the 27 VS applicants (41%) that were offered an interview, this highly selected and desirable group for training was nearly 40% female, more likely to have an additional degree (PhD, master's), just as likely to be in the top quartile of their medical school class (60%), and score equally well on standardized board examinations (90th percentile) than the top GS applicants offered interviews. Survey data revealed that the majority of career choices (65%) were made during the third and fourth years of medical school. Factors most strongly influencing the decision to choose VS as a career were endovascular technologies/devices, challenging open vascular operations, clinical rotations on vascular surgery, the aging patient population, and perceived need for vascular surgeons and vascular surgeon mentorship. The most common reasons cited for particularly pursuing an integrated 0 + 5 VS training program were (1) more focused training/integration of cardiovascular medicine, (2) interest in catheter-based endovascular therapies, and (3) shorter time in training. Of the GS applicants, 58% indicated they would be interested in applying to an integrated residency in their subspecialty of interest, and 45% listed vascular surgery as a potential fellowship option after general surgery.Applicants to 0 + 5 integrated vascular residencies were more likely to have rotated on a vascular surgery service, observed vascular cases, identified a vascular surgery mentor, and been actively involved in cardiovascular research. The quality of the top VS applicant based on class rank and test scores is comparable to the top GS applicants, yet the VS applicant has a higher percentage of advanced degrees, more publications, and more involvement in cardiovascular research. Institutional strategies to increase medical student exposure to vascular surgery clinically and via research programs will optimize our ability to attract and train the best candidates in these new training programs.

  View details for DOI 10.1016/j.jvs.2009.08.076

  View details for Web of Science ID 000274602800033

  View details for PubMedID 20022205

• Quantifying In Vivo Hemodynamic Response to Exercise in Patients With Intermittent Claudication and Abdominal Aortic Aneurysms Using Cine Phase-Contrast MRI JOURNAL OF MAGNETIC RESONANCE IMAGING Tenforde, A. S., Cheng, C. P., Suh, G., Herfkens, R. J., Dalman, R. L., Taylor, C. A. 2010; 31 (2): 425-429

  Abstract

  To evaluate rest and exercise hemodynamics in patients with abdominal aortic aneurysms (AAA) and peripheral occlusive disease (claudicants) using phase-contrast MRI.Blood velocities were acquired by means of cardiac-gated cine phase-contrast in a 0.5 Tesla (T) open MRI. Volumetric flow was calculated at the supraceliac (SC), infrarenal (IR), and mid-aneurysm (MA) levels during rest and upright cycling exercise using an MR-compatible exercise cycle.Mean blood flow increased during exercise (AAA: 130%, Claudicants: 136% of resting heart rate) at the SC and IR levels for AAA participants (2.6 +/- 0.6 versus 5.8 +/- 1.6 L/min, P < 0.001 and 0.8 +/- 0.4 versus 5.1 +/- 1.7 L/min, P < 0.001) and claudicants (2.3 +/- 0.5 versus 4.5 +/- 0.9 L/min, P < 0.005 and 0.8 +/- 0.2 versus 3.3 +/- 0.9 L/min, P < 0.005). AAA participants had a significant decrease in renal and digestive blood flow from rest to exercise (1.8 +/- 0.7 to 0.7 +/- 0.6 L/min, P < 0.01). The decrease in renal and digestive blood flow during exercise correlated with daily activity level for claudicants (R = 0.81).Abdominal aortic hemodynamic changes due to lower extremity exercise can be quantified in patients with AAA and claudication using PC-MRI. The redistribution of blood flow during exercise was significant and different between the two disease states.

  View details for DOI 10.1002/jmri.22055

  View details for Web of Science ID 000274117200019

  View details for PubMedID 20099356

  View details for PubMedCentralID PMC2963312

• ASSOCIATION OF PHYSICAL ACTIVITY & RISK OF OBSTRUCTIVE SLEEP APNEA (OSA) IN THE ELDERLY Mabry, J. E., Sridhara, R., Herbert, W. G., Myers, J., Dalman, R. L. AMER ACAD SLEEP MEDICINE. 2010: A131–A132

  View details for Web of Science ID 000208208000379

• In vivo Targeted Molecular Imaging of Matrix Metalloproteinase Inhibition in Experimental Abdominal Aortic Aneurysm Disease 82nd National Conference and Exhibitions and Scientific Sessions of the American-Heart-Association Dua, M. M., Schultz, G. M., Miyama, N., Peterson, J. D., Dalman, R. L. LIPPINCOTT WILLIAMS & WILKINS. 2009: S358–S359

  View details for Web of Science ID 000271831500236

• The utility of endovascular simulation to improve technical performance and stimulate continued interest of preclinical medical students in vascular surgery. Journal of surgical education Lee, J. T., Qiu, M., Teshome, M., Raghavan, S. S., Tedesco, M. M., Dalman, R. L. 2009; 66 (6): 367-373

  Abstract

  New training paradigms in vascular surgery allow for early specialization out of medical school. Surgical simulation has emerged as an educational tool for trainees to practice procedures in a controlled environment allowing interested medical students to perform procedures without compromising patient safety. The purpose of this study is to assess the ability of a simulation-based curriculum to improve the technical performance and interest level of medical students in vascular surgery.Prospective observational cohort study of medical student performance.Academic medical center.Forty-one medical students (23 first year, 15 second year, 3 other) enrolled in a vascular surgery elective course. Students completed a survey of their interests and performed a renal stent procedure on an endovascular simulator (pretest). The curriculum consisted of didactic teaching and weekly mentored simulator sessions and concluded with a final renal stent procedure on the simulator (posttest). Objective procedural measures were determined during the pre- and posttest by the simulator, and subjective performance was graded by expert observers utilizing a structured global assessment scale. After the course, the students were surveyed as to their opinions about vascular surgery as a career option. Finally, 1 year after the course, all students were again surveyed to determine continued interest in vascular surgery.The objective and subjective criteria measured on the simulator and structured global assessment scale significantly improved from pre- to posttest in terms of performer technical skill, patient safety measures, and structured global assessments. Before beginning the course, 8.5% of the students expressed high interest in vascular surgery, and after completing the course 70% were seriously considering vascular surgery as a career option (p = 0.0001). More than 95% of the students responded that endovascular simulation increased their knowledge and interest in vascular surgery. In the 1-year follow-up survey (n = 23 medical students), 35% had already entered their clinical years. Seventy percent of the students were still considering vascular surgery, while several other career options were still popular including the surgical subspecialties (70%), interventional cardiology (57%), and interventional radiology (48%). Most respondents indicated the major reasons for continued interest in vascular surgery were the ability to practice endovascular procedures on the simulator (100%) and mentorship from vascular surgery faculty (78%).The use of high fidelity endovascular simulation within an introductory vascular surgery course improves medical student performance with respect to technical skill, patient safety parameters, and global performance assessment. Mentored exposure to endovascular procedures on the simulator positively impacts long term medical student attitudes towards vascular surgery. Simulator-based courses may have the potential to be an important component in the assessment and recruitment of medical students for future surgical training programs.

  View details for DOI 10.1016/j.jsurg.2009.06.002

  View details for PubMedID 20142137

• Analysis of In Situ and Ex Vivo Vascular Endothelial Growth Factor Receptor Expression During Experimental Aortic Aneurysm Progression ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY Tedesco, M. M., Terashima, M., Blankenberg, F. G., Levashova, Z., Spin, J. M., Backer, M. V., Backer, J. M., Sho, M., Sho, E., McConnell, M. V., Dalman, R. L. 2009; 29 (10): 1452-?

  Abstract

  Mural inflammation and neovascularization are characteristic pathological features of abdominal aortic aneurysm (AAA) disease. Vascular endothelial growth factor receptor (VEGFR) expression may also mediate AAA growth and rupture. We examined VEGFR expression as a function of AAA disease progression in the Apolipoprotein E-deficient (Apo E(-/-)) murine AAA model.Apo E(-/-) mice maintained on a high-fat diet underwent continuous infusion with angiotensin II at 1000 ng/kg/min (Ang II) or vehicle (Control) via subcutaneous osmotic pump. Serial transabdominal ultrasound measurements of abdominal aortic diameter were recorded (n=16 mice, 3 to 4 time points per mouse) for up to 28 days. Near-infrared receptor fluorescent (NIRF) imaging was performed on Ang II mice (n=9) and Controls (n=5) with scVEGF/Cy, a single-chain VEGF homo-dimer labeled with Cy 5.5 fluorescent tracer (7 to 18 microg/mouse IV). NIRF with inactivated single chain VEGF/Cy tracer (scVEGF/In, 18 microg/mouse IV) was performed on 2 additional Ang II mice to control for nonreceptor-mediated tracer binding and uptake. After image acquisition and sacrifice, aortae were harvested for analysis. An additional AAA mouse cohort received either an oral angiogenesis inhibitor or suitable negative or positive controls to clarify the significance of angiogenesis in experimental aneurysm progression. Aneurysms developed in the suprarenal aortic segment of all Ang II mice. Significantly greater fluorescent signal was obtained from aneurysmal aorta as compared to remote, uninvolved aortic segments in Ang II scVEGF/Cy mice or AAA in scVEGF/In mice or suprarenal aortic segments in Control mice. Signal intensity increased in a diameter-dependent fashion in aneurysmal segments. Immunostaining confirmed mural VEGFR-2 expression in medial smooth muscle cells. Treatment with an angiogenesis inhibitor attenuated AAA formation while decreasing mural macrophage infiltration and CD-31(+) cell density.Mural VEGFR expression, as determined by scVEGF/Cy fluorescent imaging and VEGFR-2 immunostaining, increases in experimental AAAs in a diameter-dependent fashion. Angiogenesis inhibition limits AAA progression. Clinical VEGFR expression imaging strategies, if feasible, may improve real-time monitoring of AAA disease progression and response to suppressive strategies.

  View details for DOI 10.1161/ATVBAHA.109.187757

  View details for Web of Science ID 000269848600010

  View details for PubMedID 19574559

  View details for PubMedCentralID PMC2752726

• SVS practice guidelines for the care of patients with an abdominal aortic aneurysm: Executive summary JOURNAL OF VASCULAR SURGERY Chaikof, E. L., Brewster, D. C., Dalman, R. L., Makaroun, M. S., Illig, K. A., Sicard, G. A., Timaran, C. H., Upchurch, G. R., Veith, F. J. 2009; 50 (4): 880-896

  View details for DOI 10.1016/j.jvs.2009.07.001

  View details for Web of Science ID 000270404500024

  View details for PubMedID 19786241

• The care of patients with an abdominal aortic aneurysm: the Society for Vascular Surgery practice guidelines. Journal of vascular surgery Chaikof, E. L., Brewster, D. C., Dalman, R. L., Makaroun, M. S., Illig, K. A., Sicard, G. A., Timaran, C. H., Upchurch, G. R., Veith, F. J. 2009; 50 (4): S2-49

  View details for DOI 10.1016/j.jvs.2009.07.002

  View details for PubMedID 19786250

• The care of patients with an abdominal aortic aneurysm: The Society for Vascular Surgery practice guidelines JOURNAL OF VASCULAR SURGERY Chaikof, E. L., Brewster, D. C., Dalman, R. L., Makaroun, M. S., Illig, K. A., Sicard, G. A., Timaran, C. H., Upchurch, G. R., Veith, F. J. 2009; 50: 2S-49S

  View details for DOI 10.1016/j.jvs.2009.07.002

  View details for Web of Science ID 000270404600002

• Preoperative Thrombus Volume Predicts Sac Regression After Endovascular Aneurysm Repair JOURNAL OF ENDOVASCULAR THERAPY Yeung, J. J., Hernandez-Boussard, T. M., Song, T. K., Dalman, R. L., Lee, J. T. 2009; 16 (3): 380-388

  Abstract

  To examine whether preoperative aneurysm thrombus volume correlated with abdominal aortic aneurysm (AAA) sac regression following endovascular aneurysm repair (EVAR).Clinical records and computed tomographic angiograms (CTAs) from patients undergoing EVAR from 2003 to 2008 were reviewed. Inclusion criteria for this study were available preoperative CTA images, >or=12-month follow-up with surveillance imaging, lack of re-intervention at 12 months, and treatment with commercially available devices. Patients with ruptured AAAs, those requiring an aortomonoiliac stent-graft, and clinical trial cases were excluded. Based on these criteria, satisfactory images and clinical follow-up were available in 100 patients (90 men; mean age 76.8 years, range 55-95). Preoperative CTAs were categorized as demonstrating "minimal," "moderate," or "severe" aneurysm thrombus load by 2 independent examiners blinded to clinical outcome. Percentage of the aortic cross-sectional area occluded by clot (% clot area) was calculated as [(total area) - (luminal area)]/(total area). Multivariate logistic regression analysis was performed to determine predictors of sac shrinkage at long-term follow-up.AAA thrombus was classified as minimal in 24%, moderate in 23%, and severe in 53%. Thrombus area averaged 11%+/-13%, 41%+/-14%, and 72+/-12% in each group, respectively. By multivariate analysis, minimal thrombus (OR = 1.47) and greater AAA diameter (OR = 1.3) were independent predictors of sac regression at 1, 6, and 12 months (all p<0.05). Presence of neck plaque and endoleak were also independent predictors of sac expansion (p<0.05). Patients with severe preoperative thrombus were less likely to demonstrate sac regression even in the absence of endoleak. Thrombus judgment (subjective) and percent clot area (objective) were strongly correlated (R = 0.82, p<0.05). Interobserver agreement on thrombus judgment was 86%.Thrombus burden on preoperative CTA is a strong independent predictor of sac regression following EVAR. If validated by prospective studies, relative thrombus burden should be incorporated into postoperative surveillance algorithms to define procedural success and optimize the timing and cost-effectiveness of cross-sectional imaging.

  View details for Web of Science ID 000268117500019

  View details for PubMedID 19642793

• Apelin prevents aortic aneurysm formation by inhibiting macrophage inflammation AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY Leeper, N. J., Tedesco, M. M., Kojima, Y., Schultz, G. M., Kundu, R. K., Ashley, E. A., Tsao, P. S., Dalman, R. L., Quertermous, T. 2009; 296 (5): H1329-H1335

  Abstract

  Apelin is a potent inodilator with recently described antiatherogenic properties. We hypothesized that apelin might also attenuate abdominal aortic aneurysm (AAA) formation by limiting disease-related vascular wall inflammation. C57BL/6 mice implanted with osmotic pumps filled with apelin or saline were treated with pancreatic elastase to create infrarenal AAAs. Mice were euthanized for aortic PCR analysis or followed ultrasonographically and then euthanized for histological analysis. The cellular expression of inflammatory cytokines and chemokines in response to apelin was also assessed in cultured macrophages, smooth muscle cells, and fibroblasts. Apelin treatment resulted in diminished AAA formation, with a 47% reduction in maximal cross-sectional area (0.74 vs. 1.39 mm(2), P < 0.03) and a 57% reduction in macrophage infiltrate (113 vs. 261.3 cells/high-power field, P < 0.0001) relative to the saline-treated group. Apelin infusion was also associated with significantly reduced aortic macrophage colony-stimulating factor expression and decreased monocyte chemattractant protein (MCP)-1, macrophage inflammatory protein (MIP)-1alpha, interleukin (IL)-6, and tumor necrosis factor (TNF)-alpha mean mRNA levels. Apelin stimulation of cultured macrophages significantly reduced MCP-1 and TNF-alpha mRNA levels relative to baseline (2.03- and 1.89-fold reduction, P < 0.03, respectively) but did not affect intimal adhesion molecule expression or medial or adventitial cell cytokine production. Apelin significantly reduces aneurysm formation in the elastase model of human AAA disease. The mechanism appears to be decreased macrophage burden, perhaps related to an apelin-mediated decrease in proinflammatory cytokine and chemokine activation.

  View details for DOI 10.1152/ajpheart.01341.2008

  View details for Web of Science ID 000265659100020

  View details for PubMedID 19304942

• Not All "Microemboli" are Created Equal: Hypotension During Carotid Stenting May be a Cause for Some Lesions. American-Association-International-Stroke Conference 2009 Kleinman, J. T., Tedesco, M. M., Gottesman, R. F., Lane, B., Zhou, W., Dalman, R. L., Lee, J. T. LIPPINCOTT WILLIAMS & WILKINS. 2009: E175–E175

  View details for Web of Science ID 000264709500373

• Developments in Non-Surgical Therapies for Abdominal Aortic Aneurysm CURRENT VASCULAR PHARMACOLOGY Golledge, J., Dalman, R. L., Norman, P. E. 2009; 7 (2): 153-158

  Abstract

  The introduction of ultrasound screening combined with the increasingly elderly population means that the number of small abdominal aortic aneurysms (AAAs) detected is expected to increase over the next decade. At present open or endovascular surgery are the only treatment options for AAA. In this mini-review we discuss the rationale and on-going attempts to develop non-surgical therapies for AAA.

  View details for Web of Science ID 000263970500005

  View details for PubMedID 19355998

• Reduction of postprocedure microemboli following retrospective quality assessment and practice improvement measures for carotid angioplasty and stenting JOURNAL OF VASCULAR SURGERY Tedesco, M. M., Dalman, R. L., Zhou, W., Coogan, S. M., Lane, B., Lee, J. T. 2009; 49 (3): 607-612

  Abstract

  We have previously demonstrated a 70% incidence of microemboli on diffusion weighted magnetic resonance imaging (DW-MRI) following carotid angioplasty and stenting (CAS). The purpose of this study is to compare the incidence of microemboli in two distinct time periods when procedural modifications were implemented into a CAS program.Following a retrospective quality review of our CAS cohort (n = 27) from November 2004 through April 2006 (period 1), we enrolled patients (n = 20) from May 2006 through February 2008 (period 2) undergoing CAS into a prospective cohort that included obtaining pre- and postprocedure DW-MRI exams. Procedural modifications during period 2 included the preferential use of closed-cell systems (60% vs 0% in period 1), early heparinization at the initiation of arterial access, and elimination of an arch angiogram. The hospital records of these 47 patients were reviewed; symptoms, comorbidities, lesion characteristics, periprocedural information, and postoperative outcomes were collected. The incidence and location of acute, postprocedural microemboli were determined using DW-MRIs.Twenty (74%) CAS patients from period 1 and seven (35%) patients from period 2 demonstrated acute microemboli on postprocedural DW-MRI (P = .02). The mean number of microemboli in period 1 was 4.1 +/- 5.3 vs 1.5 +/- 2.7 during period 2 (P = .04). Two of the 27 patients (7.4%) during period 1 experienced temporary neurologic changes that resolved within 36 hours. None of the patients during period 2 exhibited any neurologic changes. Patient demographics, comorbidities, and presenting symptoms were similar between the two groups except for smoking prevalence, female presence, and obesity (BMI > 30). Period 2 patients when compared with period 1 had more technically challenging anatomy with more calcified lesions (68% vs 27%), longer lesions (15.9 mm vs 8.2 mm), and higher incidence of ulceration (55% vs 27%) (all P < .04).Despite successful performance of 47 consecutive CAS procedures without permanent neurologic sequelae, significant reductions in periprocedural embolic events as identified via DW-MRI lesions may be achieved through implementation of quality improvement measures identified through continuous outcome analysis. The long-term neurologic benefits associated with reduced subclinical neurologic events remains to be determined.

  View details for DOI 10.1016/j.jvs.2008.10.031

  View details for Web of Science ID 000263802000015

  View details for PubMedID 19135833

• Identifying abdominal aortic aneurysm risk factors in postmenopausal women. Women's health (London, England) Dua, M. M., Dalman, R. L. 2009; 5 (1): 33-37

  Abstract

  Evaluation of: Lederle FA, Larson JC, Margolis KL et al.: Abdominal aortic aneurysm events in the Women's Health Initiative: cohort study. Br. Med. J. 337, A1724 (2008). A linked cohort study of 161,808 postmenopausal women aged 50-79 years enrolled in the Women's Health Initiative was conducted during which participants were followed for the incidence of abdominal aortic aneurysm repair or rupture. This study evaluated the association between potential risk factors and subsequent abdominal aortic aneurysm events in women. A total of 467 women reported a diagnosis of abdominal aortic aneurysm before entering the study or during participation, with 184 aneurysm-related events identified. Abdominal aortic aneurysm events were strongly associated with age and smoking and negatively associated with diabetes and baseline use of postmenopausal hormone supplementation. Previous studies investigating abdominal aortic aneurysm have focused primarily on men, with little reliable information available on women. This study contributes a large female cohort to provide better insight into gender-specific abdominal aortic aneurysm risks and disease associations.

  View details for DOI 10.2217/17455057.5.1.33

  View details for PubMedID 19102638

• Creation of murine experimental abdominal aortic aneurysms with elastase. Journal of visualized experiments : JoVE Azuma, J., Asagami, T., Dalman, R., Tsao, P. S. 2009

  Abstract

  Transient intraluminal infusion of porcine pancreatic elastase into the infrarenal segment of the abdominal aorta is the most widely used animal model of abdominal aortic aneurysm (AAA) ever since it was first described in rats by Anidjar and colleagues.(1) The rationale for its development was based on the disrupted nature of elastin observed in AAAs. This rat model has been modified to produce AAAs in the infrarenal aortic region of mice.(2) The model has the ability to add broad insight into the pathobiology of AAA due to the emergence of numerous transgenic and gene knockout mice. Moreover, it is a viable platform to test potential therapeutic agents for AAA. In this video, we demonstrate the elastase infusion AAA procedure used in our laboratory. Mice are anesthetized using 2.5% isoflurane, and a laparotomy is performed under sterile conditions. The abdominal aortais isolated with the assistance of an operating stereomicroscope (Leica). After placing temporary ligatures around the proximal and distal aorta, an aortotomy is created at the bifurcation with the tip of a 30-gauge needle. A heat-tapered segment of PE-10 polyethylene tubing is introduced through the aortotomy and secured. The aortic lumen is subsequently perfused for 5-15 minutes at 100 mm Hg with saline containing type I porcine pancreatic elastase (4.5 U/mL; Sigma Chemical Co.). After removing the perfusion catheter, the aortotomy is repaired without constriction of the lumen.

  View details for DOI 10.3791/1280

  View details for PubMedID 19629030

• HEMODYNAMICS IN ABDOMINAL AORTIC ANEURYSMS AT REST AND GRADED LEVELS OF EXERCISE ASME Summer Bioengineering Conference Suh, G. K., Tenforde, A., Shadden, S., Spilker, R., Cheng, C. P., Herfkens, R. J., Dalman, R. L., Taylor, C. A. AMER SOC MECHANICAL ENGINEERS. 2009: 383–384

  View details for Web of Science ID 000280089000192

• USING COMPUTATIONAL FLUID DYNAMICS TO DESIGN AND OPTIMIZE A NOVEL ENDOVASCULAR PROCEDURE FOR CAROTID STENOSIS REPAIR ASME Summer Bioengineering Conference Yeh, V., Figueroa, C. A., Les, A., Ho, J. P., Dalman, R., Taylor, C. A. AMER SOC MECHANICAL ENGINEERS. 2009: 593–594

  View details for Web of Science ID 000263364700297

• VOLUMETRIC FLOW AT THE SUPRACELIAC AND INFRARENAL LEVELS IN PATIENTS WITH ABDOMINAL AORTIC ANEURYSM: WAVEFORMS AND ALLOMETRIC SCALING RELATIONSHIPS ASME Summer Bioengineering Conference Les, A. S., Yeung, J. J., Young, P. M., Herfkens, R. J., Dalman, R. L., Taylor, C. A. AMER SOC MECHANICAL ENGINEERS. 2009: 921–922

  View details for Web of Science ID 000280089000461

• Relationship Between Hypotension and Distribution of Microemboli on DW-MRI Following Carotid Angioplasty and Stenting 81st Annual Scientific Session of the American-Heart-Association Lee, J. T., Kleinman, J. T., Teshome, M., Raghavan, S., Tedesco, M. M., Lane, B., Zhou, W., Dalman, R. L. LIPPINCOTT WILLIAMS & WILKINS. 2008: S1077–S1077

  View details for Web of Science ID 000262104504278

• Enhanced Abdominal Aortic Aneurysm (AAA) Formation in Procarboxypeptidase B (pCPB)-Deficient Mice 81st Annual Scientific Session of the American-Heart-Association Tedesco, M. M., Sho, E., Nishimura, T., Sharif, S., Du, X., Dalman, R. L., Leung, L. L. LIPPINCOTT WILLIAMS & WILKINS. 2008: S310–S310

  View details for Web of Science ID 000262104500192

• Decreased cancer risk after iron reduction in patients with peripheral arterial disease: Results from a randomized trial JOURNAL OF THE NATIONAL CANCER INSTITUTE Zacharski, L. R., Chow, B. K., Howes, P. S., Shamayeva, G., Baron, J. A., Dalman, R. L., Malenka, D. J., Ozaki, C. K., Lavori, P. W. 2008; 100 (14): 996-1002

  Abstract

  Excess iron has been implicated in cancer risk through increased iron-catalyzed free radical-mediated oxidative stress.A multicenter randomized, controlled, single-blinded clinical trial (VA Cooperative Study #410) tested the hypothesis that reducing iron stores by phlebotomy would influence vascular outcomes in patients with peripheral arterial disease. Patients without a visceral malignancy in the last 5 years (n = 1277) were randomly assigned to control (n = 641) or iron reduction (n = 636). Occurrence of new visceral malignancy and cause-specific mortality data were collected prospectively. Cancer and mortality outcomes in the two arms were compared using intent-to-treat analysis with a Cox proportional hazards regression model. Statistical tests were two-sided.Patients were followed up for an average of 4.5 years. Ferritin levels were similar in both groups at baseline but were lower in iron reduction patients than control patients across all 6-month visits (mean = 79.7 ng/mL, 95% confidence interval [CI] = 73.8 to 85.5 ng/mL vs 122.5 ng/mL, 95% CI = 115.5 to 129.5 ng/mL; P < .001). Risk of new visceral malignancy was lower in the iron reduction group than in the control group (38 vs 60, hazard ratio [HR] = 0.65, 95% CI = 0.43 to 0.97; P = .036), and, among patients with new cancers, those in the iron reduction group had lower cancer-specific and all-cause mortality (HR = 0.39, 95% CI = 0.21 to 0.72; P = .003; and HR = 0.49, 95% CI = 0.29 to 0.83; P = .009, respectively) than those in the control group. Mean ferritin levels across all 6-monthly visits were similar in patients in the iron reduction and control groups who developed cancer but were lower among all patients who did not develop cancer than among those who did (76.4 ng/mL, 95% CI = 71.4 to 81.4 ng/mL, vs 127.1 ng/mL, 95% CI = 71.2 to 183.0 ng/mL; P = .017).Iron reduction was associated with lower cancer risk and mortality. Further studies are needed to define the role of body iron in cancer risk.

  View details for DOI 10.1093/jnci/djn209

  View details for Web of Science ID 000257789000008

  View details for PubMedID 18612130

• Investigational antiangiogenesis agent limits AAA progression in mice 9th Annual Conference on Arteriosclerosis, Thrombosis and Vascular Biology Tedesco, M. M., Schultz, G. M., Asagami, T. M., Gerritsen, M. E., Dalman, R. L. LIPPINCOTT WILLIAMS & WILKINS. 2008: E138–E138

  View details for Web of Science ID 000256053400568

• Simulation-based endovascular skills assessment: The future of credentialing? 22nd Annual Meeting of the Western-Vascular-Society Tedesco, M. M., Pak, J. J., Harris, E. J., Krummel, T. M., Dalman, R. L., Lee, J. T. MOSBY-ELSEVIER. 2008: 1008–14

  Abstract

  Simulator-based endovascular skills training measurably improves performance in catheter-based image-guided interventions. The purpose of this study was to determine whether structured global performance assessment during endovascular simulation correlated well with trainee-reported procedural skill and prior experience level.Fourth-year and fifth-year general surgery residents interviewing for vascular fellowship training provided detailed information regarding prior open vascular and endovascular operative experience. The pretest questionnaire responses were used to separate subjects into low (<20 cases) and moderate (20 to 100) endovascular experience groups. Subjects were then asked to perform a renal angioplasty/stent procedure on the Procedicus Vascular Intervention System Trainer (VIST) endovascular simulator (Mentice Corporation, Gothenburg, Sweden). The subjects' performance was supervised and evaluated by a blinded expert interventionalist using a structured global assessment scale based on angiography setup, target vessel catheterization, and the interventional procedure. Objective measures determined by the simulator were also collected for each subject. A postsimulation questionnaire was administered to determine the subjects' self-assessment of their performance.Seventeen surgical residents from 15 training programs completed questionnaires before and after the exercise and performed a renal angioplasty/stent procedure on the endovascular simulator. The beginner group (n = 8) reported prior experience of a median of eight endovascular cases (interquartile range [IQR], 6.5-17.8; range, 4-20), and intermediate group (n = 9) had previously completed a median of 42 cases (IQR, 31-44; range, 25-89, P = .01). The two groups had similar prior open vascular experience (79 cases vs 75, P = .60). The mean score on the structured global assessment scale for the low experience group was 2.68 of 5.0 possible compared with 3.60 for the intermediate group (P = .03). Scores for subcategories of the global assessment score for target vessel catheterization (P = .02) and the interventional procedure (P = .05) contributed more to the differentiation between the two experience groups. Total procedure time, fluoroscopy time, average contrast used, percentage of lesion covered by the stent, placement accuracy, residual stenosis rates, and number of cine loops utilized were similar between the two groups (P > .05).Structured endovascular skills assessment correlates well with prior procedural experience within a high-fidelity simulation environment. In addition to improving endovascular training, simulators may prove useful in determining procedural competency and credentialing standards for endovascular surgeons.

  View details for DOI 10.1016/j.jvs.2008.01.007

  View details for Web of Science ID 000255294700019

  View details for PubMedID 18372149

• Medical management of small abdominal aortic aneurysms CIRCULATION Baxter, B. T., Terrin, M. C., Dalman, R. L. 2008; 117 (14): 1883-1889

  Abstract

  Abdominal aortic aneurysm is a common condition that may be lethal when it is unrecognized. Current guidelines suggest repair as the aneurysm diameter reaches 5.0 to 5.5 cm. Most aortic aneurysms are detected incidentally when imaging is done for other purposes or through screening programs. Ninety percent of these aneurysms are below the threshold for intervention at the time of detection. A number of studies have sought to determine factors that lead to progression of aneurysmal disease that might be amenable to intervention during this period of observation. We review these studies and make recommendations for the medical management of small abdominal aortic aneurysms. On the basis of our current knowledge of the causes of aneurysm, a number of approaches have been proposed to prevent progression of aneurysmal disease. These include hemodynamic management, inhibition of inflammation, and protease inhibition. The American College of Cardiology/American Heart Association clinical practice guidelines rules of evidence have helped to define strength of evidence to support these approaches. Level A evidence (from large randomized trials) is available to indicate that observation of small aneurysms in men is safe up to a size of 5.5 cm and that propranolol does not inhibit aneurysm expansion. Level B evidence (from small randomized trials) suggests that roxithromycin or doxycycline will decrease the rate of aneurysm expansion. A number of studies agree that tobacco use is associated with an increased rate of aneurysm expansion. Level B and C evidence is available to suggest that 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) may inhibit aneurysm expansion. There are animal data but no human data demonstrating that angiotensin-converting enzyme inhibitors or losartan, an angiotensin receptor blocker, will decrease the rate of AAA expansion. A pharmacological agent without important side effects that inhibited aneurysm expansion could change current approaches to aneurysm treatment. Additional studies are needed to clarify the potential role of doxycycline, roxithromycin, and statin therapy in the progression of aneurysmal disease.

  View details for DOI 10.1161/CIRCULATIONAHA.107.735274

  View details for Web of Science ID 000254754000014

  View details for PubMedID 18391122

• The three-dimensional micro- and nanostructure of the aortic medial lamellar unit measured using 3D confocal and electron microscopy imaging MATRIX BIOLOGY O'Connell, M. K., Murthy, S., Phan, S., Xu, C., Buchanan, J., Spilker, R., Dalman, R. L., Zarins, C. K., Denk, W., Taylor, C. A. 2008; 27 (3): 171-181

  Abstract

  Changes in arterial wall composition and function underlie all forms of vascular disease. The fundamental structural and functional unit of the aortic wall is the medial lamellar unit (MLU). While the basic composition and organization of the MLU is known, three-dimensional (3D) microstructural details are tenuous, due (in part) to lack of three-dimensional data at micro- and nano-scales. We applied novel electron and confocal microscopy techniques to obtain 3D volumetric information of aortic medial microstructure at micro- and nano-scales with all constituents present. For the rat abdominal aorta, we show that medial elastin has three primary forms: with approximately 71% of total elastin as thick, continuous lamellar sheets, 27% as thin, protruding interlamellar elastin fibers (IEFs), and 2% as thick radial struts. Elastin pores are not simply holes in lamellar sheets, but are indented and gusseted openings in lamellae. Smooth muscle cells (SMCs) weave throughout the interlamellar elastin framework, with cytoplasmic extensions abutting IEFs, resulting in approximately 20 degrees radial tilt (relative to the lumen surface) of elliptical SMC nuclei. Collagen fibers are organized as large, parallel bundles tightly enveloping SMC nuclei. Quantification of the orientation of collagen bundles, SMC nuclei, and IEFs reveal that all three primary medial constituents have predominantly circumferential orientation, correlating with reported circumferentially dominant values of physiological stress, collagen fiber recruitment, and tissue stiffness. This high resolution three-dimensional view of the aortic media reveals MLU microstructure details that suggest a highly complex and integrated mural organization that correlates with aortic mechanical properties.

  View details for DOI 10.1016/j.matbio.2007.10.008

  View details for Web of Science ID 000254993000003

  View details for PubMedID 18248974

  View details for PubMedCentralID PMC2679973

• Risk factors for developing postprocedural microemboli following carotid interventions JOURNAL OF ENDOVASCULAR THERAPY Tedesco, M. M., Coogan, S. M., Dalman, R. L., Haukoos, J. S., Lane, B., Loh, C., Penkar, T. S., Lee, J. T. 2007; 14 (4): 561-567

  Abstract

  To determine risk factors predictive of microemboli found on diffusion-weighted magnetic resonance imaging (DW-MRI) following carotid angioplasty and stenting (CAS) with distal protection and carotid endarterectomy (CEA).A retrospective review was conducted of all carotid interventions at a single institution between 2004 and 2006. In that time frame, 64 carotid interventions (34 CAS, 30 CEA) were performed in 63 male patients (mean age 69.5 years, range 52 to 91) with DW-MRI scans available for review. Patient characteristics, including age, gender, smoking history, diabetes mellitus, hypertension, hyperlipidemia, obesity (body mass index >30), coronary artery disease (CAD), chronic obstructive pulmonary disease, peripheral vascular disease, and atrial fibrillation, were documented. For the CAS patients, anatomical and procedural characteristics, including fluoroscopy time, contrast volume, performance of an arch angiogram, and lesion anatomy, were recorded. Bivariate analyses were performed to determine which parameters were associated with the occurrence of acute postprocedural microemboli found on DW-MRI by 2 blinded neuroradiologists.Twenty-four (71%) of the 34 CAS patients and 1 (3%) of the 30 CEA patients demonstrated new cerebral microemboli postoperatively. In the bivariate analyses of all patient, anatomical, and procedural characteristics, only a history of CAD was associated with an increased risk of microemboli; 20 (80%) of the 25 patients who had postprocedure microemboli had CAD compared to 18 (46%) of 39 patients without microemboli (p=0.007). Twenty (53%) of the 38 (59%) patients with CAD developed microemboli compared to 5 (19%) of the 26 patients without CAD (p=0.007). All other patient, procedural, and anatomical characteristics were not found to be independent risk factors predictive of postprocedure microemboli.CAS with distal protection carries a significantly greater risk for developing new microemboli compared to CEA. Of all the risk factors analyzed, only a history of CAD emerged as an independent risk factor for the development of microemboli following carotid intervention. This finding may influence the decision to perform CAS in patients deemed high risk solely due to the presence of CAD.

  View details for Web of Science ID 000248794300019

  View details for PubMedID 17696633

• Postprocedural microembolic events following carotid surgery and carotid angioplasty and stenting 21st Annual Meeting of the Western-Vascular-Society Tedesco, M. M., Lee, J. T., Dalman, R. L., Lane, B., Loh, C., Haukoos, J. S., Rapp, J. H., Coogan, S. M. MOSBY-ELSEVIER. 2007: 244–50

  Abstract

  The relative safety of percutaneous carotid interventions remains controversial. Few studies have used diffusion-weighted magnetic resonance imaging (DW-MRI) to evaluate the safety of these interventions. We compared the incidence and distribution of cerebral microembolic events after carotid angioplasty and stenting (CAS) with distal protection to standard open carotid endarterectomy (CEA) using DW-MRI.From November 2004 through August 2006, 69 carotid interventions (27 CAS, and 42 CEA) were performed in 68 males at a single institution. Pre- and postprocedure DW-MRI exams were obtained on each patient undergoing CAS and the 20 most recent CEA operations. These 46 patients (47 procedures as one patient underwent bilateral CEAs in a staged fashion) constitute our study sample, and the hospital records of these patients (27 CAS and 20 CEA) were retrospectively reviewed. The incidence and location of acute, postprocedural microemboli were determined using DW-MRIs and assessed independently by two neuroradiologists without knowledge of the subjects' specific procedure.Nineteen CAS patients (70%, 95% confidence interval [CI]: 42%-81%) demonstrated evidence of postoperative, acute, cerebral microemboli by DW-MRI vs none of the CEA patients (0%, 95% CI: 0%-17%) (P < .0001). Of the 19 CAS patients with postoperative emboli, nine (47%) were ipsilateral to the index carotid lesion, three (16%) contralateral, and seven (36%) bilateral. The median number of ipsilateral microemboli identified in the CAS group was 1 (interquartile ranges [IQR]: 0-2, range 0-21). The median number of contralateral microemboli identified in the CAS group was 0 (IQR: 0-1, range 0-5). Three (11%) CAS patients experienced temporary neurologic sequelae lasting less than 36 hours. These patients suffered 12 (six ipsilateral and six contralateral), 20 (19 ipsilateral and one contralateral), and zero microemboli, respectively. By univariate analysis, performing an arch angiogram prior to CAS was associated with a higher risk of microemboli (median microemboli 5 vs none, P =.04)Although our early experience suggests that CAS may be performed safely (no permanent neurologic deficits following 27 consecutive procedures), cerebral microembolic events occurred in over two-thirds of the procedures despite the uniform use of distal protection. Open carotid surgery in this series seems to offer a lower risk of periprocedural microembolic events detected by DW-MRI.

  View details for DOI 10.1016/j.j.jvs.2007.04.049

  View details for Web of Science ID 000248395600014

  View details for PubMedID 17600657

• Variable growth rates and diameter-dependent expression of vascular endothelial growth factor receptors in experimental abdominal aortic aneurysms 8th Annual Conference on Arteriosclerosis, Thrombosis, and Vascular Biology Tedesco, M. M., Terashima, M., Blankenberg, F. G., Levashova, Z., Backer, M., Backer, J., Sho, M., Sho, E., McConnell, M. V., Dalman, R. L. LIPPINCOTT WILLIAMS & WILKINS. 2007: E37–E38

  View details for Web of Science ID 000246714600051

• Reduction of iron stores and cardiovascular outcomes in patients with peripheral arterial disease - A randomized controlled trial JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Zacharski, L. R., Chow, B. K., Howes, P. S., Shamayeva, G., Baron, J. A., Dalman, R. L., Malenka, D. J., Ozaki, C. K., Lavori, P. W. 2007; 297 (6): 603-610

  Abstract

  Accumulation of iron in excess of physiologic requirements has been implicated in risk of cardiovascular disease because of increased iron-catalyzed free radical-mediated oxidative stress.To test the hypothesis that reducing body iron stores through phlebotomy will influence clinical outcomes in a cohort of patients with symptomatic peripheral arterial disease (PAD). Design, Setting, andMulticenter, randomized, controlled, single-blinded clinical trial based on the Iron (Fe) and Atherosclerosis Study (FeAST) (VA Cooperative Study #410) and conducted between May 1, 1999, and April 30, 2005, within the Department of Veterans Affairs Cooperative Studies Program and enrolling 1277 patients with symptomatic but stable PAD. Those with conditions likely to cause acute-phase increase of the ferritin level or with a diagnosis of visceral malignancy within the preceding 5 years were excluded. Analysis was by intent-to-treat.Patients were assigned to a control group (n = 641) or to a group undergoing reduction of iron stores by phlebotomy with removal of defined volumes of blood at 6-month intervals (avoiding iron deficiency) (n = 636), stratified by hospital, age, and baseline smoking status, diagnosis of diabetes mellitus, ratio of high-density to low-density lipoprotein cholesterol level, and ferritin level.The primary end point was all-cause mortality; the secondary end point was death plus nonfatal myocardial infarction and stroke.There were no significant differences between treatment groups for the primary or secondary study end points. All-cause deaths occurred in 148 patients (23%) in the control group and in 125 (20%) in the iron-reduction group (hazard ratio (HR), 0.85; 95% confidence interval (CI), 0.67-1.08; P = .17). Death plus nonfatal myocardial infarction and stroke occurred in 205 patients (32%) in the control group and in 180 (28%) in the iron-reduction group (HR, 0.88; 95% CI, 0.72-1.07; P = .20).Reduction of body iron stores in patients with symptomatic PAD did not significantly decrease all-cause mortality or death plus nonfatal myocardial infarction and stroke.Clinicaltrials.gov Identifier: NCT00032357.

  View details for Web of Science ID 000244177400023

  View details for PubMedID 17299195

• Hemodynamics in human abdominal aortic aneurysms during rest and simulated exercise ASME Summer Bioengineering Conference Les, A. S., Cheng, C. P., Blomme, M. T., Figueroa, C. A., LaDisa, J. F., Park, J. M., Herfkens, R. J., Dalman, R. L., Taylor, C. A. AMER SOC MECHANICAL ENGINEERS. 2007: 169–170

  View details for Web of Science ID 000252105700085

• Aortoiliac hemodynamic and morphologic adaptation to chronic spinal cord injury 20th Annual Meeting of the Western-Vascular-Society Yeung, J. J., Kim, H. J., Abbruzzese, T. A., Vignon-Clementel, I. E., Draney-Blomme, M. T., Yeung, K. K., Perkash, I., Herfkens, R. J., Taylor, C. A., Dalman, R. L. MOSBY-ELSEVIER. 2006: 1254–65

  Abstract

  Reduced lower limb blood flow and resistive hemodynamic conditions potentially promote aortic inflammation and aneurysmal degeneration. We used abdominal ultrasonography, magnetic resonance imaging, and computational flow modeling to determine the relationship between reduced infrarenal aortic blood flow in chronic spinal cord injury (SCI) subjects and risk for abdominal aortic aneurysm (AAA) disease.Aortic diameter in consecutive SCI subjects (n = 123) was determined via transabdominal ultrasonography. Aortic anatomic and physiologic data were acquired via magnetic resonance angiography (MRA; n = 5) and cine phase-contrast magnetic resonance flow imaging (n = 4) from SCI subjects whose aortic diameter was less than 3.0 cm by ultrasonography. Computational flow models were constructed from magnetic resonance data sets. Results were compared with those obtained from ambulatory control subjects (ultrasonography, n = 129; MRA/phase-contrast magnetic resonance flow imaging, n = 6) who were recruited at random from a larger pool of risk factor-matched individuals without known AAA disease.Age, sex distribution, and smoking histories were comparable between the SCI and control groups. In the SCI group, time since injury averaged 26 +/- 13 years (mean +/- SD). Aortic diameter was larger (P < .01), and the prevalence of large (> or = 2.5 cm; P < .01) or aneurysmal (> or = 3.0 cm; P < .05) aortas was greater in SCI subjects. Paradoxically, common iliac artery diameters were reduced in SCI subjects (< 1.0 cm; 48% SCI vs 26% control; P < .0001). Focal preaneurysmal enlargement was noted in four of five SCI subjects by MRA. Flow modeling revealed normal flow volume, biphasic and reduced oscillatory flow, slower pressure decay, and reduced wall shear stress in the SCI infrarenal aorta.Characteristic aortoiliac hemodynamic and morphologic adaptations occur in response to chronic SCI. Slower aortic pressure decay and reduced wall shear stress after SCI may contribute to mural degeneration, enlargement, and an increased prevalence of AAA disease.

  View details for DOI 10.1016/j.jvs.2006.08.026

  View details for Web of Science ID 000242564400022

  View details for PubMedID 17145427

• Enhanced abdominal aortic aneurysm formation in procarboxypeptidase B-deficient mice 79th Annual Scientific Session of the American-Heart-Association Tedesco, M. M., Sho, E., Nishimura, T., Sho, M., Dalman, R. L., Leung, L. L. LIPPINCOTT WILLIAMS & WILKINS. 2006: 39–40

  View details for Web of Science ID 000241792800203

• Allometric scaling of wall shear stress from mice to humans: quantification using cine phase-contrast MRI and computational fluid dynamics AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY Greve, J. M., Les, A. S., Tang, B. T., Blomme, M. T., Wilson, N. M., Dalman, R. L., Pelc, N. J., Taylor, C. A. 2006; 291 (4): H1700-H1708

  Abstract

  Allometric scaling laws relate structure or function between species of vastly different sizes. They have rarely been derived for hemodynamic parameters known to affect the cardiovascular system, e.g., wall shear stress (WSS). This work describes noninvasive methods to quantify and determine a scaling law for WSS. Geometry and blood flow velocities in the infrarenal aorta of mice and rats under isoflurane anesthesia were quantified using two-dimensional magnetic resonance angiography and phase-contrast magnetic resonance imaging at 4.7 tesla. Three-dimensional models constructed from anatomic data were discretized and used for computational fluid dynamic simulations using phase-contrast velocity imaging data as inlet boundary conditions. WSS was calculated along the infrarenal aorta and compared between species to formulate an allometric equation for WSS. Mean WSS along the infrarenal aorta was significantly greater in mice and rats compared with humans (87.6, 70.5, and 4.8 dyn/cm(2), P < 0.01), and a scaling exponent of -0.38 (R(2) = 0.92) was determined. Manipulation of the murine genome has made small animal models standard surrogates for better understanding the healthy and diseased human cardiovascular system. It has therefore become increasingly important to understand how results scale from mouse to human. This noninvasive methodology provides the opportunity to serially quantify changes in WSS during disease progression and/or therapeutic intervention.

  View details for DOI 10.1152/ajpheart.00274.2006

  View details for Web of Science ID 000240509700025

  View details for PubMedID 16714362

• Flow-mediated effects on abdominal aortic aneurysms. Future cardiology Tedesco, M. M., Dalman, R. L. 2006; 2 (4): 477-482

  Abstract

  Abdominal aortic aneurysms (AAAs) are a common and lethal disease of the elderly. 'Atherosclerotic' aneurysms occur far more frequently in the caudal or infrarenal segment, a localization influenced at least in part by site-specific hemodynamic conditions. Alterations in aortic flow and wall shear stress modify AAA disease progression in small animal models and may explain increased prevalence in certain at-risk patient populations. If a specific hemodynamic risk profile can be established, anti-aneurysmal lower extremity exercise protocols or the development of molecular interventions that mimic the benefits induced by exercise may prove effective in reducing progression of small AAAs or limiting continued remodeling or expansion following endovascular exclusion.

  View details for DOI 10.2217/14796678.2.4.477

  View details for PubMedID 19804182

• AAA disease - Mechanism, stratification, and treatment Conference on the Abdominal Aortic Aneurysm Dalman, R. L., Tedesco, M. M., Myers, J., Taylor, C. A. WILEY-BLACKWELL. 2006: 92–109

  Abstract

  Abdominal aortic aneurysm (AAA) is a common and frequently lethal disease of older Americans. No medical therapy has been proven effective in retarding progression of small AAAs prior to surgical repair. With the emerging ability of magnetic resonance (MR) flow imaging and MR-based computational analysis to define aortic hemodynamic conditions, and bio-imaging strategies to monitor aortic inflammation real time in vivo, the opportunity now exists to confirm the potential value of medical interventions such as supervised exercise training as first line therapy for small AAA disease.

  View details for DOI 10.1096/annals.1383.008

  View details for Web of Science ID 000244109700010

  View details for PubMedID 17182926

• Comparison of cell-type-specific vs transmural aortic gene expression in experimental aneurysms JOURNAL OF VASCULAR SURGERY Sho, E., Sho, M., Nanjo, H., Kawamura, K., Masuda, H., Dalman, R. L. 2005; 41 (5): 844-851

  Abstract

  Abdominal aortic aneurysm (AAA) progression and disease resistance are related to mural cellularity; adventitial macrophages and neocapillaries predominate in larger, advanced aneurysms, whereas smaller AAAs have fewer macrophages and retain more medial smooth muscle cells (SMCs). Expression analysis of mRNA derived from the entire aorta may mask the role that specific cell types play in modulating disease progression. We used laser capture microdissection (LCM) to isolate SMC and macrophage-predominant mural cell populations for gene expression analysis in variable-flow AAA.Rat AAAs were created via porcine pancreatic elastase (PPE) infusion. Aortic flow was increased via femoral arteriovenous fistula creation (HF-AAA) or reduced via unilateral iliac ligation (LF-AAA) in selected cohorts. SMC and macrophage-predominant cell populations were isolated via LCM and analyzed for expression of pro-inflammatory transcription factors and chemokines, cytokines, and proteolytic enzymes via real-time polymerase chain reaction.Aortic PPE infusion precipitated endothelial cell (EC) denudation, SMC apoptosis, and elastic lamellar degeneration. Increased aortic flow (HF > NF > LF) stimulated restorative EC and SMC proliferation (45.8 +/- 6.6 > 30.5 +/- 2.1 > 21 +/- 3.6 and 212.2 +/- 9.8 > 136.5 +/- 8.9 > 110 +/- 13.5, respectively, for both cell types; P < .05) at 5 days after PPE infusion, while simultaneously reducing medial SMC apoptosis and transmural macrophage infiltration. Expression of nuclear factor kappa B (NF-kappab), granulocyte macrophage-colony stimulating factor (GM-CSF), macrophage migration inhibitory (MIF), heparin-binding EGF-like factor (HB-EGF) and inducible nitric oxide synthase (iNOS) varied between cell types and flow conditions at all time points examined. Gelatinolytic protease expression varied by cell type in response to flow loading (eg, increased in SMCs, decreased in macrophages), consistent with observed patterns of elastolysis and SMC proliferation reported in prior experiments.Flow differentially regulates cell-specific AAA gene expression. Whole-organ analysis of AAA tissue lysates obscures important cellular responses to inflammation and flow, and may explain previous seemingly contradictory observations regarding proteolysis and cell proliferation. Cell-type specific expression and functional analyses may substantially clarify the pathophysiology of AAA disease.Understanding aneurysmal aortic degeneration at the most fundamental level is a critical precursor to the development of next-generation therapies such as drug-eluting endografts and/or medical therapies to limit expansion of preclinical AAA in high-risk or elderly patients. Although animal modeling is necessary to gain insight into the early initiating events of AAA disease, the methods used in such analyses have critical bearing on the conclusions drawn regarding pathogenesis and potential therapeutic derivations. By analyzing cell-type-specific gene expression rather than whole-organ tissue lysates, the precise roles of important mediators such as metalloproteinases can be placed in the appropriate context. Further refinement of these techniques may allow cell-specific therapies to be applied at defined time points in disease progression with improved patient outcome and reduced procedural morbidity.

  View details for DOI 10.1016/j.jvs.2005.02.027

  View details for Web of Science ID 000229092300019

  View details for PubMedID 15886670

• Hemodynamic regulation of CD34(+) cell localization and differentiation in experimental aneurysms ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY Sho, E., Sho, M., Nanjo, H., Kawamura, K., Masuda, H., Dalman, R. L. 2004; 24 (10): 1916-1921

  Abstract

  Bone marrow-derived vascular progenitor cells (CD34+) are present in human and animal models of abdominal aortic aneurysm (AAA) disease. These preterminally differentiated cells may modulate disease resistance. We examined the influence of variable hemodynamic conditions on progenitor cell localization and differentiation in experimental AAAs.Murine AAAs were created via porcine pancreatic elastase (PPE) infusion. AAA blood flow was increased by aortocaval fistula (ACF) formation (HF-AAA), decreased via left iliac ligation (LF-AAA), or left unchanged (NF-AAA). ACF creation increased flow by 1700%, whereas iliac ligation decreased flow 79% compared with baseline (0.6+/-0.1 mL/min). Wall shear stress (WSS) increased or decreased accordingly, and remained elevated (9.2+/-2.0 dynes/cm2) in HF-AAA 14 days after PPE infusion. CD34+ cells were identified throughout the aortic wall in all flow conditions. Seven days after PPE infusion, HF-AAAs had more CD34+ cells than LF-AAA (187+/-10 versus 155+/-7 CD34+ cells/cross sectional, P<0.05), more medial smooth muscle cells, fewer infiltrative macrophages, and a smaller diameter than LF-AAA. LF-AAAs also contained more adventitial capillaries (CD34+ capillaries 181+/-12 versus 89+/-32/cross-sectional area in HF-AAA, P<0.05). The total progenitor cell/capillary index (CD34+ capillary plus CD31+ capillary/cross sectional area) was higher in LF-AAA (282+/-31 versus 129+/-47, P<0.05). Vascular endothelial (VEGF) and platelet-derived growth factor (PDGF) expression varied directly with capillary density between groups. Increased granulocyte-macrophage colony-stimulating factor (GM-CSF) expression was also present in LF-AAAs.Hemodynamic conditions influence CD34+ cell localization and differentiation in experimental AAA. Adventitial capillary angiogenesis may augment inflammation and disease progression. Modulating cell lineage differentiation of mature progenitor cells may represent a novel therapeutic strategy to maintain medial cellularity and extracellular matrix integrity in AAA disease.

  View details for DOI 10.1161/01.ATV.0000142805.20398.74

  View details for Web of Science ID 000224326200030

  View details for PubMedID 15319272

• Aortic wall cell proliferation via basic fibroblast growth factor gene transfer limits progression of experimental abdominal aortic aneurysm JOURNAL OF VASCULAR SURGERY Hoshina, K., Koyama, H., Miyata, T., Shigematsu, H., Takato, T., Dalman, R. L., Nagawa, H. 2004; 40 (3): 512-518

  Abstract

  Our previous study demonstrated that high flow conditions stimulated cell proliferation in the aortic wall in a rat model of abdominal aortic aneurysm (AAA), and we speculated that there is a possible relation between medial cell density and aortic wall integrity. In the present study we delivered the basic fibroblast growth factor (bFGF) gene to the aortic wall of a rat AAA model and evaluated the effects of growth factor-enhanced smooth muscle cell (SMC) proliferation on aneurysm progression.AAA was induced in rats by means of infusion of porcine pancreatic elastase. Immediately after elastase infusion the abdominal aorta was filled with an expression plasmid vector containing the bFGF gene (bFGF group) or LacZ gene (control group); then gene transfer to the aortic wall was carried out with an in vivo electroporation method. The animals were killed 7 days after treatment, and the aneurysm was measured. The numbers of SMCs, macrophages, and endothelial cells were counted with immunostaining, and cell replication was evaluated with bromodeoxyuridine (BrdU) staining.Aneurysm diameter in the bFGF group was significantly smaller than that in the control group (4.6 +/- 0.3 mm vs 6.5 +/- 1.4 mm; P <.01). The numbers of medial SMCs and BrdU-incorporated cells in the bFGF group were significantly greater than those in the control group (SMC, 101 +/- 34 per high-power field [hpf] vs 80 +/- 31/hpf; P <.05, BrdU, 107 +/- 63/hpf vs 50 +/- 33/hpf; P <.05), whereas no difference was detected in the numbers of macrophages and endothelial cells between the 2 groups.Delivery of bFGF to the aortic wall induced significant enhancement of medial SMC proliferation, without an increase in inflammatory infiltration, then successfully limited aneurysm enlargement. These findings suggest that increased medial cellularity inhibits aneurysm formation, which possibly offers a clue for developing a new strategy for treatment of AAAs.

  View details for DOI 10.1016/j.jva.2004.06.018

  View details for Web of Science ID 000227388200021

  View details for PubMedID 15337882

• Continuous periaortic infusion improves doxycycline efficacy in experimental aortic aneurysms 18th Annual Meeting of the Western-Vascular-Society Sho, E., Chu, J., Sho, M., Fernandes, B., Judd, D., Ganesan, P., Kimura, H., Dalman, R. L. MOSBY-ELSEVIER. 2004: 1312–21

  Abstract

  We created a novel continuous infusion system to evaluate the efficacy of juxta-aortic doxycycline delivery as a transitional step toward developing hybrid drug/device treatment strategies for abdominal aortic aneurysm (AAA) disease.Controlled comparison of treatment outcomes was studied in animal models with molecular and morphologic tissue analysis in a collaboration between university and corporate research laboratories. Rat AAAs were created via porcine pancreatic elastase (PPE) infusion and grouped and analyzed by subsequent treatment status (either doxycycline in vehicle or vehicle alone) and drug delivery method (continuous infusion via periaortic delivery system [PDS] or twice-daily subcutaneous injection). The main outcome measures were AAA diameter via direct measurement, medial elastin lamellar preservation via light microscopy, mural smooth muscle cell (SMC) proliferation and SMC and macrophage density via immunostaining and counting, expression of matrix metalloproteinases 2, 9, and 14 and tissue inhibitors of metalloproteinases 1 and 2 via real-time reverse transcriptase-polymerase chain reaction, and enzymatic activity via substrate zymography. Serum drug levels were analyzed via liquid chromatography/mass spectroscopy.PDS (1.5 mg/kg/day) and subcutaneous (60 mg/kg/day) delivery methods caused comparable reductions in AAA diameter during the period of 14 days after PPE infusion. PDS rats gained more weight during the postoperative period (P <.001), possibly as a result of reduced serum drug levels and systemic toxicity. Doxycycline treatment reduced AAA macrophage infiltration and SMC proliferation significantly. Despite reduced diameter, circumferential elastic lamellar preservation was not apparent in doxycycline-treated AAAs.Continuous periaortic infusion lowers the effective doxycycline dose for experimental AAA limitation. Alternative biologic inhibition strategies might also be amenable to direct intra-aortic or juxta-aortic delivery. Periaortic infusion might improve the clinical outcome of minimally invasive AAA treatment strategies. Clinical relevance Aneurysm remodeling may continue after successful endovascular AAA exclusion. Continued proteolytic activity within the aneurysm wall potentiates late graft migration and failure. The doxycycline infusion system developed in these experiments may serve as a prototype for adjuvant treatment modalities that complement endovascular AAA exclusion. Local delivery of doxycycline or other agents active in AAA disease, either continuously or at selected intervals after graft implantation, may stabilize the wall and aid in maintaining aneurysm exclusion. Alternative delivery methods could include passive diffusion from either the graft material itself or treatment reservoirs incorporated into endografts. Given the recognized limitations of current technologies, adjuvant biologic therapies have the potential to improve long-term patient outcome significantly after endovascular exclusion.

  View details for DOI 10.1016/j.jvs.2004.01.036

  View details for Web of Science ID 000222018600026

  View details for PubMedID 15192574

• Hemodynamic forces regulate mural macrophage infiltration in experimental aortic aneurysms EXPERIMENTAL AND MOLECULAR PATHOLOGY Sho, E., Sho, M., Hoshina, K., Kimura, H., Nakahashi, T. K., Dalman, R. L. 2004; 76 (2): 108-116

  Abstract

  Blood flow (BF) and wall shear stress (WSS) influence reactive oxygen species production and oxidative stress in abdominal aortic aneurysm (AAA) disease. To gain further insight into the mechanisms of hemodynamic influences on AAA inflammation, we examined aneurysm macrophage density, chemotaxis and survival under varying aortic flow conditions. Rat AAAs were created via porcine pancreatic elastase (PPE) infusion. In selected cohorts, AAA flow was increased via left common femoral arteriovenous fistula (AVF) creation (HF-AAA) or decreased by left common iliac ligation (LF-AAA). WSS was highest in HF-AAA (10.4 +/- 2.3 dyn/cm(2) vs. 2.4 +/- 0.4 and 0.5 +/- 0.2 for NF- and LF-AAA, respectively, P < 0.001) 7 days after PPE infusion, with reduced medial macrophage density and increased apoptosis. Adventitial macrophage density was not significantly influenced by flow. Monocyte chemoattractant protein-1 (MCP-1) and granulocyte-macrophage colony-stimulating factor (GM-CSF) gene expression correlated with observed macrophage densities in the media and adventitia. Luminal flow conditions regulate AAA inflammation in part via influences on medial macrophage density. Hemodynamic forces may modulate AAA inflammation and diameter enlargement via direct regulation of intimal macrophage adhesion, transmural migration or survival.

  View details for DOI 10.1016/j.yexmp.2003.11.003

  View details for Web of Science ID 000220279000004

  View details for PubMedID 15010288

• Oxidative stress and abdominal aneurysms: how aortic hemodynamic conditions may influence AAA disease CARDIOVASCULAR SURGERY Dalman, R. L. 2003; 11 (5): 417-419

  View details for DOI 10.1016/S0967-2109(03)00075-9

  View details for Web of Science ID 000185810200015

  View details for PubMedID 12958555

• Wall shear stress and strain modulate experimental aneurysm cellularity 17th Annual Meeting of the Western-Vascular-Society Hoshina, K., Sho, E., Sho, M., Nakahashi, T. K., Dalman, R. L. MOSBY-ELSEVIER. 2003: 1067–74

  Abstract

  Clinical evidence indicates that hemodynamic conditions influence abdominal aortic aneurysm (AAA) disease. We modified blood flow to evaluate the effects of wall shear stress (WSS) and relative wall strain (RWS) on aneurysm structure and cellularity.Rodent AAAs were created with porcine pancreatic elastase infusion. In group 1 AAA WSS was increased with left femoral arteriovenous fistula creation, whereas in group 2 AAA WSS was decreased with left iliac artery ligation. Aortic flow, wall motion, and blood pressure were recorded in both groups. AAA diameter, endothelial and smooth muscle cellularity (CD31 and alpha-smooth muscle actin immunostaining), markers for cell proliferation (5-bromodeoxyuridine), endothelial and smooth muscle cell growth factor production (vascular endothelial growth factor-D and platelet-derived growth factor-beta, respectively), and apoptosis (deoxyuridine triphosphate nick end-labeled [TUNEL] stain) were compared between groups when the animals were killed.Arteriovenous fistula creation increased WSS (high-flow AAA) by 300% and RWS by 150%. Iliac ligation reduced WSS (low-flow AAA) by 60%. Neither procedure significantly altered systolic, diastolic, or mean aortic pressure. When the animals were killed 7 days after elastase infusion, low-flow AAAs were significantly larger than high-flow AAAs. High-flow AAAs also contained more endothelial cells and smooth muscle cells, and evidence of increased growth factor production, cell proliferation, and decreased apoptosis. No difference in type or severity of AAA inflammatory cell infiltrate was noted between groups.High flow conditions stimulate endothelial cell and smooth muscle cell proliferation in experimental aneurysms. Enhanced cellularity may stabilize aortic integrity, limiting aneurysm growth. Increased lower extremity activity may prevent or retard AAA disease through salutary effects on aortic remodeling mediated by endothelial cells and smooth muscle cells.

  View details for DOI 10.1067/mva.2003.169

  View details for Web of Science ID 000182724700031

  View details for PubMedID 12756356

• Flow loading induces macrophage antioxidative gene expression in experimental aneurysms ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY Nakahashi, T. K., Hoshina, K., Tsao, P. S., Sho, E., Sho, M., Karwowski, J. K., Yeh, C., Yang, R. B., Topper, J. N., Dalman, R. L. 2002; 22 (12): 2017-2022

  Abstract

  Reactive oxygen species may act as proinflammatory mediators in abdominal aortic aneurysm (AAA) disease. Flow loading increases antioxidative enzyme expression and limits reactive oxygen species production in vascular smooth muscle cells in vitro, limits experimental AAA enlargement in rodent models, and is indirectly associated with reduced clinical AAA risk. We attempted to determine the mechanism or mechanisms by which flow loading limits AAA enlargement.Rodent AAAs were flow loaded via femoral arteriovenous fistula creation. Aortic wall shear stress and relative wall strain were significantly higher in flow-loaded rodents. Flow loading reduced AAA diameter by 26% despite evidence of flow-mediated aortic enlargement proximal to the aneurysmal segment. Messenger RNA from AAA tissue was harvested for cDNA labeling and hybridization to a 384-clone DNA microarray. Twenty-nine genes were differentially expressed (relative intensity/relative intensity of control ratio >1.5 and <0.67) in flow-loaded compared with normal flow AAA tissue, including heme oxygenase 1 (HO-1). Increased HO-1 expression was confirmed via reverse transcriptase-polymerase chain reaction. Immunohistochemistry localized HO-1 expression to infiltrative macrophages. alpha-Tocopherol was found to be as effective as flow loading in limiting AAA enlargement. Flow loading and alpha-tocopherol therapy reduced AAA reactive oxygen species production.Flow loading may attenuate AAA enlargement via wall shear or strain-related reductions in oxidative stress.

  View details for DOI 10.1161/01.ATV.0000042082.38014.EA

  View details for Web of Science ID 000180046000014

  View details for PubMedID 12482828

• Transition to all-autogenous hemodialysis access: The role of preoperative vein mapping 12th Annual Winter Meeting of the Peripheral-Vascular-Surgery-Society Dalman, R. L., Harris, E. J., Victor, B. J., Coogan, S. M. ELSEVIER SCIENCE INC. 2002: 624–30

  Abstract

  Safe, reliable, and efficient hemodialysis access (DA) remains an unrealized ideal. Autogenous dialysis access (ADA) may improve outcome for renal failure patients. We now place ADA in 9 out of 10 new patients in an effort to maximize primary patency and minimize access-related complications. We reviewed our recent DA experience to determine whether our increased reliance on autogenous access (ADA) has improved outcomes, and to evaluate the impact of preoperative duplex venous imaging (vein mapping) on early and intermediate results. We conducted a retrospective database review of 108 consecutive patients undergoing initial permanent DA between 10/97 and 8/01. Mean follow-up was 13.1 months. Our results showed that increased ADA utilization decreases the need for secondary access procedures. The functional superiority of ADA vs. prosthetic dialysis access (PDA) in this series may be due to optimal autogenous conduit selection facilitated by preoperative vein mapping.

  View details for DOI 10.1007/s10016-001-0268-4

  View details for Web of Science ID 000178871800018

  View details for PubMedID 12203002

• Aneurysm-related death: Primary endpoint analysis for comparison of open and endovascular repair Joint Annual Meeting of the American-Association-for-Vascular-Surgery/Society-for-Vascular-Surgery Arko, F. R., Lee, W. A., Hill, B. B., Olcott, C., Dalman, R. L., Harris, E. J., Cipriano, P., Fogarty, T. J., Zarins, C. K. MOSBY-ELSEVIER. 2002: 297–304

  Abstract

  The purpose of this study was to utilize an objective endpoint analysis of aneurysm treatment, which is based on the primary objective of aneurysm repair, and to apply it to a consecutive series of patients undergoing open and endovascular repair.Aneurysm-related death was defined as any death that occurred within 30 days of primary aneurysm treatment (open or endovascular), within 30 days of a secondary aneurysm or graft-related treatment, or any death related to the aneurysm or graft at any time following treatment. We reviewed 417 consecutive patients undergoing elective infrarenal aortic aneurysm repair: 243 patients with open repair and 174 patients with endovascular repair.There was no difference between the groups (open vs endovascular) with regard to mean age +/- standard deviation (73 +/- 8 years vs 74 +/- 8 years) or aneurysm size (64 +/- 2 mm vs 58 +/- 10 mm) (P = not significant [NS]). The 30-day mortality for the primary procedure after open repair was 3.7% (9/243) and after endovascular repair was 0.6% (1/174, P <.05). The 30-day mortality for secondary procedures after open repair was 14% (6/41) compared to 0% after endovascular repair (P <.05). The aneurysm-related death rate was 4.1% (10/243) after open surgery and 0.6% (1/174) after endovascular repair (P <.05). Mean follow-up was 5 months longer following open repair (P <.05). Secondary procedures were performed in 41 patients following open surgery and 27 patients following endovascular repair (P = NS). Secondary procedures following open repair were performed for anastomotic aneurysms (n = 18), graft infection (n = 6), aortoenteric fistula (n = 5), anastomotic hemorrhage (n = 4), lower extremity amputation (n = 4), graft thrombosis (n = 3), and distal revascularization (n = 1). Secondary procedures following endovascular repair consisted of proximal extender cuffs (n = 11), distal extender cuffs (n = 11), limb thrombosis (n = 3), and surgical conversion (n = 2). The magnitude of secondary procedures following open repair was greater with longer operative time 292 +/- 89 minutes vs 129 +/- 33 minutes (P <.0001), longer length of stay 13 +/- 10 days vs 2 +/- 2 days (P <.0001) and greater blood loss 3382 +/- 4278 mL vs 851 +/- 114 mL (P <.0001).The aneurysm-related death rate combines early and late deaths and should be used as the primary outcome measure to objectively compare the results of open and endovascular repair in the treatment of infrarenal abdominal aortic aneurysms. In our experience, endovascular aneurysm repair reduced the overall aneurysm-related death rate when compared to open repair. Secondary procedures are required after both open and endovascular repair. However, the magnitude, morbidity, and mortality of secondary procedures are reduced significantly with endovascular repair.

  View details for DOI 10.1067/mva.2002.126314

  View details for Web of Science ID 000177489000015

  View details for PubMedID 12170210

• Open versus endovascular AAA repair in patients who are morphological candidates for endovascular treatment JOURNAL OF ENDOVASCULAR THERAPY Hill, B. B., Wolf, Y. G., Lee, W. A., Arko, F. R., Olcott, C., Schubart, P. J., Dalman, R. L., Harris, E. J., Fogarty, T. J., Zarins, C. K. 2002; 9 (3): 255-261

  Abstract

  To compare the outcomes of open versus endovascular repair of abdominal aortic aneurysm (AAA) in a cohort of patients who fulfill morphological criteria for endovascular repair.A retrospective review of 229 consecutive AAA patients treated over a 3-year period identified 149 patients who were candidates for endovascular repair based on preoperative computed tomography and angiography. Of the 149 patients, 79 (68 men; mean age 74 +/- 8 years) underwent endovascular repair with the AneuRx stent-graft; the remaining 70 (56 men; mean age 72 +/- 8 years) had open repair. Short-term outcome measures were 30-day mortality and procedure-related morbidity, length of stay in the intensive care unit and hospital, intraoperative blood loss, interval to oral diet, and time to ambulation. Long-term outcome measures included death and secondary procedures.There was no difference in the 30-day mortality between endovascular repair (2, 2.5%) and open repair (2, 2.9%), even though endovascular patients had more comorbidities (p<0.05). Overall length of stay was reduced for endovascular patients (3.9 +/- 2.4 days versus 7.7 +/- 3.1 days for surgical patients, p<0.0001). Fewer endograft patients had complications (24% versus 40% for open repair, p<0.05), and the severity of these complications was less, as evidenced by the shorter hospital stays for endovascular patients with complications compared to conventionally treated patients with complications (6.7 +/- 2.4 days versus 22.5 +/- 35.2 days, p<0.05). There were no aneurysm ruptures or late surgical conversions in either group.Patients with AAA who were endograft candidates but who were treated with open repair experienced more morbidity and had more complications than patients treated with stent-grafts. Despite increased comorbidities in the endograft patients, there was no increase in mortality compared to open repair. Both treatments required secondary procedures and appeared to be equally effective in preventing aneurysm rupture up to 3 years.

  View details for Web of Science ID 000176993800001

  View details for PubMedID 12096937

• Treatment of abdominal aortic anastomotic pseudoaneurysm with percutaneous coil embolization JOURNAL OF VASCULAR SURGERY Fann, J. I., Samuels, S., Slonim, S., Burdon, T. A., Dalman, R. L. 2002; 35 (4): 811-814

  Abstract

  Intraabdominal anastomotic pseudoaneurysms continue to be a late complication of aortic reconstructive procedures. Early surgical repair is critical but is associated with high operative mortality rates. We present a patient who was diagnosed with a distal anastomotic pseudoaneurysm 13 months after transabdominal repair of a symptomatic abdominal aortic aneurysm. Because of the poor operative risk, the patient was considered for a less invasive approach and underwent coil embolization of the abdominal aortic anastomotic pseudoaneurysm. The patient remains without recurrence of pseudoaneurysm 3.5 years later.

  View details for DOI 10.1067/mva.2002.121744

  View details for Web of Science ID 000175366300033

  View details for PubMedID 11932686

• Impact of endovascular repair on open aortic aneurysm surgical training 13th Annual Meeting of the American-Venous-Forum Arko, F. R., Lee, W. A., Hill, B. B., Olcott, C., Harris, E. J., Dalman, R. L., Fogarty, T. J., Zarins, C. K. MOSBY-ELSEVIER. 2001: 885–90

  Abstract

  The purpose of this study was to determine the impact of an endovascular stent-graft program on vascular training in open aortic aneurysm surgery.The institutional and vascular surgery fellow experience in aortic aneurysm repair during a 6-year period was reviewed. The 3-year period before introduction of endovascular repair was compared with the 3-year period after introduction of endovascular repair. All patients undergoing abdominal aortic aneurysm (AAA) or thoracoabdominal aortic aneurysm repairs were entered prospectively into a vascular registry and retrospectively analyzed to evaluate the changing patterns in aortic aneurysm treatment and surgical training.Between July 1994 and June 2000, a total of 588 patients with AAA or thoracoabdominal aneurysms were treated at Stanford University Medical Center. There were 296 (50%) open infrarenal AAA repairs, 87 (15%) suprarenal AAA repairs, 47 (8%) thoracoabdominal aneurysm repairs, and 153 (26%) endovascular stent-grafts. The total number of aneurysms repaired per year by vascular fellows before the endovascular program was 71.3 +/- 4.9 (range, 68-77) and increased to 124.7 +/- 35.6 (range, 91-162) after introduction of endovascular repair (P <.05). This increase was primarily caused by the addition of endovascular stent-graft repairs by vascular fellows (51.0 +/- 29.0/year [range, 23-81]). There was no change in the number of open infrarenal aortic aneurysm repairs per year, 53.0 +/- 6.6 (range, 48-56) before endovascular repair versus 47.0 +/- 1.7 (range, 46-49) after (P = not significant). There was a significant increase in the number of suprarenal AAA repairs per year by vascular fellows, 10.0 +/- 1.0 (range, 9-11) before endovascular repair compared with 19.0 +/- 6.5 (range, 13-26) after (P <.05). There was no change in the number of thoracoabdominal aneurysm repairs per year between the two groups, 8.0 +/- 3.0 (range, 4-11) before endovascular repair compared with 7.6 +/- 2.3 (range, 5-9) after.Introduction of an endovascular aneurysm stent-graft program significantly increased the total number of aneurysms treated. Although the number of open aneurysm repairs has remained the same, the complexity of the open aneurysm experience has increased significantly for vascular fellows in training.

  View details for DOI 10.1067/mva.2001.118816

  View details for Web of Science ID 000172305700035

  View details for PubMedID 11700491

• Pathogenesis of abdominal aortic aneurysms: A multidisciplinary research program supported by the National Heart, Lung, and Blood Institute JOURNAL OF VASCULAR SURGERY Wassef, M., Baxter, B. T., Chisholm, R. L., Dalman, R. L., Fillinger, M. F., Heinecke, J., Humphrey, J. D., Kuivaniemi, H., Parks, W. C., Pearce, W. H., Platsoucas, C. D., Sukhova, G. K., Thompson, R. W., Tilson, M. D., Zarins, C. K. 2001; 34 (4): 730-738

  View details for DOI 10.1067/mva.2001.116966

  View details for Web of Science ID 000172020400026

  View details for PubMedID 11668331

• Duplex surveillance of abdominal aortic stent grafts. Seminars in vascular surgery Johnson, B. L., Dalman, R. L. 2001; 14 (3): 227-232

  Abstract

  Aortic stent grafting is gaining acceptance rapidly as a durable and effective alternative to open surgery for abdominal aortic aneurysms (AAA). Unlike follow-up after open surgical procedures, postplacement surveillance protocols are necessary to ensure long-term freedom from device failure or aneurysm rupture. Surveillance protocols incorporating duplex scanning are effective and may reduce overall postplacement expenses. Specific device or patient anatomic features may be prone to failure, and familiarity with each approved device is a prerequisite to the performance of effective device surveillance studies. Mechanisms of failure of aneurysm exclusion after device placement, or "endoleak," have been described and categorized. Endoleak significance is directly related to location, duration, and influence on AAA diameter. Endoleak type also determines when and whether additional interventions are indicated. Future progress in endovascular AAA exclusion will depend in large part on the reliability and utility of cost-effective postprocedure surveillance protocols incorporating duplex ultrasound imaging.

  View details for PubMedID 11561285

• Spontaneous late carotid-cutaneous fistula following radical neck dissection: a case report. Vascular surgery Rodriguez, F., Carmeci, C., Dalman, R. L., Lee, W. A. 2001; 35 (5): 409-413

  Abstract

  The authors present an unusual case of a spontaneous carotid-cutaneous fistula occurring as a late complication 4 years after radical neck dissection and postoperative radiation therapy for tonsillar squamous cell carcinoma in a 50-year-old patient. The etiologic factors predisposing patients to carotid artery rupture following radical neck dissection and a surgical option for carotid artery reconstruction instead of ligation are discussed.

  View details for PubMedID 11565047

• Alpha-tocopherol limits experimental aortic aneurysm enlargement YEH, C. C., Nakahashi, T., Hoshina, K., Xu, C. P., Tsao, P., Karwowski, J. K., Dalman, R. L. LIPPINCOTT WILLIAMS & WILKINS. 2001: 638–38

  View details for Web of Science ID 000168258100030

• Will endovascular repair replace open surgery for abdominal aortic aneurysm repair? 120th Annual Meeting of the American-Surgical-Association Zarins, C. K., Wolf, Y. G., Lee, W. A., Hill, B. B., Olcott, C., Harris, E. J., Dalman, R. L., Fogarty, T. J. LIPPINCOTT WILLIAMS & WILKINS. 2000: 501–5

  Abstract

  To evaluate of the impact of endovascular aneurysm repair on the rate of open surgical repair and on the overall treatment of abdominal aortic aneurysms (AAAs).All patients with AAA who were treated during two consecutive 40-month periods were reviewed. During the first period, only open surgical repair was performed; during the subsequent 40 months, endovascular repair and open surgical repair were treatment options.A total of 727 patients with AAA were treated during the entire period. During the initial 40 months, 268 patients were treated with open surgical repair, including 216 infrarenal (81%), 43 complex (16%), and 9 ruptured (3%) aortic aneurysms. During the subsequent 40 months, 459 patients with AAA were treated (71% increase). There was no significant change in the number of patients undergoing open surgical repair and no significant difference in the rate of infrarenal (238 [77%]) and complex (51 [16%]) repairs. A total of 353 patients were referred for endovascular repair. Of these, 190 (54%) were considered candidates for endovascular repair based on computed tomography or arteriographic morphologic criteria. Analyzing a subgroup of 123 patients, the most common primary reasons for ineligibility for endovascular repair were related to morphology of the neck in 80 patients (65%) and of the iliac arteries in 35 patients (28%). A total of 149 patients underwent endovascular repair. Of these, the procedure was successful in 147 (99%), and 2 (1%) patients underwent surgical conversion. The hospital death rate was 0%, and the 30-day death rate was 1%. During a follow-up period of 1 to 39 months (mean 12 +/- 9), 21 secondary procedures to treat endoleak (20) or to maintain graft limb patency (1) were performed in 17 patients (11%). There were no aneurysm ruptures or aneurysm-related deaths.Endovascular repair appears to have augmented treatment options rather than replaced open surgical repair for patients with AAA. Patients who previously were not candidates for repair because of medical comorbidity may now be safely treated with endovascular repair.

  View details for Web of Science ID 000089602400009

  View details for PubMedID 10998648

• Endovascular repair of abdominal aortic aneurysms: Eligibility rate and impact on the rate of open repair JOURNAL OF VASCULAR SURGERY Wolf, Y. G., Fogarty, T. J., Olcott, C., Hill, B. B., Harris, E. J., Mitchell, R. S., Miller, D. C., Dalman, R. L., Zarins, C. K. 2000; 32 (3): 519-523

  Abstract

  The purpose of this study was to determine the rate of eligibility among patients with abdominal aortic aneurysms (AAAs) considered for endovascular repair and to examine the effect of an endovascular program on the institutional pattern of AAA repair.All patients evaluated for endovascular AAA repair since the inception of an endovascular program were reviewed for determination of eligibility rates and eventual treatment. Open AAA repairs were categorized as simple (uncomplicated infrarenal), complex (juxtarenal, suprarenal, thoracoabdominal, infected), or ruptured, and their rates before and after initiation of an endovascular program were compared.Over 3 years, 324 patients were considered for endovascular AAA repair; 176 (54%) were candidates, 138 (43%) were not candidates, and 10 (3%) did not complete the evaluation. The rate of eligibility increased significantly from 45% (66/148 patients) during the first half of this period to 63% (110/176 patients) during the second half (P <. 001). Candidates were significantly younger (74.4 +/- 7.6 years) than noncandidates (78.3 +/- 6.7 years) (P <.01), and their aneurysm diameter tended to be smaller (57.6 +/- 9.2 mm compared with 60.8 +/- 12.3 mm; P =.06). The most common reason for ineligibility was an inadequate proximal aortic neck. Of 176 candidates, 78% underwent endovascular repair, and 6% underwent open repair. Of 138 noncandidates, 56% underwent surgical repair. Over a period of 6 years, 542 patients with AAAs (429 simple, 86 complex, 27 ruptured) underwent open repair. The total number and ratio of simple to complex open repairs for nonruptured aneurysms during the 3 years before the initiation of the endovascular program (213 simple, 44 complex) were not significantly different from the repairs over the subsequent 3-year period (216 simple, 42 complex). Similarly, no difference in the total number and the ratio of simple to complex open repairs was found between the first and the second 18-month periods since the initiation of the endovascular program.The rate of eligibility of patients with AAA for endovascular repair appears to be higher than previously reported. The presence of an active endovascular program has not decreased the number or shifted the distribution of open AAA repair.

  View details for Web of Science ID 000089230100023

  View details for PubMedID 10957658

• Open saphenectomy complications following lower extremity revascularization CARDIOVASCULAR SURGERY Dalman, R. L., Abbruzzese, T., Bushnik, T., Harris, E. J. 2000; 8 (1): 51-57

  Abstract

  A review of saphenectomy site complications following lower extremity revascularization was conducted. Leg incisions used for 133 consecutive infrainguinal bypass procedures were categorized by location. Patient and procedural risk factors were analyzed for risk of wound complications. Procedure, limb and patient outcome were reported via life table analysis. Incisional wound complications followed 32/133 procedures (24%), including 15 groin, eight saphenectomy, five distal and four vein/distal incisions. There were five grade I and three grade II saphenectomy complications. Only weight (body mass index) predicted the likelihood of wound complication (P < 0.05). The 6-month primary patency rate was 79% (mean follow-up 22 months). Four-year assisted primary patency, limb salvage and survival rates were 75, 87 and 57%, respectively. Most bypass-related wound complications (24/32, 75%) involve arterial access incisions. Incisional complications are related to body mass index. Only 6% of GS vein bypass procedures develop saphenectomy site complications. Limiting saphenectomy size may not significantly reduce incisional morbidity following bypass grafting.

  View details for Web of Science ID 000084649000008

  View details for PubMedID 10661704

• Dose-dependent limitation of arterial enlargement by the matrix metalloproteinase inhibitor RS-113,456 Annual Meeting of the Association-for-Academic-Surgery Karwowski, J. K., Markezich, A., Whitson, J., Abbruzzese, T. A., Zarins, C. K., Dalman, R. L. ACADEMIC PRESS INC ELSEVIER SCIENCE. 1999: 122–29

  Abstract

  Arterial diameter changes in response to flow. Chronic flow-mediated arterial enlargement may be mediated through metalloproteinase activity in the extracellular matrix of the arterial wall. We examined flow-mediated enlargement in the setting of increasing competitive matrix metalloproteinase (MMP) inhibition and with respect to gelatinase A and B expression and activity.Left common femoral arteriovenous fistulas (AVFs) were created in dose-response (52) and time course (34) cohorts of rats. Dose-response rats received either vehicle alone or 12.5, 25, or 37. 5 mg/kg b.i.d. RS 113,456, a competitive MMP inhibitor. Heart rate, blood pressure, and weight were measured at intervals following AVF construction. Aortic and common iliac diameters were measured on postoperative day (POD) 21. Untreated time course rats were sacrificed on PODs 0 (no AVF), 3, 7, 14, and 21. Aortic diameter was measured and the vessels were harvested for tissue analysis. Equal amounts of aortic RNA underwent reverse transcription and polymerase chain reaction with primers for MMP-2, MMP-9, and GAPDH. Zymography was performed on iliac artery tissue to measure gelatinolytic activity.A significant, stepwise reduction in flow-mediated aortic and left common iliac enlargement following left femoral AVF creation was noted with progressively higher doses of RS 113,456 without apparent hemodynamic or toxic effects. Right common iliac diameter was unchanged. Over 21 days following AVF creation, there was an upward trend in expression and activity for MMP-2 not evident for MMP-9.Flow-mediated arterial enlargement is limited by competitive MMP inhibition in a dose-dependent fashion. MMP-dependent flow-mediated enlargement may involve differential expression and activity of MMP-2 and MMP-9.

  View details for Web of Science ID 000083644800017

  View details for PubMedID 10527713

• Modular systems in the treatment of abdominal aortic aneurysms: lessons learned in the development of designer endografts. Seminars in vascular surgery Harris, E. J. 1999; 12 (3): 170-175

  Abstract

  Treatment of abdominal aortic aneurysms with endoluminal stent-grafts is gaining increased interest. Since the original home-made stent-graft was developed in 1991, a multitude of devices have been developed for this treatment. Modular endografts have evolved during this time and offer several significant advantages. Thorough preoperative imaging and assessment is critical to the success of this new therapy for abdominal aortic aneurysms. Lessons learned during the development of the Medtronic AneuRx endograft and its early clinical trials are discussed.

  View details for PubMedID 10498259

• In vivo flow-independent T2 measurements of superior mesenteric vein blood in diagnosis of chronic mesenteric ischemia: A preliminary evaluation ACADEMIC RADIOLOGY Li, K. C., Dalman, R. L., Wright, G. A. 1999; 6 (9): 530-534

  Abstract

  The authors attempted to determine whether the T2 relaxation time of superior mesenteric vein (SMV) blood would decrease in patients with chronic mesenteric ischemia after a meal.Thirty-two patients without chronic mesenteric ischemia and eight patients with symptomatic chronic mesenteric ischemia underwent magnetic resonance (MR) imaging. All examinations were performed with a 1.5-T unit, a modified Carr-Purcell-Meiboom-Gill sequence, final section-selective pulse of 180 degrees, and spiral readout gradients. Measurements of SMV blood T2 were obtained after at least 6 hours of fasting and 15 and 35 minutes after ingestion of 240 mL of a liquid nutritional supplement. Maximal change of the SMV blood T2 was expressed as a percentage of the fasting T2 in all patients.In control patients, SMV blood T2 increased postprandially by 9.4% +/- 1.3 (95% confidence level; range, 6.8%-11.9%) (data range, -7.3% to 25.6%) compared with fasting T2. In symptomatic patients, SMV blood T2 decreased postprandially by 15.8% +/- 2.2 (95% confidence level; range, -20.1% to -10.7%) (data range, -7.9% to -25.3%). The difference between the two groups was statistically significant (P < .0001 by Student unpaired t test).Measurement of SMV blood T2 is a promising test for chronic mesenteric ischemia diagnosis. Therefore, conversion of T2 measurements to estimate oxygen saturation may not be necessary for all cases of this clinical indication.

  View details for Web of Science ID 000086033600004

  View details for PubMedID 10894061

• Reoperation for carotid stenosis is as safe as primary carotid endarterectomy 13th Annual Meeting of the Western-Vascular-Society Hill, B. B., Olcott, C., Dalman, R. L., Harris, J., Zarins, C. K. MOSBY-ELSEVIER. 1999: 26–34

  Abstract

  Patients with recurrent carotid artery stenosis are sometimes referred for carotid angioplasty and stenting because of reports that carotid reoperation has a higher complication rate than primary carotid endarterectomy. The purpose of this study was to determine whether a difference exists between outcomes of primary carotid endarterectomy and reoperative carotid surgery.Medical records were reviewed for all carotid operations performed from September 1993 through March 1998 by vascular surgery faculty at a single academic center. The results of primary carotid endarterectomy and operation for recurrent carotid stenosis were compared.A total of 390 operations were performed on 352 patients. Indications for primary carotid endarterectomy (n = 350) were asymptomatic high-grade stenosis in 42% of the cases, amaurosis fugax and transient ischemic symptoms in 35%, global symptoms in 14%, and previous stroke in 9%. Indications for reoperative carotid surgery (n = 40) were symptomatic recurrent lesions in 50% of the cases and progressive high-grade asymptomatic stenoses in 50%. The results of primary carotid endarterectomy were no postoperative deaths, an overall stroke rate of 1.1% (three postoperative strokes, one preoperative stroke after angiography), and no permanent cranial nerve deficits. The results of operations for recurrent carotid stenosis were no postoperative deaths, no postoperative strokes, and no permanent cranial nerve deficits. In the primary carotid endarterectomy group, the mean hospital length of stay was 2.6 +/- 1. 1 days and the mean hospital cost was $9700. In the reoperative group, the mean length of stay was 2.6 +/- 1.5 days and the mean cost was $13,700. The higher cost of redo surgery is accounted for by a higher preoperative cerebral angiography rate (90%) in redo cases as compared with primary endarterectomy (40%).In this series of 390 carotid operations, the procedure-related stroke/death rate was 0.8%. There were no differences between the stroke-death rates after primary carotid endarterectomy and operation for recurrent carotid stenosis. Operation for recurrent carotid stenosis is as safe and effective as primary carotid endarterectomy and should continue to be standard treatment.

  View details for Web of Science ID 000081410700007

  View details for PubMedID 10394151

• Aortic aneurysmorrhaphy: Establishing concurrent results for comparison with endoluminal therapies VASCULAR SURGERY Harris, E. J., Dalman, R. L. 1998; 32 (6): 595-602

  View details for Web of Science ID 000076946200010

• Matrix metalloproteinase inhibition limits arterial enlargement in a rodent arteriovenous fistula model 59th Annual Meeting of the Society-of-University-Surgeons Abbruzzese, T. A., Guzman, R. J., MARTIN, R. L., Yee, C., Zarins, C. K., Dalman, R. L. MOSBY-ELSEVIER. 1998: 328–34

  Abstract

  We administered a specific, nonselective matrix metalloproteinase (MMP) inhibitor (RS-113,456) to examine the effect of MMP inhibition on flow-mediated arterial enlargement in a rodent arteriovenous fistula (AVF) model.Four groups of male Sprague-Dawley rats were created: sham (sham operated; n = 10), control (2.0 mm left common femoral AVF alone; n = 16), vehicle (AVF plus 0.5 mL vehicle orally twice a day; n = 20), and treatment (AVF plus 25 mg/kg RS-113,456 in 0.5 mL vehicle orally twice a day; n = 16). Heart rate, mean arterial pressure, and body weight were recorded on postoperative days 0, 7, 14, and 21. On day 21, AVF patency was confirmed, the infrarenal aorta and common iliac arteries were exposed, blood flow velocity and external diameter were measured, and wall shear stress (WSS) was calculated. Analysis was performed by paired, two-tailed Student t test, one-way analysis of variance, and the Bonferroni/Dunn procedure for post hoc testing.Heat rate, mean arterial pressure, and weight did not vary at any time between groups. Aortic and left iliac diameter was larger in the AVF groups than in sham groups (P < .001), and control and vehicle groups were larger than treatment groups (P < .0001). Changes in aortic and left iliac flow were also significant (AVF was more than sham and control, and vehicle was more than treatment). No difference in aortic and left iliac artery velocity and WSS or right iliac diameter, velocity, flow, or WSS was observed between groups.MMP inhibition diminishes flow-mediated arterial enlargement in the rat AVF model.

  View details for Web of Science ID 000075252200054

  View details for PubMedID 9706156

• Limb salvage surgery in spinal cord injury patients 11th Annual Meeting of the Western-Vascular-Society Dalman, R. L., Harris, E. J., Walker, M. T., Perkash, I. ELSEVIER SCIENCE INC. 1998: 60–64

  Abstract

  Advances in the care and rehabilitation of patients with spinal cord injuries (SCI) have resulted in extended survival following injury. Increasingly, we are faced with difficult chronic lower extremity ischemic complications in SCI patients. Recognizing limitations associated with amputation in these nonambulatory patients, we report the preliminary results of a program of selective limb salvage via arterial reconstructive surgery. Retrospective chart review was performed on the records of the Veterans Affairs Palo Alto Health Care System SCI unit. Since 1989, 15 revascularization procedures were identified in 10 SCI patients. All patients suffered from ischemic ulceration and/or gangrene. Procedures performed included femorotibial bypass (8), aortofemoral bypass (4), femoro-femoral bypass (2), and axillobifemoral bypass (AXF) (1). All patients were men. The mean age was 56 (range 43-73). Follow-up was available on 10 procedures performed in seven patients since 1992. Mean follow-up was 17 months. One patient died 3 months following distal bypass. The AXF occluded within 1 month. One distal bypass occluded in the immediate postoperative period and could not be salvaged. All other grafts remain patent, and all wounds have healed following successful bypass. One patient developed pressure ulceration following AXF grafting due to postoperative upper extremity limitations. No other complications were encountered. Standard arterial reconstructive procedures can be performed safely and successfully in SCI patients, despite diminished limb blood flow due to inactivity, and atrophic arteries, muscle, and fascia. Axillobifemoral bypass grafting may not be suitable in SCI due to requirements for upper extremity-based mobility. Confirmation of benefit of limb salvage versus amputation awaits comparison between patients eligible for either procedure.

  View details for Web of Science ID 000071300900010

  View details for PubMedID 9451998

• Upper extremity revascularization proximal to the wrist ANNALS OF VASCULAR SURGERY Dalman, R. L., Olcott, C. 1997; 11 (6): 643-650

  View details for Web of Science ID A1997YD48200016

  View details for PubMedID 9363314

• Chronic mesenteric ischemia: Use of in vivo MR imaging measurements of blood oxygen saturation in the superior mesenteric vein for diagnosis RADIOLOGY Li, K. C., Dalman, R. L., Chen, I. Y., Pelc, I. R., SONG, C. K., Moon, W. K., Kang, M. I., Wright, G. A. 1997; 204 (1): 71-77

  Abstract

  To determine if dogs and humans with chronic mesenteric ischemia demonstrate a decrease in the percentage of oxygenated hemoglobin (%HbO2) in the superior mesenteric vein (SMV) after a meal.In 10 dogs, ameroid rings were surgically implanted around the superior mesenteric arteries to create gradual stenosis. Pre- and postoperative angiograms and pre- and postprandial magnetic resonance (MR) oximetry measurements of the SMV %HbO2, with flow-independent T2 measurements of venous blood, were obtained at different times. In 10 patients with atherosclerotic disease and six patients with symptomatic chronic mesenteric ischemia, the same measurements were obtained after at least 6 hours of fasting and at 15, 35, and 45 minutes after ingestion of a liquid nutritional supplement.In seven dogs, the postprandial SMV %HbO2 increased an average of 2.5% +/- 0.8 before surgery and decreased an average of 6.3% +/- 2.1 when hemodynamically significant (>70%) stenosis of the superior mesenteric artery developed 7-14 days after surgery. In the 10 patients without ischemia, the SMV %HbO2 increased by 4.6% +/- 0.6, whereas in the symptomatic patients a postprandial decrease of 8.8% +/- 0.7 occurred (P < .0001).Measurement of the SMV %HbO2 with MR oximetry is a promising test for diagnosis of chronic mesenteric ischemia.

  View details for Web of Science ID A1997XF19400016

  View details for PubMedID 9205225

• Subclavian vein thrombosis: Outcome analysis based on etiology and modality of treatment 8th Annual Meeting of the American-Venous-Forum Beygui, R. E., Olcott, C., Dalman, R. L. SPRINGER VERLAG. 1997: 247–55

  Abstract

  Therapeutic options for subclavian vein thrombosis (SVT) include anticoagulation, thrombolysis, endovascular repair, and direct surgical intervention. The most effective method of treatment remains undetermined. We reviewed our institutional experience over 7 years with SVT patients to compare the results of treatment based on etiology of thrombosis. Nineteen patients suffered SVT secondary to malignancy, catheter placement, radiation, or hypercoagulability. Thirteen were Paget-Schroetter (PSS), or primary effort-related SVT. Patients with dialysis access procedures were excluded. Thrombolysis was initiated in 31/32 patients. Success was defined as complete obliteration of clot. Adjunctive treatment to relieve external compression or improve lumenal contour was performed on 16/32 patients (eight PSS, eight secondary SVT). Success of adjunctive treatment was defined as return to baseline activity without symptoms. Objective follow up (venography or duplex scanning) was included when available. Adjunctive treatment included balloon angioplasty (6), stent placement (5), first rib resection and scalenectomy (4), and vein reconstruction (4). Initial treatment success with thrombolysis was achieved in 26/31 patients (84%). Angioplasty failed in three PSS and three secondary SVT patients. Stent placement was successful in 2/5 patients (both secondary SVT). Surgery was performed only on PSS patients: first rib resection and scalenectomy succeeded 4/4 times, vein reconstruction 2/4. Twenty-eight patients were given long-term therapy with oral anticoagulation with good long-term results. Seven patients experienced complications, including one death. Results of SVT therapy including thrombolysis and oral anticoagulation are very good. Angioplasty and stent placement in secondary SVT patients appears to add little long term benefit. Surgery may improve outcome in selected PSS patients, although the additional benefit could not be determined by the design of this study. Evaluation and treatment limited only to PSS excludes the majority of SVT patients.

  View details for Web of Science ID A1997WW54300006

  View details for PubMedID 9140599

• Matrix metalloproteinase inhibition decreases flow mediated arterial enlargement Circulation (suppl) Abbruzzese TA, Guzman RL, Martin RL, Zarins CK, Dalman RL 1997; 96: I-172
• In vivo magnetic resonance evaluation of blood oxygen saturation in the superior mesenteric vein as a measure of the degree of acute flow reduction in the superior mesenteric artery: Findings in a canine model ACADEMIC RADIOLOGY Li, K. C., Pelc, L. R., Dalman, R. L., Wright, G. A., HOLLETT, M. D., Chen, I., SONG, C. K., Porath, T. S. 1997; 4 (1): 21-25

  Abstract

  The authors tested the hypothesis that changes in oxygen saturation (%HbO2) in the superior mesenteric vein (SMV), as measured with in vivo magnetic resonance (MR) oximetry, correlate with the degree of acute superior mesenteric artery (SMA) flow reduction.Ten mongrel dogs were studied. A catheter was inserted into the SMV, and a perivascular ultrasonic flow probe and an adjustable mechanical occluder were placed around the SMA. MR oximetry was carried out at the resting state and after the SMA was constricted to predetermined levels (0%-75% of initial flow). In seven dogs, SMV blood samples were obtained immediately before and after each MR measurement; %HbO2 was measured simultaneously by using an oximeter. With linear regression analysis, the SMV %HbO2 measurements obtained at MR imaging were compared with those obtained at oximetry. With a logistic model, MR imaging changes in SMV %HbO2 were compared with the degree of SMA flow reduction.SMV %HbO2 measurements obtained with MR imaging correlated well with those obtained with oximetry (r = .97). Changes in SMV %HbO2 measured at MR imaging also correlated well with the degree of SMA flow reduction, as determined with a logistic model (P = .01).Noninvasive in vivo MR measurements of SMV %HbO2 can be used to determine the degree of acute SMA flow reduction with a high degree of accuracy in a canine model.

  View details for Web of Science ID A1997WF65900004

  View details for PubMedID 9040866

• Diminished postprandial hyperemia in patients with aortic and mesenteric arterial occlusive disease. Quantification by magnetic resonance flow imaging. Circulation Dalman, R. L., Li, K. C., Moon, W. K., Chen, I., Zarins, C. K. 1996; 94 (9): II206-10

  Abstract

  Superior mesenteric blood flow in the fasting and postprandial state in humans can be measured accurately by cine phase-contrast (CPC) magnetic resonance (MR) imaging. Postprandial flow changes associated with mesenteric arterial occlusive disease (MAOD) are unknown.We used CPC MR imaging to measure fasting and postprandial blood flow in the superior mesenteric artery (SMA) and vein (SMV) in 22 patients (mean age, 69 years) with aortic occlusive disease and MAOD and compared the results with similar measurements in 8 younger, asymptomatic volunteers (mean age, 34 years). All 22 patients had stenosis or occlusion of the splanchnic or pelvic arteries demonstrated by contrast aortography; 19 were asymptomatic and 3 had symptoms of chronic mesenteric ischemia. Mean fasting blood flow was higher in patients (4.5 mL.kg-1.min-1) than in volunteers (2.3 mL.kg-1.min-1; P < .01). However, postprandial hyperemia (mean percentage change in SMV blood flow) was less in the asymptomatic (70%; P < .001) and symptomatic patients (29%; P < .01) than in the volunteers. Postprandial SMV flow was similar to SMA flow in the patients but was significantly greater than SMA flow in the volunteers (P < .005).Postprandial mesenteric hyperemia is reduced in older patients with MAOD. The role of aging alone has not been determined. Fasting and postprandial flow changes in these patients may predict the onset of chronic mesenteric ischemia.

  View details for PubMedID 8901747

• Diminished postprandial hyperemia in patients with aortic and mesenteric arterial occlusive disease - Quantification by magnetic resonance flow imaging CIRCULATION Dalman, R. L., Li, K. C., Moon, W. K., Chen, I., Zarins, C. K. 1996; 94 (9): 206-210

  View details for Web of Science ID A1996VP69000038

• Is completion arteriography mandatory after reversed-vein bypass grafting? JOURNAL OF VASCULAR SURGERY Dalman, R. L., Harris, E. J., Zarins, C. K. 1996; 23 (4): 637-644

  Abstract

  Many surgeons advocate uniform performance of operative completion arteriography after leg bypass surgery to ensure technical success and to optimize short- and intermediate-term graft patency. To determine the impact of this practice on the outcome of reversed-vein bypass surgery and associated patient charges, we reviewed our series of consecutive nonemergent leg bypass procedures. Ninety-three infrainguinal bypass procedures were performed in 80 patients (76 men and 4 women) from September 1991 to August 1994. The patients' average age was 67 years (range, 30 to 92 years). Follow-up (mean, 113.1 months; range, 1 to 36 months) was available on 91 grafts (97%). Indications for surgery included limb salvage in 75 cases, claudication in 12 cases, and popliteal aneurysm exclusion in 6 cases. All patients survived surgery. Primary graft patency rates as determined by life-table analysis were 87%, 81%, 78%, and 78% at 6 months and at 1, 2, and 3 years, respectively. Limb-salvage rates were 95%, 91%, 87% and 87% at the same intervals. Bypass procedures were divided into two groups. The 25 grafts in group 1 were evaluated with inspection, continuous-wave Doppler insonation, and routine completion arteriography. The 68 grafts in group 2 were evaluated by inspection and insonation alone. Fourteen grafts occluded after surgery (average, 5 months; range, 1 to 12 months), five in group 1 and nine in group 2. The likelihood of graft occlusion was similar in both groups (p = 0.42). The optimal method of confirming technical adequacy after bypass surgery in the clinically satisfactory graft remains uncertain. Charges for completion arteriography at our institution average $700, including 15 minutes of additional operative time. In our experience, these charges do not appear to be justified by improved short- or intermediate-term graft patency rates in reversed-vein grafts when completion arteriography is performed.

  View details for Web of Science ID A1996UJ12600016

  View details for PubMedID 8627900

• SIMULTANEOUS MEASUREMENT OF FLOW IN THE SUPERIOR MESENTERIC VEIN AND ARTERY WITH CINE PHASE-CONTRAST MR-IMAGING - VALUE IN DIAGNOSIS OF CHRONIC MESENTERIC ISCHEMIA - WORK-IN-PROGRESS RADIOLOGY Li, K. C., Hopkins, K. L., Dalman, R. L., SONG, C. K. 1995; 194 (2): 327-330

  Abstract

  To evaluate the use of measurements of blood flow in the superior mesenteric vein (SMV) and superior mesenteric artery (SMA) simultaneously acquired with phase-contrast cine magnetic resonance (MR) imaging for diagnosing chronic mesenteric ischemia.Simultaneous measurements of flow in the SMV and SMA were obtained in six healthy volunteers and eight patients with angiographically proved SMA stenosis (six asymptomatic, two symptomatic). Flow dynamics in both vessels were correlated with the degree of arterial disease seen at angiography and with the presence or absence of ischemic symptoms.Postprandial SMV and SMA flow increased substantially less in patients with atherosclerosis than in volunteers. Comparison of simultaneous SMV and SMA flow measurements provided more information about collateral flow to and from the mesenteric circulation than did either the SMV or SMA flow measurement alone.Simultaneous SMV and SMA flow measurement with cine phase-contrast MR imaging may be useful in diagnosing and understanding chronic mesenteric ischemia.

  View details for Web of Science ID A1995QC67800009

  View details for PubMedID 7824706

• OXYGEN-SATURATION OF BLOOD IN THE SUPERIOR MESENTERIC VEIN - IN-VIVO VERIFICATION OF MR-IMAGING MEASUREMENTS IN A CANINE MODEL - WORK-IN-PROGRESS 1993 RSNA Scientific Assembly Li, K. C., Wright, G. A., Pelc, L. R., Dalman, R. L., Brittain, J. H., WEGMUELLER, H., Lin, D. T., SONG, C. K. RADIOLOGICAL SOC NORTH AMER. 1995: 321–25

  Abstract

  To evaluate the accuracy of magnetic resonance (MR) imaging in estimating oxygen saturation of blood (%HbO2) in the superior mesenteric vein (SMV) of a canine model in vivo.MR imaging was used to measure the T2 of blood in samples obtained via a catheter placed in the SMV in seven mongrel dogs. %HbO2 was measured with a reflectance oximeter. These measurements were obtained at the resting state, during superior mesenteric artery occlusion, and after reperfusion. MR imaging and oximeter measurements were then compared by using linear regression analysis.Refocusing intervals (tau 180) of 12 and 24 msec were used for 17 and 18 %HbO2 measurements with MR imaging, respectively. With tau 180 of 12 msec, there was an excellent correlation between MR imaging measurements and oximeter measurements (r = .969). The intercept was 5.3% and the slope was 0.959. With tau 180 of 24 msec, r = .953, the intercept was 15.4%, and the slope was 0.817.Estimates of %HbO2 in the SMV with MR imaging are accurate in the range of most clinical interest.

  View details for Web of Science ID A1995QC67800008

  View details for PubMedID 7824705

• PHASE-CONTRAST MRI ASSESSMENT OF PEDAL BLOOD-FLOW EUROPEAN RADIOLOGY Debatin, J. F., Dalman, R., Herfkens, R. J., Harris, E. J., Pelc, N. J. 1995; 5 (1): 36-42

  View details for Web of Science ID A1995QK12800007

• ANTIPHOSPHOLIPID ANTIBODIES IN VASCULAR-SURGERY PATIENTS - A CROSS-SECTIONAL STUDY ANNALS OF SURGERY Taylor, L. M., Chitwood, R. W., Dalman, R. L., Sexton, G., Goodnight, S. H., Porter, J. M. 1994; 220 (4): 544-551

  Abstract

  Autoantibodies to phospholipid (aPL) have been associated with vascular thromboses in cerebral, coronary, and peripheral venous and arterial sites. To date, no large cross-sectional study has examined the incidence of occurrence of aPL in patients with peripheral arterial disease.A cross-sectional study was performed with patients admitted for vascular surgery procedures to treat peripheral arterial disease for 23 months between January 1, 1990 and November 1, 1991. Consecutive patients were evaluated for the presence of aPL. Medical records for each patient were reviewed in detail, and historic, operative, and postoperative parameters were tabulated for relationship to the presence of aPL.Two hundred thirty-four patients underwent complete testing for aPL. All patients were receiving chronic aspirin therapy. This represented 86% of admissions. Antiphospholipid antibodies were detected in 60 patients (26%). No differences in age, sex, operation performed, or postoperative outcome were found between patients with and without aPL. However, patients with aPL were 1.8 times more likely to have undergone previous lower extremity (LE) vascular surgery than patients without aPL (95% confidence interval = 1.0 - 3.6, p = 0.047). Patients with aPL and previous LE vascular surgery were 5.6 times more likely to have had occlusion of that procedure than patients without aPL (95% confidence interval = 1.9 - 16.8, p = 0.03). The occluded previous LE procedures had a shorter duration of patency before occlusion in patients with aPL than in those without (mean duration of patency 17 months vs. 50 months, p < 0.003). Patients with occluded previous LE procedures and aPL were 4 times more likely to be female (95% C.I. = 1.4 - 11.3, p = 0.018).The incidence of aPL in vascular surgery patients is substantial. Vascular surgery patients with aPL are more likely to have failure of previous LE bypass procedures and to be female and the bypass failure occurs significantly more rapidly than in patients without aPL. Based on these data, testing of vascular surgery patients for aPL and investigation of alternative antithrombotic treatment regimens in patients with aPL appears warranted.

  View details for Web of Science ID A1994PL39300012

  View details for PubMedID 7944664

• BASE-LINE SILENT CEREBRAL INFARCTION IN THE ASYMPTOMATIC CAROTID ATHEROSCLEROSIS STUDY STROKE Brott, T., Tomsick, T., Feinberg, W., Johnson, C., Biller, J., Broderick, J., Kelly, M., Frey, J., Schwartz, S., Blum, C., Nelson, J. J., Chambless, L., Toole, J., Seeger, J., Bruck, D., VOLD, B., Laguna, J., CHESSER, M., Archer, L., NICKOLS, J. R., MacDonald, C., Hodak, J., Flom, R., HUNSLEY, S., Jahnke, H., Lefkowitz, D., Satterfield, J., Cohen, S., Jacobs, B., Holgate, R., JOABOUR, B., Walden, K., VESCERA, C., Bernstein, R., RADOSEVICH, P., McCormick, P., Elias, L., Furlan, A., BRYERTON, B., Sauerbeck, S., Mohr, J. P., Petty, G., Libman, R., Marshall, R., Cruz, A., Gonzalez, T., Cabrera, A., EARLY, C., Stone, B., Maguire, M. P., Schecter, J., Capps, R., Glass, J., Farrar, N., Patel, S., WILCZEWSKI, J., Robertson, W., Daley, S., JANESKY, C., Meilstrup, J., Friedman, D., Smith, F., Bedard, F., Adams, H., Love, B., Bendixen, B., Vining, L., KARBOSKI, D., GRIMSMAN, K., Lee, C., Young, B., Pettigrew, C., Dempsey, R., Sadler, R., Rice, L., Diana, L., Norton, A., Lin, Z. S., LANGENECKER, J., Jenny, D., Gupta, S., Burke, K., Warner, J., LOBNER, S., Taylor, J., Cockrell, A., Conway, C., Smith, R., Brown, R., Weisbrot, F., Kamin, S., Back, T., Rogers, C., Bruno, A., JOHNSON, E., Steel, S., Yao, J., Chadwick, L., Hughes, R., LEPLER, B., Lang, V., Benoit, C., CAHANIN, V., Taylor, L., Coull, B., Whitaker, L., Dalman, R., Bivins, D., Foley, C., Green, R., Cohen, D., McNamara, J., Levine, R., Hurley, J., Wilcox, M., Blackburn, C., MESTAYER, R., Almond, C., Clagett, G. P., Unwin, H., Bryan, W., MATKINS, C., Cooper, P., Rowed, D., Bowyer, B., Robertson, J., Vasu, K., Acker, J., Bradley, A., Riley, J., Connell, J., GIAMPAPA, M. A., TAYLOR, C., Stahl, N., Thomas, T., Bennett, S., Fox, A., Mayer, C., White, C., Assis, L., Pexman, W., Paddock, L., Crane, R., Harris, S., BUTTERLEVY, K., Brass, L., Fayad, P., Sumpio, B., Lovejoy, A., Kisiel, D., Toole, J. F., Howard, V. J., Purvis, S., Vernon, D. D., Needham, K., Beck, P., Dozier, M., Howard, G., ESSICK, K., Chambless, L. E., Bland, E., Locklear, J. 1994; 25 (6): 1122-1129

  Abstract

  In a group of patients with high-grade asymptomatic carotid artery stenosis, we prospectively determined the prevalence and radiological characteristics of clinically asymptomatic brain infarction evident on computed tomography. Risk factors and extent of carotid disease were also determined.Patients randomized into the Asymptomatic Carotid Atherosclerosis Study (ACAS) underwent a neurological history, a detailed stroke/transient ischemic attack questionnaire, and a detailed neurological examination. Computed tomography scans were examined by standardized criteria developed as part of a quality-control program supervised by a neuroradiologist. The presence, location, and size of all cerebral infarctions evident by computed tomography were determined.Among 1132 patients, 848 had no history of stroke or transient ischemic attack. One hundred twenty-six patients (15%) had a silent infarct; 95 (11%) had one, 24 (3%) had two, and 7 (1%) had three or more infarcts. The infarct size was small and deep for 117 patients (72%), less than one-half lobe for 45 (28%), and one-half to less than one lobe for 1 (0.5%). The silent infarcts were evenly distributed ipsilaterally and contralaterally to the study artery but were significantly more frequent in the right hemisphere (P < .05). Factors associated with silent infarction were abnormal gait (P < .001), abnormal deep tendon reflexes or plantar responses (P = .038), but not degree of carotid stenosis. Silent infarction was less frequent among this totally asymptomatic cohort (15%) compared with those with transient ischemic attacks (34/139, 25%; P < .001).Silent infarction in the setting of asymptomatic carotid stenosis is not uncommon, but silent infarctions are rarely sizable. The clinical significance of silent cerebral infarction in patients with asymptomatic carotid artery stenosis has yet to be established.

  View details for Web of Science ID A1994NP14200006

  View details for PubMedID 8202968

• Genetic and metabolic causes of arterial disease. Annals of vascular surgery Fann, J. I., Dalman, R. L., Harris, E. J. 1993; 7 (6): 594-604

  View details for PubMedID 8123465

• ENDOTHELIN PRODUCTION BY HYPOXIC HUMAN ENDOTHELIUM JOURNAL OF VASCULAR SURGERY Gertler, J. P., OCASIO, V. H., Dalman, R. L., Porter, J., Paterson, I., Edwards, J., Thompson, M. M. 1993; 18 (2): 178-184

  Abstract

  The physiologic significance of endothelin remains incompletely defined. Procoagulant and antifibrinolytic activities are increased in hypoxic cultured human umbilical venous endothelial cells (HUVEC). We examined the effect of hypoxia on HUVEC endothelin-1 production in vitro to determine whether a correlation existed between the procoagulant and antifibrinolytic response to hypoxia previously observed and an increase in vasoconstrictor peptide secretion by hypoxic HUVEC.Cultured HUVEC were rendered hypoxic (PO2 = 40 mm Hg) or control (PO2 = 120 mm Hg) for 24 hours. Media were either standard, 5 gm glucose/L (high glucose), or contained 500 units superoxide dismutase/ml (SOD). Endothelin-like immunoreactivity for endothelin-1 (ET-IR) in conditioned media was measured by radioimmunoassay and expressed as mean femtomoles per milliliter (+/- SD) per 100,000 cells. Viability of HUVEC was assessed by trypan blue exclusion. Significance was determined by use of Student's t test.Conditioned media from hypoxic cells contained 76% more ET-IR than was found in control counterparts (p < 0.004). The addition of high glucose or SOD did not diminish ET-IR; a trend to higher ET-IR was present in both these groups versus standard media (303% and 226%, respectively, p < 0.03).Thus 24 hours of hypoxia caused an increase in conditioned-media ET-IR in cultured HUVEC. Because SOD or greater substrate availability did not diminish endothelin presence in conditioned media, it seems that hypoxic induction of endothelin-1 production or secretion is signaled in a fashion unrelated to cell toxicity from the hypoxic period.

  View details for Web of Science ID A1993LT17500004

  View details for PubMedID 8350426

• Extra-anatomic bypass. Annals of vascular surgery Fann, J. I., Harris, E. J., Dalman, R. L. 1993; 7 (4): 378-383

  View details for PubMedID 8268081

• Heritable arteriopathy. Seminars in vascular surgery Fann, J. I., Dalman, R. L. 1993; 6 (1): 46-55

  View details for PubMedID 8252228

• UPPER EXTREMITY ARTERIAL BYPASS DISTAL TO THE WRIST 7TH ANNUAL MEETING OF THE WESTERN VASCULAR SOC Nehler, M. R., Dalman, R. L., Harris, E. J., Taylor, L. M., Porter, J. M. MOSBY-YEAR BOOK INC. 1992: 633–42

  Abstract

  Seventeen arterial bypass procedures distal to the wrist have been performed in 13 men and two women at the Oregon Health Sciences University during the past 9 years. Ten patients had traumatic true or false aneurysms of the ulnar artery with digital embolization. Five patients with end-stage renal disease had severe hand and finger ischemia manifested by rest pain or digital ulceration resulting from widespread forearm and hand arterial occlusions. Patients with aneurysms of the ulnar artery underwent excision and reversed autogenous vein grafting (n = 11) from the distal ulnar artery in the forearm to the superficial palmar arch. All the patients with end-stage renal disease had severe occlusive disease of the forearm and hand arteries and underwent a variety of procedures including radial-radial bypass (n = 2), ulnar-ulnar bypass (n = 2), radial-radial bypass with takedown of a Brescia-Cimino fistula (n = 1), and brachial-radial bypass (n = 1). High-quality upper extremity and magnification hand arteriography was essential for operative planning and was available on all patients. Distal saphenous vein from the ankle or foot was the graft source in 16 procedures and basilic vein the source in one procedure. All operations were performed with headlight illumination, optical loupes, fine sutures, and microvascular instruments. There were no operative deaths or major complications. The mean follow-up period was 14 months. Of the 17 grafts, 16 remained patent by clinical and vascular lab criteria. The single occlusion occurred in an ulnar aneurysm bypass and was accompanied only by mild intolerance to cold.(ABSTRACT TRUNCATED AT 250 WORDS)

  View details for Web of Science ID A1992JT81200013

  View details for PubMedID 1404683

• DUPLEX ULTRASOUND CRITERIA FOR DIAGNOSIS OF SPLANCHNIC ARTERY-STENOSIS OR OCCLUSION JOURNAL OF VASCULAR SURGERY Moneta, G. L., Yeager, R. A., Dalman, R., ANTONOVIC, R., Hall, L. D., Porter, J. M. 1991; 14 (4): 511-520

  Abstract

  Mesenteric artery duplex scanning appears promising for detection of splanchnic artery stenosis or occlusion or both in patients with symptoms suggestive of chronic intestinal ischemia. However, no specific duplex criteria have been developed for detection of mesenteric artery stenosis. We obtained mesenteric artery duplex scans and infradiaphragmatic lateral aortograms in 34 patients to determine duplex criteria for mesenteric stenosis. Seventy percent or greater angiographic stenosis was present in 10 superior mesenteric arteries and 16 celiac arteries. Duplex scans were reviewed to determine if celiac artery and superior mesenteric artery ratios of peak systolic velocities and end-diastolic velocities to peak aortic systolic velocity, as well as celiac artery and superior mesenteric artery peak systolic velocities and end-diastolic velocities alone, could predict a greater than or equal to 70% angiographic stenosis or occlusion or both. The results obtained by use of receiver operator curves indicated peak systolic velocity alone was an accurate predictor of splanchnic artery stenosis. Specifically, a peak systolic velocity greater than or equal to 275 cm/sec in the superior mesenteric artery and greater than or equal to 200 cm/sec in the celiac artery or no flow signal (superior mesenteric artery and celiac artery) predicted a 70% to 100% stenosis with sensitivity, specificity, and positive predictive values of 89%, 92%, and 80% for the superior mesenteric artery. Similar values for the celiac artery were 75%, 89%, and 85%, respectively. End-diastolic velocities or calculated velocity ratios conveyed no additional accuracy in predicting splanchnic artery stenosis.

  View details for Web of Science ID A1991GJ65700009

  View details for PubMedID 1920649

• LIMB SALVAGE VS AMPUTATION FOR CRITICAL ISCHEMIA - THE ROLE OF VASCULAR-SURGERY ARCHIVES OF SURGERY Taylor, L. M., HAMRE, D., Dalman, R. L., Porter, J. M. 1991; 126 (10): 1251-1258

  Abstract

  Since 1980, 498 patients with 627 critically ischemic legs (rest pain, gangrene, ischemic ulcer, and ankle-brachial pressure index less than 0.40) were treated with revascularization regardless of operative risk or anticipated operative difficulty. Primary amputation was performed only when no graftable distal vessels were present (14 primary amputations [2.8%]) or in neurologically impaired, hopelessly nonambulatory patients. The mortality for revascularization was 2.3%, and the median hospital stay was 11 days. During follow-up, 41 limbs (7%) required amputation, 31 after failure of revascularization and 10 despite patent revascularizations. Renal failure had an adverse influence on limb salvage (67%) because of a significantly increased requirement for amputation despite patent revascularizations. We conclude aggressive limb revascularization in patients with critical lower-extremity ischemia results in low operative morbidity and mortality and excellent long-term limb salvage. Patients with critical leg ischemia and renal failure are at higher risk for limb loss than patients without renal failure.

  View details for Web of Science ID A1991GJ52400014

  View details for PubMedID 1929826

• CHRONIC LOWER-EXTREMITY ISCHEMIA .2. CURRENT PROBLEMS IN SURGERY Porter, J. M., Mayberry, J. C., Taylor, L. M., Moneta, G. L., Cawthorn, S., Kozak, B., Rosch, J., Dalman, R. L., Yeager, R. A., DEFRANG, R. D. 1991; 28 (2): 93-179

  View details for Web of Science ID A1991EZ37800001

  View details for PubMedID 1993396

• SIMULTANEOUS OPERATIVE REPAIR OF MULTILEVEL LOWER-EXTREMITY OCCLUSIVE DISEASE JOURNAL OF VASCULAR SURGERY Dalman, R. L., Taylor, L. M., Moneta, G. L., Yeager, R. A., Porter, J. M. 1991; 13 (2): 211-221

  Abstract

  Sixty-two patients (39 men (63%), 23 women (27%), mean age 68 years) with multilevel lower extremity arterial occlusive disease underwent simultaneous inflow and outflow operative arterial repair consisting of aortofemoral bypass in 22 (35%), axillofemoral bypass in 17 (28%), femorofemoral bypass in 15 (24%), iliac endarterectomy in 7 (11%), and unilateral aortoiliac bypass in 1 (2%), combined with 69 outflow procedures (unilateral in 55 patients, 89%), including above-knee femoropopliteal in 12 (17%), below-knee femoropopliteal in 35 (51%), femoroinfrapopliteal in 20 (29%), popliteal tibial in 1 (1%), and femoropedal bypass in 1 (1%). Multiple criteria were used to identify patients with multilevel disease likely to benefit from multilevel procedures. The operations were performed by two operating teams in a median time of 240 minutes. Prosthetic grafts were used for eight (13%) distal bypasses, the remainder were autogenous vein. There was one operative death (1.8%). The mortality rate, morbidity rate, and operative time were not significantly different from a group of patients who underwent concurrent, isolated inflow operations (aortofemoral, axillobifemoral, femorofemoral bypass or iliac endarterectomy). Mean follow-up was 14.9 months (range, 0 to 120). The life-table primary patency for the inflow procedures was 92.6% at 24 months, the outflow was 94.9% at 24 months. Cumulative limb salvage was 90.9% at 48-month follow-up. All patients with claudication were relieved of their symptoms. We conclude that complete correction of multilevel disease can be accomplished with operative time, morbidity rate, and patency equal to that of single level repair. Multilevel procedures provide complete relief of symptoms in a higher percentage of patients than has been reported after single level repair.

  View details for Web of Science ID A1991EX03500004

  View details for PubMedID 1990162

• CHRONIC LOWER-EXTREMITY ISCHEMIA .1. CURRENT PROBLEMS IN SURGERY Porter, J. M., Mayberry, J. C., Taylor, L. M., Moneta, G. L., Cawthorn, S., Kozak, B., Rosch, J., Dalman, R. L., Yeager, R. A., DEFRANG, R. D. 1991; 28 (1): 1-92

  View details for Web of Science ID A1991EX00400001

  View details for PubMedID 1989777

• WILL INTERVENTIONAL ANGIOLOGY REPLACE VASCULAR-SURGERY ACTA CHIRURGICA SCANDINAVICA Dalman, R. L., Taylor, L. M., Porter, J. M. 1990: 25-35

  View details for Web of Science ID A1990DK07000006

  View details for PubMedID 2142367