Ronald L. Dalman MD, the Walter C. and Elsa R. Chidester Professor of Surgery

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

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

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

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

Abstract

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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

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

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

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

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. APPROACH AND RESULTS: 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 Web of Science ID 000316110400012

View details for PubMedID 23288157

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

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

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 ?(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

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

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

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

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

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 T?* 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

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

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

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-?/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

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

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?

View details for DOI 10.1177/1741826710389384

View details for Web of Science ID 000291026100013

View details for PubMedID 21450647

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

View details for Web of Science ID 000280089000192

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

View details for Web of Science ID 000263364700297

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

View details for Web of Science ID 000280089000461

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

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

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

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

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

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

View details for Web of Science ID 000252105700085

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

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

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

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

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

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

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

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

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

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

View details for Web of Science ID 000185810200015

View details for PubMedID 12958555

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

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

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

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

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

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

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

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

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

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

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

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

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

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

View details for Web of Science ID A1997YD48200016

View details for PubMedID 9363314

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

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

View details for Web of Science ID A1996VP69000038

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

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

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

View details for Web of Science ID A1995QK12800007

View details for PubMedID 8123465

View details for PubMedID 8268081

View details for PubMedID 8252228