Bio

Clinical Focus


  • Heart and Lung Transplantation
  • Valvular Heart Diseases
  • Coronary Artery Bypass
  • Thoracic Surgery
  • Adult Cardiac Surgery
  • Aortic Aneurysm
  • Arrhythmias, Cardiac

Academic Appointments


Honors & Awards


  • Regents’ Scholarship, University of California (1986-1990)
  • Alpha Omega Alpha, University of California, Irvine, School of Medicine (1990)
  • Walter Blumenson Award for Academic Promise, University of California, Irvine, School of Medicine (1990)
  • John Henry Smith Award, Resident of the Year, Stanford University Department of Surgery (1992)
  • Laubisch Fund for Cardiovascular Research, UCLA School of Medicine (2003-2005)
  • Stein-Oppenheimer Award, UCLA School of Medicine (2003)

Professional Education


  • Residency:Stanford University School of Medicine (1998) CA
  • Residency:Stanford University Hospital (1995) CA
  • Internship:Stanford University Hospital (1991) CA
  • Medical Education:University of California Irvine (1990) CA
  • Board Certification: Thoracic Surgery, American Board of Thoracic Surgery (2002)
  • Board Certification: Vascular Surgery, American Board of Surgery (1998)
  • Fellowship:UCLA - School of Medicine (2001) CA
  • Board Certification, Cardiothoracic Surgery, American Board of Thoracic Surgery (2002)
  • Board Certification: General Surgery, American Board of Surgery (1996)
  • Residency, UCLA, Cardiothoracic Surgery (2001)
  • Fellowship, Stanford University, Vascular Surgery (1998)
  • Residency, Stanford University, General Surgery (1995)
  • MD, University of California, Irvine, Medicine (Regents' Scholar) (1990)
  • MS, Univ. of California, Berkeley, Elec. Engin. Comp. Science (1983)
  • BS (Magna Cum Laude), Univ. of Michigan, Ann Arbor, Elec. Engin. Comp. Science

Teaching

2013-14 Courses


Graduate and Fellowship Programs


Publications

Journal Articles


  • Wirelessly powering miniature implants for optogenetic stimulation APPLIED PHYSICS LETTERS Yeh, A. J., Ho, J. S., Tanabe, Y., Neofytou, E., Beygui, R. E., Poon, A. S. 2013; 103 (16)

    View details for DOI 10.1063/1.4825272

    View details for Web of Science ID 000326148700092

  • Screening drug-induced arrhythmia events using human induced pluripotent stem cell-derived cardiomyocytes and low-impedance microelectrode arrays. Circulation Navarrete, E. G., Liang, P., Lan, F., Sanchez-Freire, V., Simmons, C., Gong, T., Sharma, A., Burridge, P. W., Patlolla, B., Lee, A. S., Wu, H., Beygui, R. E., Wu, S. M., Robbins, R. C., Bers, D. M., Wu, J. C. 2013; 128 (11): S3-13

    Abstract

    Drug-induced arrhythmia is one of the most common causes of drug development failure and withdrawal from market. This study tested whether human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) combined with a low-impedance microelectrode array (MEA) system could improve on industry-standard preclinical cardiotoxicity screening methods, identify the effects of well-characterized drugs, and elucidate underlying risk factors for drug-induced arrhythmia. hiPSC-CMs may be advantageous over immortalized cell lines because they possess similar functional characteristics as primary human cardiomyocytes and can be generated in unlimited quantities.Pharmacological responses of beating embryoid bodies exposed to a comprehensive panel of drugs at 65 to 95 days postinduction were determined. Responses of hiPSC-CMs to drugs were qualitatively and quantitatively consistent with the reported drug effects in literature. Torsadogenic hERG blockers, such as sotalol and quinidine, produced statistically and physiologically significant effects, consistent with patch-clamp studies, on human embryonic stem cell-derived cardiomyocytes hESC-CMs. False-negative and false-positive hERG blockers were identified accurately. Consistent with published studies using animal models, early afterdepolarizations and ectopic beats were observed in 33% and 40% of embryoid bodies treated with sotalol and quinidine, respectively, compared with negligible early afterdepolarizations and ectopic beats in untreated controls.We found that drug-induced arrhythmias can be recapitulated in hiPSC-CMs and documented with low impedance MEA. Our data indicate that the MEA/hiPSC-CM assay is a sensitive, robust, and efficient platform for testing drug effectiveness and for arrhythmia screening. This system may hold great potential for reducing drug development costs and may provide significant advantages over current industry standard assays that use immortalized cell lines or animal models.

    View details for DOI 10.1161/CIRCULATIONAHA.112.000570

    View details for PubMedID 24030418

  • 4-Year Results of a Randomized Controlled Trial of Percutaneous Repair Versus Surgery for Mitral Regurgitation JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Mauri, L., Foster, E., Glower, D. D., Apruzzese, P., Massaro, J. M., Herrmann, H. C., Hermiller, J., Gray, W., Wang, A., Pedersen, W. R., Bajwa, T., Lasala, J., Low, R., Grayburn, P., Feldman, T. 2013; 62 (4): 317-328

    Abstract

    This study sought to evaluate 4-year outcomes of percutaneous repair versus surgery for mitral regurgitation.Transcatheter therapies are being developed to treat valvular heart disease. In the EVEREST (Endovascular Valve Edge-to-Edge Repair Study) II trial, treatment of mitral valve regurgitation (MR) with a novel percutaneous device was compared with surgery and showed superior safety, but less reduction in MR at 1 year overall. We report the 4-year outcomes from the EVEREST II trial.Patients with grade 3+ or 4+ MR were randomly assigned to percutaneous repair with the MitraClip (Abbott, Menlo Park, California) device or conventional mitral valve surgery in a 2:1 ratio (184:95). Patients prospectively consented to 5 years of follow-up.At 4 years, the rate of the composite endpoint of freedom from death, surgery, or 3+ or 4+ MR in the intention-to-treat population was 39.8% versus 53.4% in the percutaneous repair group and surgical groups, respectively (p = 0.070). Rates of death were 17.4% versus 17.8% (p = 0.914), and 3+ or 4+ MR was present in 21.7% versus 24.7% (p = 0.745) at 4 years of follow-up, respectively. Surgery for mitral valve dysfunction, however, occurred in 20.4% versus 2.2% (p < 0.001) at 1 year and 24.8% versus 5.5% (p < 0.001) at 4 years.Patients treated with percutaneous repair of the mitral valve more commonly required surgery to treat residual MR; however, after the first year of follow-up, there were few surgeries required after either percutaneous or surgical treatment and no difference in the prevalence of moderate-severe and severe MR or mortality at 4 years. (Endovascular Valve Edge-to-Edge Repair Study [EVEREST II]; NCT00209274).

    View details for DOI 10.1016/j.jacc.2013.04.030

    View details for Web of Science ID 000322064100010

    View details for PubMedID 23665364

  • Robust pluripotent stem cell expansion and cardiomyocyte differentiation via geometric patterning Integrative Biolog Myers, F. B., Silver, J. S., Zhuge, Y., Beygui, R. E., Zarins, C. K., Lee, L. P., Abilez, O. J. 2013; 5 (12): 1495-506

    View details for DOI 10.1039/c2ib20191g

  • Right-ventricular failure following left ventricle assist device implantation CURRENT OPINION IN CARDIOLOGY Patlolla, B., Beygui, R., Haddad, F. 2013; 28 (2): 223-233

    Abstract

    To review recent insights on right-ventricular failure (RVF) following left-ventricular assist device (LVAD) implantation.Even with the availability of new generation continuous mechanical assist devices, RVF after implantation of LVAD is still associated with high morbidity and mortality. Recent studies have tried to better define the risk of RVF using combined clinical scores and measures of right-ventricular function or strain. Small exploratory studies have also investigated the role of pulmonary vasodilators and phosphodiesterase inhibitors in selected patients receiving LVAD implantation.Measure of right-ventricular function could improve the risk stratification of RVF following LVAD implantation. Future multicenter studies are needed to validate right-ventricular risk scores and to develop evidence-guided preventive and therapeutic strategies.

    View details for DOI 10.1097/HCO.0b013e32835dd12c

    View details for Web of Science ID 000314811800018

    View details for PubMedID 23337895

  • Robust pluripotent stem cell expansion and cardiomyocyte differentiation via geometric patterning INTEGRATIVE BIOLOGY Myers, F. B., Silver, J. S., Yan Zhuge, Z. G., Beygui, R. E., Zarins, C. K., Lee, L. P., Abilez, O. J. 2013; 5 (12): 1495-1506

    View details for DOI 10.1039/c2ib20191g

    View details for Web of Science ID 000327260600009

  • Protein-Polymer Hybrid Nanoparticles for Drug Delivery SMALL Ge, J., Neofytou, E., Lei, J., Beygui, R. E., Zare, R. N. 2012; 8 (23): 3573-3578

    Abstract

    Amphiphilic bovine serum albumin-poly(methyl methacrylate) conjugate forms nanoparticles with the uniform size of ~100 nm by self-assembling. Loaded with the hydrophobic anti-tumor drug camptothecin, the nanoparticle efficiently delivers drugs into cancer cells, and thus inhibits ~79% of tumor growth in animals compared with free drug.

    View details for DOI 10.1002/smll.201200889

    View details for Web of Science ID 000312214400004

    View details for PubMedID 22888073

  • Mediastinal goiter: a comprehensive study of 60 consecutive cases with special emphasis on identifying predictors of malignancy and sternotomy AMERICAN JOURNAL OF SURGERY Hajhosseini, B., Montazeri, V., Hajhosseini, L., Nezami, N., Beygui, R. E. 2012; 203 (4): 442-447

    Abstract

    We describe the clinical characteristics of patients with mediastinal goiter and our principles in surgical management of this pathology; we also identify the predictive factors of malignancy, sternotomy, and posterior mediastinal extension.We conducted a retrospective chart review of 60 patients with mediastinal goiter who underwent surgical intervention.Major perioperative complications were recurrent laryngeal nerve sacrifice (3.3%) and vagus nerve sacrifice (1.7%). A total of 12.7% of cases were malignant. The presence of dysphonia increased the likelihood of malignancy (P = .02), and malignancy was associated with a significant increase in sternotomy (P = .04) and nerve sacrifice (P < .001) during surgery. A history of thyroidectomy was a predictive factor for extension of the tumor to the posterior mediastinum (P = .02).Presenting with dysphonia is a predictor of malignancy that necessitates careful surgical planning because malignancy is associated with an increase in nerve injury and sternotomy during surgery.

    View details for DOI 10.1016/j.amjsurg.2011.03.010

    View details for Web of Science ID 000302913700006

    View details for PubMedID 21890099

  • Bilateral Thoracic Endometriosis Affecting the Lung and Diaphragm JSLS-JOURNAL OF THE SOCIETY OF LAPAROENDOSCOPIC SURGEONS Nezhat, C., King, L. P., Paka, C., Odegaard, J., Beygui, R. 2012; 16 (1): 140-142

    Abstract

    Endometriosis of the lung and the diaphragm is rare. Patients may present with symptoms such as shortness of breath, chest pain, and shoulder pain or they may be asymptomatic. Of note, there have been few reports of bilateral catamenial disease, and no reports, to our knowledge, of bilateral pathology proven pulmonary parenchymal endometriosis.A 43-year-old with stage IV endometriosis and large leiomyoma underwent a laparoscopic hysterectomy and treatment of endometrial lesions in 2005. In March and April of 2011, she presented with bilateral pneumothoraces. She subsequently underwent video-assisted thoracoscopy as well as resection and fulguration of bilateral lung and diaphragmatic endometriosis. Pathology confirmed endometrial implants in the lung parenchyma bilaterally.Catamenial pneumothorax is the most common presentation of thoracic endometriosis. However, bilateral catamenial pneumothoraces are rare. To the best of our knowledge, this case reflects the first report of pathology proven bilateral lung and diaphragm endometriosis.

    View details for DOI 10.4293/108680812X13291597716384

    View details for Web of Science ID 000307316100022

    View details for PubMedID 22906342

  • Drug Release from Electric-Field-Responsive Nanoparticles ACS NANO Ge, J., Neofytou, E., Cahill, T. J., Beygui, R. E., Zare, R. N. 2012; 6 (1): 227-233

    Abstract

    We describe a new temperature and electric field dual-stimulus responsive nanoparticle system for programmed drug delivery. Nanoparticles of a conducting polymer (polypyrrole) are loaded with therapeutic pharmaceuticals and are subcutaneously localized in vivo with the assistance of a temperature-sensitive hydrogel (PLGA-PEG-PLGA). We have shown that drug release from the conductive nanoparticles is controlled by the application of a weak, external DC electric field. This approach represents a novel interactive drug delivery system that can show an externally tailored release profile with an excellent spatial, temporal, and dosage control.

    View details for DOI 10.1021/nn203430m

    View details for Web of Science ID 000299368300029

    View details for PubMedID 22111891

  • Successful use of a pneumatic biventricular assist device as a bridge to transplantation in cardiogenic shock JOURNAL OF HEART AND LUNG TRANSPLANTATION Moriguchi, J., Davis, S., Jocson, R., Esmailian, F., Ardehali, A., Laks, H., Kwon, M., Kittleson, M., Kobashigawa, J., Patel, J., Marelli, D., Plunkett, M., Beygui, R., Shemin, R. 2011; 30 (10): 1143-1147

    Abstract

    Mechanical circulatory support is a highly effective technology to maintain organ perfusion in patients with cardiogenic shock as a bridge to transplantation. Although implantation of a left ventricular assist device alone is often the preferred configuration, patients with biventricular failure and significant end-organ dysfunction often require biventricular assistance.Between January 2000 and September 2008, 80 patients with severe biventricular failure were accepted for heart transplantation and received a pneumatic biventricular assist devices as a bridge to transplant. Patients were retrospectively divided into 2 groups: those successfully bridged to transplant (Group A) and those who died (Group B). Patients were also divided into 2 periods of implantation: Group X (2000-2005) and Group Y (2006-2008, which used a multidiscipline selection process).Overall success rate to transplantation was 71.3%, with Group Y demonstrating an 82% success to transplant rate vs 63% in Group X. One-year actuarial survival after transplant was 89% compared with 92% in patients without a ventricular assist device. There were no statistically significant laboratory parameters between Groups A and B identifying potential risk factors for poor outcome.Biventricular assist device therapy represents an effective and reliable means of supporting selected Interagency Registry for Mechanically Assisted Circulatory Support profile 1 patients as a bridge to transplantation, with excellent success to transplant rates and post-transplant survival.

    View details for DOI 10.1016/j.healun.2011.04.005

    View details for Web of Science ID 000295859400007

    View details for PubMedID 21640618

  • Adipose tissue-derived stem cells display a proangiogenic phenotype on 3D scaffolds. Journal of biomedical materials research. Part A Neofytou, E. A., Chang, E., Patlola, B., Joubert, L., Rajadas, J., Gambhir, S. S., Cheng, Z., Robbins, R. C., Beygui, R. E. 2011; 98 (3): 383-393

    Abstract

    Ischemic heart disease is the leading cause of death worldwide. Recent studies suggest that adipose tissue-derived stem cells (ASCs) can be used as a potential source for cardiovascular tissue engineering due to their ability to differentiate along the cardiovascular lineage and to adopt a proangiogenic phenotype. To understand better ASCs' biology, we used a novel 3D culture device. ASCs' and b.END-3 endothelial cell proliferation, migration, and vessel morphogenesis were significantly enhanced compared to 2D culturing techniques. ASCs were isolated from inguinal fat pads of 6-week-old GFP+/BLI+ mice. Early passage ASCs cells (P3-P4), PKH26-labeled murine b.END-3 cells or a co-culture of ASCs and b.END-3 cells were seeded at a density of 1 × 10(5) on three different surface configurations: (a) a 2D surface of tissue culture plastic, (b) Matrigel, and (c) a highly porous 3D scaffold fabricated from inert polystyrene. VEGF expression, cell proliferation, and tubulization, were assessed using optical microscopy, fluorescence microscopy, 3D confocal microscopy, and SEM imaging (n = 6). Increased VEGF levels were seen in conditioned media harvested from co-cultures of ASCs and b.END-3 on either Matrigel or a 3D matrix. Fluorescence, confocal, SEM, bioluminescence revealed improved cell, proliferation, and tubule formation for cells seeded on the 3D polystyrene matrix. Collectively, these data demonstrate that co-culturing ASCs with endothelial cells in a 3D matrix environment enable us to generate prevascularized tissue-engineered constructs. This can potentially help us to surpass the tissue thickness limitations faced by the tissue engineering community today.

    View details for DOI 10.1002/jbm.a.33113

    View details for PubMedID 21630430

  • A matrix micropatterning platform for cell localization and stem cell fate determination ACTA BIOMATERIALIA Huang, N. F., Patlolla, B., Abilez, O., Sharma, H., Rajadas, J., Beygui, R. E., Zarins, C. K., Cooke, J. P. 2010; 6 (12): 4614-4621

    Abstract

    To study the role of cell-extracellular matrix (ECM) interactions, microscale approaches provide the potential to perform high throughput assessment of the effect of the ECM microenvironment on cellular function and phenotype. Using a microscale direct writing (MDW) technique, we characterized the generation of multicomponent ECM microarrays for cellular micropatterning, localization and stem cell fate determination. ECMs and other biomolecules of various geometries and sizes were printed onto epoxide-modified glass substrates to evaluate cell attachment by human endothelial cells. The endothelial cells displayed strong preferential attachment to the ECM patterned regions and aligned their cytoskeleton along the direction of the micropatterns. We next generated ECM microarrays that contained one or more ECM components (namely gelatin, collagen IV and fibronectin) and then cultured murine embryonic stem cell (ESCs) on the microarrays. The ESCs selectively attached to the micropatterned features and expressed markers associated with a pluripotent phenotype, such as E-cadherin and alkaline phosphatase, when maintained in growth medium containing leukemia inhibitory factor. In the presence of the soluble factors retinoic acid and bone morphogenetic protein-4 the ESCs differentiated towards the ectodermal lineage on the ECM microarray with differential ECM effects. The ESCs cultured on gelatin showed significantly higher levels of pan cytokeratin expression, when compared with cells cultured on collagen IV or fibronectin, suggesting that gelatin preferentially promotes ectodermal differentiation. In summary, our results demonstrate that MDW is a versatile approach to print ECMs of diverse geometries and compositions onto surfaces, and it is amenable to the generation of multicomponent ECM microarrays for stem cell fate determination.

    View details for DOI 10.1016/j.actbio.2010.06.033

    View details for Web of Science ID 000284385300018

    View details for PubMedID 20601236

  • A prospective, randomized, crossover pilot study of inhaled nitric oxide versus inhaled prostacyclin in heart transplant and lung transplant recipients JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Khan, T. A., Schnickel, G., Ross, D., Bastani, S., Laks, H., Esmailian, F., Marelli, D., Beygui, R., Shemin, R., Watson, L., Vartapetian, I., Ardehali, A. 2009; 138 (6): 1417-1424

    Abstract

    Inhaled nitric oxide has been shown to reduce pulmonary vascular resistance in patients undergoing cardiothoracic surgery, but it is limited by toxicity, the need for special monitoring, and cost. Inhaled prostacyclin also decreases pulmonary artery pressure, is relatively free of toxicity, requires no specific monitoring, and is less expensive. The objective of this study was to compare nitric oxide and prostacyclin in the treatment of pulmonary hypertension, refractory hypoxemia, and right ventricular dysfunction in thoracic transplant recipients in a prospective, randomized, crossover pilot trial.Heart transplant and lung transplant recipients were randomized to nitric oxide or prostacyclin as initial treatment, followed by a crossover to the other agent after 6 hours. Pulmonary vasodilators were initiated in the operating room for pulmonary hypertension, refractory hypoxemia, or right ventricular dysfunction. Nitric oxide was administered at 20 ppm, and prostacyclin was administered at 20,000 ng/mL. Hemodynamic and oxygenation parameters were recorded before and after initiation of pulmonary vasodilator therapy. At 6 hours, the hemodynamic and oxygenation parameters were recorded again, just before discontinuing the initial agent. Crossover baseline parameters were measured 30 minutes after the initial agent had been stopped. The crossover agent was then started, and the hemodynamic and oxygenation parameters were measured again 30 minutes later.Heart transplant and lung transplant recipients (n = 25) were randomized by initial treatment (nitric oxide, n = 14; prostacyclin, n = 11). Nitric oxide and prostacyclin both reduced pulmonary artery pressure and central venous pressure, and improved cardiac index and mixed venous oxygen saturation on initiation of therapy. More importantly, at the 6-hour crossover trial, there were no significant differences between nitric oxide and prostacyclin in the reduction of pulmonary artery pressures or central venous pressure, or in improvement in cardiac index or mixed venous oxygen saturation. Nitric oxide and prostacyclin did not affect the oxygenation index or systemic blood pressure. There were no complications associated with nitric oxide or prostacyclin.In heart transplant and lung transplant recipients, nitric oxide and prostacyclin similarly reduce pulmonary artery pressures and central venous pressure, and improve cardiac index and mixed venous oxygen saturation. Inhaled prostacyclin may offer an alternative to nitric oxide in the treatment of pulmonary hypertension in thoracic transplantation.

    View details for DOI 10.1016/j.jtcvs.2009.04.063

    View details for Web of Science ID 000272029800021

    View details for PubMedID 19931670

  • On-Pump versus Off-Pump Coronary-Artery Bypass Surgery. NEW ENGLAND JOURNAL OF MEDICINE Shroyer, A. L., Grover, F. L., Hattler, B., Collins, J. F., McDonald, G. O., Kozora, E., Lucke, J. C., Baltz, J. H., Novitzky, D. 2009; 361 (19): 1827-1837

    Abstract

    Coronary-artery bypass grafting (CABG) has traditionally been performed with the use of cardiopulmonary bypass (on-pump CABG). CABG without cardiopulmonary bypass (off-pump CABG) might reduce the number of complications related to the heart-lung machine.We randomly assigned 2203 patients scheduled for urgent or elective CABG to either on-pump or off-pump procedures. The primary short-term end point was a composite of death or complications (reoperation, new mechanical support, cardiac arrest, coma, stroke, or renal failure) before discharge or within 30 days after surgery. The primary long-term end point was a composite of death from any cause, a repeat revascularization procedure, or a nonfatal myocardial infarction within 1 year after surgery. Secondary end points included the completeness of revascularization, graft patency at 1 year, neuropsychological outcomes, and the use of major resources.There was no significant difference between off-pump and on-pump CABG in the rate of the 30-day composite outcome (7.0% and 5.6%, respectively; P=0.19). The rate of the 1-year composite outcome was higher for off-pump than for on-pump CABG (9.9% vs. 7.4%, P=0.04). The proportion of patients with fewer grafts completed than originally planned was higher with off-pump CABG than with on-pump CABG (17.8% vs. 11.1%, P<0.001). Follow-up angiograms in 1371 patients who underwent 4093 grafts revealed that the overall rate of graft patency was lower in the off-pump group than in the on-pump group (82.6% vs. 87.8%, P<0.01). There were no treatment-based differences in neuropsychological outcomes or short-term use of major resources.At 1 year of follow-up, patients in the off-pump group had worse composite outcomes and poorer graft patency than did patients in the on-pump group. No significant differences between the techniques were found in neuropsychological outcomes or use of major resources. (ClinicalTrials.gov number, NCT00032630.).

    View details for Web of Science ID 000271405800007

    View details for PubMedID 19890125

  • The use of three-dimensional nanostructures to instruct cells to produce extracellular matrix for regenerative medicine strategies BIOMATERIALS Schenke-Layland, K., Rofail, F., Heydarkhan, S., Gluck, J. M., Ingle, N. P., Angelis, E., Choi, C., MacLellan, W. R., Beygui, R. E., Shemin, R. J., Heydarkhan-Hagvall, S. 2009; 30 (27): 4665-4675

    Abstract

    Synthetic polymers or naturally-derived extracellular matrix (ECM) proteins have been used to create tissue engineering scaffolds; however, the need for surface modification in order to achieve polymer biocompatibility and the lack of biomechanical strength of constructs built using proteins alone remain major limitations. To overcome these obstacles, we developed novel hybrid constructs composed of both strong biosynthetic materials and natural human ECM proteins. Taking advantage of the ability of cells to produce their own ECM, human foreskin fibroblasts were grown on silicon-based nanostructures exhibiting various surface topographies that significantly enhanced ECM protein production. After 4 weeks, cell-derived sheets were harvested and histology, immunochemistry, biochemistry and multiphoton imaging revealed the presence of collagens, tropoelastin, fibronectin and glycosaminoglycans. Following decellularization, purified sheet-derived ECM proteins were mixed with poly(epsilon-caprolactone) to create fibrous scaffolds using electrospinning. These hybrid scaffolds exhibited excellent biomechanical properties with fiber and pore sizes that allowed attachment and migration of adipose tissue-derived stem cells. Our study represents an innovative approach to generate strong, non-cytotoxic scaffolds that could have broad applications in tissue regeneration strategies.

    View details for DOI 10.1016/j.biomaterials.2009.05.033

    View details for Web of Science ID 000269330400026

    View details for PubMedID 19524289

  • Endometriosis of the Diaphragm: Four Cases Treated with a Combination of Laparoscopy and Thoracoscopy JOURNAL OF MINIMALLY INVASIVE GYNECOLOGY Nezhat, C., Nicoll, L. M., Bhagan, L., Huang, J. Q., Bosev, D., Hajhosseini, B., Beygui, R. E. 2009; 16 (5): 573-580

    Abstract

    We aim to describe the clinical characteristics and the principles of combined laparoscopic and thoracoscopic management of women with diaphragmatic endometriosis at our institution.Case series (Canadian Task Force Classification II2).Tertiary care referral center.Four women with diaphragmatic endometriosis.Laparoscopy and thoracoscopy.We retrospectively reviewed the charts of 4 consecutive women with diaphragmatic endometriosis who underwent laparoscopy and thoracoscopy from June 2008 through September 2008.Four patients underwent a combination of laparoscopy for treatment of abdominopelvic endometriosis and thoracoscopy for treatment of diaphragmatic endometriosis. All patients had a history of chest pain. Three had a history of pelvic pain. Two had a history of catamenial hemothorax or pneumothorax. Two had been previously diagnosed with endometriosis, and three had a history of hormonal pharmacotherapy. All underwent laparoscopy and thoracoscopy without complications. All had uneventful recoveries. At nine-month follow-up, all patients were free of chest pain, and one patient had recurring pelvic pain.To the best of our knowledge, this constitutes the only reported series of patients with endometriosis who underwent a procedure systematically combining both laparoscopy and thoracoscopy for treatment of abdominopelvic and thoracic disease. It confirms that combined laparoscopic and thoracoscopic diagnosis and management of diaphragmatic endometriosis is reasonable. The inferior aspect of the diaphragm should be evaluated in all patients undergoing laparoscopy for endometriosis. Concomitant thoracoscopy should be considered for all patients with history of catamenial hemopneumothorax, cyclic chest or shoulder pain, or cyclic dyspnea. The aim of treatment should be to remove endometriotic lesions, to provide symptomatic relief, and to avoid recurrence. The use of these minimally invasive techniques may reduce the need for laparotomy or thoracotomy in affected patients.

    View details for DOI 10.1016/j.jmig.2009.06.012

    View details for Web of Science ID 000269938300011

    View details for PubMedID 19835800

  • Tricuspid valve regurgitation after heart transplantation JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Marelli, D., Esmailian, F., Wong, S. Y., Kobashigawa, J. A., Kwon, M. H., Beygui, R. E., Laks, H., Plunkett, M. D., Ardehali, A., Shemin, R. J. 2009; 137 (6): 1557-1559

    View details for DOI 10.1016/j.jtcvs.2008.09.012

    View details for Web of Science ID 000266275200043

    View details for PubMedID 19464484

  • Cell growth as a sheet on three-dimensional sharp-tip nanostructures JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A Choi, C., Heydarkhan-Hagvall, S., Wu, B. M., Dunn, J. C., Beygui, R. E., Kim, C. ". 2009; 89A (3): 804-817

    Abstract

    Cells in vivo encounter with and react to the extracellular matrix materials on a nanometer scale. Recent advances in nanofabrication technologies allowing the precise control of a nanostructure's pattern, periodicity, shape, and height have enabled a systematic study of cell interactions with three-dimensional nanotopographies. In this report, we examined the behavior of human foreskin fibroblasts on well-ordered dense arrays (post and grate patterns with a 230-nm pitch) of sharp-tip nanostructures with varying three-dimensionalities (from 50 to 600 nm in structural height) over time-until a cell sheet was formed. Although cells started out smaller and proliferated slower on tall nanostructures (both posts and grates) than on smooth surfaces, they became confluent to form a sheet in 3 weeks. On grate patterns, significant cell elongation in alignment with the underlying pattern was observed and maintained over time. On tall nanostructures, cells grew while raised on sharp tips, resulting in a weak total adherence to the solid surface. A sheet of cells was easily peeled off from such surfaces, suggesting that nanoscale topographies can be used as the basis for cell-sheet tissue engineering.

    View details for DOI 10.1002/jbm.a.32101

    View details for Web of Science ID 000265895300026

  • Endometriosis of the Diaphragm: Four Cases Treated with a Combination of Laparoscopy and Thoracoscopy Journal of Minimally Invasive Gynecology Camran Nezhat, inda M. Nicoll, Lisa Bhagan, Jian Qun Huang, Dorian Bosev, Babak Hajhosseini, Ramin E. Beygui 2009; 16 (5): 573-580
  • The role of cytoprotective cytokines in cardiac ischemia/reperfusion injury JOURNAL OF SURGICAL RESEARCH Anderson, C. D., Heydarkhan-Hagvall, S., Schenke-Layland, K., Yang, J. Q., Jordan, M. C., Kim, J. K., Brown, D. A., Zuk, P. A., Laks, H., Roos, K. P., MacLellan, W. R., Beygui, R. E. 2008; 148 (2): 164-171

    Abstract

    The mechanism(s) underlying the beneficial effects of adult mesenchymal stem cells (MSCs) after myocardial infarction (MI) is poorly understood. One possible explanation is the ability of MSCs to secrete cytokines, which modulate cardiomyocyte survival and function. MSCs express at least two cytoprotective cytokines, hepatocyte growth factor (HGF) and stromal cell-derived factor-1 alpha (CXCL12). The aim of our study was to compare the effects of these two cytokines administered acutely post-MI. We subjected adult male Lewis rats to myocardial ischemia/reperfusion injury. Immediately upon reperfusion, polymers saturated with HGF or CXCL12 were placed onto the infarcted anterior wall and the rats were allowed to recover. Echocardiographic analysis at 4 wk post-MI to assess left ventricular (LV) function revealed that LV ejection fraction was increased in the HGF treated group compared with the phosphate-buffered saline (PBS) control group. Likewise, LV end diastolic dimension was reduced in the HGF treated group compared with the PBS control group. Similarly, invasive hemodynamics at 12 wk showed improved contractility and relaxation in the HGF treated group compared with the PBS control group. In contrast, no significant effect on LV function was seen in the CXCL12 treated group. To determine the potential mechanism for this effect, infarct size (IFS) at 72 h was determined. IFS was decreased 4.2-fold in the HGF treated group compared with the PBS control group. Thus, HGF acutely post-MI using polymer delivery reduces IFS, leading to beneficial effects on post-MI LV remodeling.

    View details for DOI 10.1016/j.jss.2007.08.005

    View details for Web of Science ID 000257725100010

    View details for PubMedID 18067924

  • Long-term outcomes of heart transplantation in older recipients JOURNAL OF HEART AND LUNG TRANSPLANTATION Marelli, D., Kobashigawa, J., Hamilton, M. A., Moriguchi, J. D., Kermani, R., Ardehali, A., Patel, J., Noguchi, E., Beygui, R., Laks, H., Plunkett, M., Shemin, R., Esmailian, F. 2008; 27 (8): 830-834

    Abstract

    Heart transplantation in the elderly is increasingly common. In the mid-1990s, 25% of recipients in our program were >62 years of age. We evaluated outcomes from one institution with the hypothesis that older recipients may be at higher risk of major complications associated with immunosuppression.We analyzed results for 182 patients aged 62 to 75 years (mean +/- SD: 66.3 +/- 11.4 years) who underwent heart transplantation between January 1995 and July 2001 at a single institution. They were compared with a control group of 348 contemporaneous adult recipients aged 18 to 62 years (mean +/- SD: 48.2 +/- 11.4 years). All recipients in this consecutive cohort had a follow-up of at least at least 5 years. End-points studied were Kaplan-Meier survival, freedom from dialysis and freedom from malignancy at 100 months. Follow-up was 100% at 100 months.At 100 months, survival for the elderly was 55% (46 remaining at risk) and 63% (102 remaining at risk) for controls (p = 0.051, log-rank test). Re-transplant and dialysis, but not recipient age or malignancy, were predictive of survival by regression analysis (p = 0.003, p < 0.001, p = 0.53 and p = 0.84, respectively). Freedom from malignancy at 100 months was 68% for the elderly and 95% for controls (p < 0.001). Age predicted malignancy by regression analysis (p < 0.001). At 100 months, freedom from dialysis was 81% for the elderly and 87% for controls (p = 0.005). Pre-operative creatinine, but not age, was predictive of need for dialysis (p = 0.003 and p = 0.47, respectively).Although long-term survival of older heart transplant recipients is acceptable, it is significantly lower than in young recipients. The increased risk of renal failure and malignancy among elderly patients likely influences the difference in survival observed between the two groups. Pre-operative renal function warrants careful consideration. As ventricular assist device technology improves, it may be used to complement heart transplantation to avoid immunosuppression and its side effect of malignancy in older patients with advanced heart failure.

    View details for DOI 10.1016/j.healun.2008.05.006

    View details for Web of Science ID 000258241200003

    View details for PubMedID 18656794

  • Three-dimensional electrospun ECM-based hybrid scaffolds for cardiovascular tissue engineering BIOMATERIALS Heydarkhan-Hagvall, S., Schenke-Layland, K., Dhanasopon, A. P., Rofail, F., Smith, H., Wu, B. M., Shemin, R., Beygui, R. E., MacLellan, W. R. 2008; 29 (19): 2907-2914

    Abstract

    Electrospinning using natural proteins or synthetic polymers is a promising technique for the fabrication of fibrous scaffolds for various tissue engineering applications. However, one limitation of scaffolds electrospun from natural proteins is the need to cross-link with glutaraldehyde for stability, which has been postulated to lead to many complications in vivo including graft failure. In this study, we determined the characteristics of hybrid scaffolds composed of natural proteins including collagen and elastin, as well as gelatin, and the synthetic polymer poly(epsilon-caprolactone) (PCL), so to avoid chemical cross-linking. Fiber size increased proportionally with increasing protein and polymer concentrations, whereas pore size decreased. Electrospun gelatin/PCL scaffolds showed a higher tensile strength when compared to collagen/elastin/PCL constructs. To determine the effects of pore size on cell attachment and migration, both hybrid scaffolds were seeded with adipose-derived stem cells. Scanning electron microscopy and nuclei staining of cell-seeded scaffolds demonstrated the complete cell attachment to the surfaces of both hybrid scaffolds, although cell migration into the scaffold was predominantly seen in the gelatin/PCL hybrid. The combination of natural proteins and synthetic polymers to create electrospun fibrous structures resulted in scaffolds with favorable mechanical and biological properties.

    View details for DOI 10.1016/j.biomaterials.2008.03.034

    View details for Web of Science ID 000256144900010

    View details for PubMedID 18403012

  • Lung transplantation in older patients? JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Mahidhara, R., Bastani, S., Ross, D. J., Saggar, R., Lynch, J., Schnickel, G. T., Gjertson, D., Beygui, R., Ardehali, A. 2008; 135 (2): 412-420

    Abstract

    Age 65 years and older is generally considered a contraindication to lung transplantation. Our group has offered lung transplantation to select patients 65 years of age and older who lack other comorbid conditions. We sought to define the short- and medium-term outcome of lung transplantation in patients aged 65 years and older.We reviewed the records of our lung transplant recipients from March 2000 to September 2006. During this interval, 50 patients were 65 years or older at the time of transplantation. Fifty patients younger than 65 years were matched to the older cohort by means of propensity analysis. The demographics and perioperative and postoperative characteristics and survival of the 2 groups were compared.Older patients were more likely to receive single-lung transplantation (older group: 76% vs younger group: 16%, P < .05) and nonstandard donor lungs (older group: 46% vs younger group: 28%, P = .06). The composite in-hospital morbidity rate was similar in the older and younger groups. There was no significant difference in the early oxygenation parameters, incidence of acute cellular rejection, or incidence of bronchiolitis obliterans syndrome between the 2 groups. The early survival of the older patients was 95.7% compared with 95.9% in the younger cohort (P = .73). The 1-year survival of the 2 groups was also similar (older group: 79.7% vs younger group: 91.2%, P = .16). The 3-year survival of the older and younger recipients was 73.6% and 74.2%, respectively (P = .64). There were 8 deaths in the older recipient group during the 1-month to 1-year posttransplantation interval, predominantly because of infections.Lung transplantation can be performed in patients older than 65 years with acceptable clinical outcomes. The "increased" mortality of older patients between 1 month and 1 year after transplantation, predominantly from infectious causes, might be due to immunosenescence of older patients. This finding warrants adjustments in the immunosuppression protocol of older patients undergoing lung transplantation. The effect of offering lung transplantation to older patients on donor lung availability deserves further investigation.

    View details for DOI 10.1016/j.jtcvs.2007.09.030

    View details for Web of Science ID 000252830400026

    View details for PubMedID 18242277

  • Human adipose stem cells: A potential cell source for cardiovascular tissue engineering CELLS TISSUES ORGANS Heydarkhan-Hagvall, S., Schenke-Layland, K., Yang, J. Q., Heydarkhan, S., Xu, Y., Zuk, P. A., MacLellan, W. R., Beygui, R. E. 2008; 187 (4): 263-274

    Abstract

    A crucial step in providing clinically relevant applications of cardiovascular tissue engineering involves the identification of a suitable cell source. The objective of this study was to identify the exogenous and endogenous parameters that are critical for the differentiation of human adipose stem cells (hASCs) into cardiovascular cells.hASCs were isolated from human lipoaspirate samples, analyzed, and subjected to two differentiation protocols.As shown by fluorescence-activated cell sorter (FACS) analysis, a population of hASCs expressed stem cell markers including CXCR4, CD34, c-kit, and ABCG2. Further, FACS and immunofluorescence analysis of hASCs, cultured for 2 weeks in DMEM-20%-FBS, showed the expression of smooth muscle cell (SMC)-specific markers including SM alpha-actin, basic calponin, h-caldesmon and SM myosin. hASCs, cultured for 2 weeks in endothelial cell growth medium-2 (EGM-2), formed a network of branched tube-like structures positive for CD31, CD144, and von Willebrand factor. The frequency of endothelial cell (EC) marker-expressing cells was passage number-dependent. Moreover, hASCs attached and formed a confluent layer on top of electrospun collagen-elastin scaffolds. Scanning electron microscopy and DAPI staining confirmed the integration of hASCs with the fibers and formation of a cell-matrix network.Our results indicate that hASCs are a potential cell source for cardiovascular tissue engineering; however, the differentiation capacity of hASCs into SMCs and ECs is passage number- and culture condition-dependent.

    View details for DOI 10.1159/000113407

    View details for Web of Science ID 000255586200004

    View details for PubMedID 18196894

  • Hypoxic cell death is reduced by pH buffering in a model of engineered heart tissue ARTIFICIAL CELLS BLOOD SUBSTITUTES AND BIOTECHNOLOGY Brown, D. A., MacLellan, W. R., Dunn, J. C., Wu, B. M., Beygui, R. E. 2008; 36 (2): 94-113

    Abstract

    In this report, we tested the ability of HEPES-buffered culture medium to reduce acidotic cell death in hypoxic monolayer cell cultures and in a diffusion-limited model of engineered heart tissue (EHT).Neonatal rat cardiomyocytes were either plated (monolayers) or suspended in a hydrogel disc containing HEPES.Monolayers cultured in 0% oxygen exhibited a pH drop to 5.46 +/- 0.27 after 4 days with no HEPES, or 7.11 +/- 0.09 with 50 mM HEPES. The lowest observed pH in EHTs was estimated as 6.2 with no HEPES and 7.1 with 50 mM HEPES, which were endpoints of noticeably different pH gradients across the EHTs. Addition of HEPES to hypoxic monolayers corresponded with fewer propidium iodide-positive cells and TUNEL-positive cells; addition of HEPES to EHTs resulted in greater calcein staining and less LDH release.Effective pH buffering reduces cell death by attenuating the acidosis that accompanies anaerobic metabolism.

    View details for DOI 10.1080/10731190801932090

    View details for Web of Science ID 000255001200002

    View details for PubMedID 18437587

  • Donor brain death mechanisms and outcomes after heart transplantation TRANSPLANTATION PROCEEDINGS Cohen, O., De La Zerda, D. J., Beygui, R., Hekmat, D., Laks, H. 2007; 39 (10): 2964-2969

    Abstract

    We sought to explore whether the cause of donor brain death influenced recipient outcomes after cardiac transplantation. In retrospect, 358 consecutive donors provided cardiac allografts to adult patients undergoing orthotopic heart transplantation at a single urban US medical center from January 2000 through December 2005. Alternate recipients were excluded. Mechanism and cause of donor brain injury and death were divided into five categories: anoxia (nontraumatic) (n=36), blunt head trauma (n=220), penetrating head trauma (n=83), brain tumor/infection (n=7), and cerebrovascular event (n=12). The five subgroups were categorized as traumatic or nontraumatic. The end points of the study were causes of early and late mortality, survival, and rejection rate. There were 59 deaths in the 6-year period. Total and short-term recipient mortality were found to be statistically higher among heart transplant recipients when the donors suffered from traumatic brain death compared to those whose brain death etiology was nontraumatic (P=.045, P=.033, respectively). Rejection rate was similar in all groups (P=.497). In conclusion, donor traumatic brain death was found to be a valid risk factor for recipient mortality after heart transplantation. Caution should be used when evaluating such donors, particularly in the presence of other risk factors.

    View details for DOI 10.1016/j.transproceed.2007.08.102

    View details for Web of Science ID 000252037900004

    View details for PubMedID 18089301

  • Ethnicity as a predictor of graft longevity and recipient mortality in heart transplantation TRANSPLANTATION PROCEEDINGS Cohen, O., De La Zerda, D., Beygui, R. E., Hekmat, D., Laks, H. 2007; 39 (10): 3297-3302

    Abstract

    There is a dearth of data about the effect of donor and recipient ethnicity on survival and rejection rate after clinical heart transplantation, although the subject had been partly studied before. We compared the mortality and rejection rate among different ethnic groups at our institution.In retrospect, 525 consecutive donors provided cardiac allografts to adult and pediatric patients undergoing orthotropic heart transplantation at a single, urban US medical center between 2000 and 2005. Donors and recipients were categorized according to ethnicity: African American, Asian, Caucasian, Hispanic, and Others (Indian, Mediterranean/Arabic, Afghans). Donor and recipient ethnicity-as an independent factor and the interaction between them-were examined as a risk factor for mortality and rejection after heart transplantation. Mean follow-up period was 3.2+/-1.9 years (range, 0.1 to 6.6). All recipients received triple immunosuppression consisting of a calcineurin inhibitor, an antiproliferative agent, and steroids. No patients received induction immunotherapy. The end points of the study were early and late mortality, rejection rate, and rejection-free survival time.The overall mortality was 17.3% (91 patients). Recipient mortality rate according to donor race was: African American, 23.1%; Asian, 11.1%; Caucasian, 18.7%; and Hispanic, 14.6%. No statistical significance was found, although the mortality differences presented. Recipient mortality with regard to recipients ethnicity was: African American, 22.2%; Asian, 6.3%; Caucasian, 18%; Hispanic, 18.9%; and others 40% (P=.048). Donor-recipient race match was not found as a risk factor influencing mortality as the matched group mortality was 17.5% comparing with the mismatched group mortality of 17.8% (P=.874). The overall rejection rate was 3.8% (20 rejection events). Rejection rate according donor race was: African American, 7.7%; Asian, 10.7%; Caucasian, 4%; and Hispanic, 1.3% (P=.027). Rejection rate with respect to recipients ethnicity was: African American, 0; Asian, 3.2%; Caucasian, 4.4%; Hispanic, 2.7%; and others, 20% with no statistical significance (P=.236). Donor recipient race match was not found as a risk factor influencing rejection rate (P=.58).Recipients' ethnicity was found as a significant risk factor for mortality. Rejection rate were found higher among the African American donors and significantly lower in the Hispanic donors. Significantly lower mortality rate was found among Asian recipients. Donor-recipient race match did not influence the mortality or rejection rate.

    View details for DOI 10.1016/j.transproceed.2007.06.086

    View details for Web of Science ID 000252037900078

    View details for PubMedID 18089375

  • Analysis of pH gradients resulting from mass transport limitations in engineered heart tissue ANNALS OF BIOMEDICAL ENGINEERING Brown, D. A., MacLellan, W. R., Wu, B. M., Beygui, R. E. 2007; 35 (11): 1885-1897

    Abstract

    Transport limitations of critical nutrients are a major obstacle in the construction of engineered heart tissues (EHTs), and the importance of oxygen in this regard is well-documented throughout the literature. An indirect effect of cellular hypoxia is the shunt to the less-efficient glycolytic metabolism, which is accompanied by a reduction in extracellular pH. Image analysis of phenol red coloration in an experimental model of EHTs demonstrated pH gradients towards the center of the construct, which were dependent on experimental variables. Based on these observations, a four-species, 2-D diffusion-reaction mathematical model was developed to predict pH in a radial-diffusion model. The mathematical model predicted lethal values of pH (<6.5) in EHTs comprised of a nominal cell density of 10(6) cells/cm(3). pH predictions were moderately dependent on O(2) concentration, and strongly dependent on cell density, CO(2) concentration, and diffusion path length. It can be concluded from this study that hypoxia-induced acidosis is an important element in the mass transport problem, and future experiments measuring pH with more sensitive methods is expected to further elucidate the extent of this effect.

    View details for DOI 10.1007/s10439-007-9360-4

    View details for Web of Science ID 000250372400004

    View details for PubMedID 17680364

  • Influence of systematically varied nano-scale topography on cell morphology and adhesion CELL COMMUNICATION AND ADHESION Heydarkhan-Hagvall, S., Chof, C., Dunn, J., Heydarkhan, S., Schenke-Layland, K., MacLellan, W. R., Beygul, R. E. 2007; 14 (5): 181-194

    Abstract

    The types of cell-matrix adhesions and the signals they transduce strongly affect the cell-phenotype. We hypothesized that cells sense and respond to the three-dimensionality of their environment, which could be modulated by nano-structures on silicon surfaces. Human foreskin fibroblasts were cultured on nano-structures with different patterns (nano-post and nano-grate) and heights for 3 days. The presence of integrin alpha(5), beta(1), beta(3), paxillin and phosphorylated FAK (pFAK) were detected by western blot and immunofluorescence. Integrin beta(3) exhibited stronger signals on nano-grates. pFAK and paxillin were observed as small dot-like patterns on the cell-periphery on nano-posts and as elongated and aligned patterns on nano-grates. Collectively, our observations highlighted the presence of focal (integrin beta(1), beta(3), pFAK, paxillin), fibrillar (integrin alpha(5), beta(1)) and 3-D matrix (integrin alpha(5), beta(1), paxillin) adhesions on nano-structures. The presented nano-structures offer interesting opportunities to study the interaction of cells with topographical features comparable to the size of extracellular matrix components.

    View details for DOI 10.1080/15419060701755594

    View details for Web of Science ID 000252535000002

    View details for PubMedID 18163229

  • Analysis of oxygen transport in a diffusion-limited model of engineered heart tissue BIOTECHNOLOGY AND BIOENGINEERING Brown, D. A., MacLellan, W. R., Laks, H., Dunn, J. C., Wu, B. M., Beygui, R. E. 2007; 97 (4): 962-975

    Abstract

    Cardiac tissue engineering has made notable progress in recent years with the advent of an experimental model based on neonatal cardiomyocytes entrapped in collage gels and purified basement membrane extract, known as "engineered heart tissues" (EHTs). EHTs are a formidable display of tissue-level contractile function and cellular-level differentiation, although they suffer greatly from mass transport limitations due to the high density of metabolically active cells and the diffusion-limited nature of the hydrogel. In this report, a mathematical model was developed to predict oxygen levels inside a one-dimensional, diffusion-limited model of EHT. These predictions were then compared to values measured in corresponding experiments with a hypoxia-sensitive stain (pimonidazole). EHTs were cast between two plastic discs, which allowed for mass transfer with the culture medium to occur in only the radial direction. EHTs were cultured for up to 36 h in the presence of pimonidazole, after which time they were snap-frozen, histologically sectioned, and stained for bound pimonidazole. Quantitative image analysis was performed to measure the distance from the culture medium at which hypoxia first occurs under various conditions. As tested by variation of simple design parameters, the trends in oxygen profiles predicted by the model are in reasonable agreement with those obtained experimentally, although a number of ambiguities related to the specific model parameters led to a general overprediction of oxygen concentrations. Based on the sensitivity analysis in the present study, it is concluded that diffusion-reaction models may offer relatively precise predictions of oxygen concentrations in diffusion-limited tissue constructs.

    View details for DOI 10.1002/bit.21295

    View details for Web of Science ID 000247158800029

    View details for PubMedID 17195988

  • Alcohol use in donors is a protective factor on recipients' outcome after heart transplantation TRANSPLANTATION De La Zerda, D. J., Cohen, O., Beygui, R. E., Kobashigawa, J., Hekmat, D., Laks, H. 2007; 83 (9): 1214-1218

    Abstract

    The outcome of heart transplantation is highly influenced by good donor selection. Because a history of alcoholism is prevalent among potential heart donors, we sought to explore the effect of alcohol use in donors on the outcome of heart transplantation in the recipient.A total of 437 consecutive patients underwent heart transplantation from January 2002 through September 2005. Patients' files were retrospectively studied. Mean follow-up period was 3.14+/-1.9 years (range, 3 days to 6.5 yrs). The cohort was divided into two subgroups. The alcoholic donor group (ADG) included 98 of 421 patients and the nonalcoholic donor group (NADG) included 323 of 421 patients. Mean age was 35.3+/-11.4 yrs (range, 18-66) for the ADG and 33+/-12.2 yrs (range, 18-62) for the NADG.Mortality among the ADG was 7 of 98 (7.1%) and for NADG was 55 of 323 (17.1%) (P=0.015). The mean interval time between transplant and mortality was, for ADG, 27.7+/-20.6 months (range, 0.07-51) and for NADG, 16.4+/-19.6 months (range, 0.14-73) (P=0.031). Survival rate was significantly higher among the ADG at 72.8+/-1.9 months compared with NADG at 66.2+/-1.5 months (P=0.019). Overall rejection rate was 22 of 421 (5.2%); rejection rate was 17 of 323 (5.2%) in NADG and 5 of 98 (5.1%) in ADG. Rejection free survival was 74.6+/-0.85 with no significant difference between the two groups (P=0.85).The chronic alcoholism of donors was found to be a protective factor regarding the outcome after heart transplantation. Significant differences were found in mortality rate and survival after heart transplantation between the ADG and NADG. These data support the fact that it is safe to use donors' hearts regardless of a history of alcoholism.

    View details for DOI 10.1097/01.tp.0000261713.24244.ea

    View details for Web of Science ID 000246668500013

    View details for PubMedID 17496538

  • Cell interaction with three-dimensional sharp-tip nanotopography BIOMATERIALS Choi, C., Hagvall, S. H., Wu, B. M., Dunn, J. C., Beygui, R. E., Kim, C. 2007; 28 (9): 1672-1679

    Abstract

    Cells in their native microenvironment interact with three-dimensional (3D) nanofeatures. Despite many reports on the effects of substrate nanotopography on cells, the independent effect of 3D parameters has not been investigated. Recent advances in nanofabrication for precise control of nanostructure pattern, periodicity, shape, and height enabled this systematic study of cell interactions with 3D nanotopographies. Two distinct nanopatterns (posts and grates) with varying three-dimensionalities (50-600 nm in nanostructure height) were created, while maintaining the pattern periodicity (230 nm in pitch) and tip shape (needle- or blade-like sharp tips). Human foreskin fibroblasts exhibited significantly smaller cell size and lower proliferation on needle-like nanoposts, and enhanced elongation with alignment on blade-like nanogrates. These phenomena became more pronounced as the nanotopographical three-dimensionality (structural height) increased. The nanopost and nanograte architectures provided the distinct contact guidance for both filopodia extension and the formation of adhesion molecules complex, which was believed to lead to the unique cell behaviors observed.

    View details for DOI 10.1016/j.biomaterials.2006.11.031

    View details for Web of Science ID 000244169900009

    View details for PubMedID 17174392

  • Modified reperfusion in clinical lung transplantation: The results of 100 consecutive cases JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Schnickel, G. T., Ross, D. J., Beygui, R., Shefizadeh, A., Laks, H., Saggar, R., Lynch, J. P., Ardehali, A. 2006; 131 (1): 218-223

    Abstract

    Severe primary graft dysfunction occurs in 10% to 20% of lung transplant recipients and is the leading cause of early death after lung transplantation. We hypothesized that altering the content of the initial reperfusate and maintaining a low reperfusion pressure after surgical implantation would lead to a low incidence of primary graft dysfunction.We analyzed the records of all patients who underwent lung transplantation at our institution from March 1, 2000, to August 30, 2004. The modified reperfusion technique involved the insertion of a catheter into the main or individual pulmonary artery after implantation. The recipient blood was depleted of leukocytes; supplemented with nitroglycerin; adjusted for pH and calcium level; enriched with aspartate, glutamate, and dextrose; and then administered into the pulmonary arteries of the newly transplanted lung(s) for the first 10 minutes of reperfusion. Severe primary graft dysfunction was defined as a PaO2/inspired oxygen fraction of less than 150 with diffuse infiltrate on the radiograph in absence of other causes.During this interval, 100 patients underwent lung transplantation with the modified reperfusion technique. Forty-two patients underwent single-lung transplantation, of which 5 patients required cardiopulmonary bypass for the procedure. Fifty-eight patients underwent double-lung transplantation; all double-lung transplantation procedures were performed with patients on cardiopulmonary bypass. There were no technical complications associated with the modified reperfusion. The mean PaO2/inspired oxygen fraction at 6 hours in this cohort was 252 +/- 123 mm Hg. The median number of days on the ventilator was 2. More importantly, the incidence of severe primary graft dysfunction in this cohort was 2.0%. The early survival (30-day or in-hospital mortality) of this group of patients was 97%.The technique of modified reperfusion in human lung transplantation is associated with a low incidence of severe primary graft dysfunction and favorable short-term outcomes.

    View details for DOI 10.1016/j.jtcvs.2005.08.045

    View details for Web of Science ID 000234660400033

    View details for PubMedID 16399315

  • Modulation of gene expression in neonatal rat cardiomyocytes by surface modification of polylactide-co-glycolide substrates JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A Brown, D. A., Beygui, R. E., MacLellan, W. R., Laks, H., Dunn, J. C., Wu, B. M. 2005; 74A (3): 419-429

    Abstract

    Myocardial tissue engineering presents a potential treatment option for heart disease. Cardiomyocytes isolated at various stages of development retain the ability to form contractile networks in vitro, which suggests that it should be possible to reconstitute viable myocardium given the appropriate architecture, stimuli, and cardiomyogenic cell source. This study investigates the effects of modifying substrate surface energy (by plasma etching) and protein coating (by fibronectin adsorption) on neonatal rat ventricular myocyte (NRVM) function. Primary NRVMs were cultured for 96 h on modified and control films of a common degradable polymer, polylactide-co-glycolide. Cultures were analyzed for cell spreading, protein content, and mRNA expression of atrial natriuretic factor and beta-myosin heavy chain. The results demonstrate that NRVMs cultured on etched films significantly increased in spreading, myofibril development, protein content, and gene expression of atrial natriuretic factor and beta-myosin heavy chain compared with unetched films, and that this surface energy effect is overwhelmed by the addition of fibronectin. Conclusions from this study are that surface energy and protein adsorption influence the gene expression of adherent NRVMs, and may be important for modulating the function of engineered myocardium.

    View details for DOI 10.1002/jbm.a.30344

    View details for Web of Science ID 000231179900015

  • Expression of cardiomyocytic markers on adipose tissue-derived cells in a murine model of acute myocardial injury CYTOTHERAPY Strem, B. M., Zhu, M., Alfonso, Z., Daniels, E. J., Schreiber, R., Begyui, R., MacLellan, W. R., Hedrick, M. H., Fraser, J. K. 2005; 7 (3): 282-291

    Abstract

    Animal and early clinical studies have provided evidence suggesting that intracoronary administration of autologous bone marrow-derived cells results in improved outcome following myocardial infarction. Animal studies with cultured marrow stromal cells (MSC) have provided similar data. Cells with properties that are similar to MSC have been identified in adipose tissue. Other groups have demonstrated in vivo differentiation of adipose tissue-derived cells (ADC) into cells exhibiting biochemical and functional markers of cardiac myocytes, including spontaneous beating. Based on these observations, the objective of the present study was to determine whether ADC might undergo similar differentiation in vivo in the context of myocardial injury.ADC were isolated from subcutaneous adipose tissue of Rosa26 mice (which express the beta-galactosidase transgene in almost every tissue) and injected into the intraventricular chamber of B6129S recipient mice immediately following induction of myocardial cryoinjury. Groups of recipients were euthanized at 24 hours, 7 and 14 days post surgery and examined for the presence of donor-derived cells within the heart.Beta-gal positive cells were identified in the infarcts of ADC-treated animals. No staining was observed in uninjured myocardium or in infarcts of control animals. Immunohistochemical analysis revealed co-expression of beta-gal with Myosin Heavy Chain, Nkx2.5 and with Troponin I. Co-expression of beta-galactosidase with Connexin 43, CD31, von Willebrand factor, MyoD or CD45 was not detected.Thus, these data indicate that adipose tissue contains a population of cells that has the ability to engraft injured myocardium and that this engraftment is associated with expression of cardiomyocytic markers by donor-derived cells.

    View details for DOI 10.1080/14653240510027226

    View details for Web of Science ID 000230988200010

    View details for PubMedID 16081355

  • Gelatin-embedded cell-polymer constructs for histological cryosectioning. Journal of biomedical materials research. Part B, Applied biomaterials Brown, D. A., Chou, Y. F., Beygui, R. E., Dunn, J. C., Wu, B. M. 2005; 72 (1): 79-85

    Abstract

    Many tissue-engineering strategies involve the delivery of cells via porous polymer scaffolds. Obtaining histological sections of the emerging tissue is often necessary to analyze numerous characteristics of the microscopic environment. However, difficulties arise upon applying standard histological techniques to cell-seeded polymer scaffolds. This report describes a simple and reliable method for cryosectioning cell-polymer constructs embedded in gelatin. Solvent-soluble (PLGA) and insoluble (PGA) scaffolds were cultured in vitro with preosteoblasts, followed by histological processing with paraffin, OCT, or gelatin. Although paraffin-embedded PGA scaffolds withstood standard sectioning and rinsing steps, paraffin-embedded PLGA scaffolds were partially dissolved during the clearing step. OCT-embedded scaffolds produced sections that did not adhere well to slides, and most of the sample was lost during rinsing steps. In contrast, gelatin-embedded scaffolds exhibited adequate structural integrity during cryosectioning, adhered well to the slides, retained the actual polymer morphology, and exhibited compatibility with common stains.

    View details for PubMedID 15389500

  • Repair of the symptomatic aberrant aortic arch aneurysm without hypothermic circulatory arrest. Interactive cardiovascular and thoracic surgery Beygui, R. E., Esmailian, F., Rigberg, D. A., Laks, H. 2004; 3 (4): 569-572

    Abstract

    Manifestation of anomalies of the aortic arch in adulthood has been reported in the literature. The symptoms stem from the compression of the trachea and esophagus or peripheral arterial ischemia associated with coarctation of the aberrant arch. The aberrant arch aneurysms are subject to complications of rupture or dissection. This may be the first reported case of a large complex aneurysm of an anomalous aortic arch resected on cardiopulmonary bypass without any period of hypothermic circulatory arrest or distal ischemia.

    View details for PubMedID 17670313

  • Prevention of spinal cord ischemia in an ovine model of abdominal aortic aneurysm treated with a self-expanding stent-graft JOURNAL OF ENDOVASCULAR SURGERY Beygui, R. E., Kinney, E. V., Pelc, L. R., Krievins, D., Whittemore, J., Fogarty, T. J., Zarins, C. K. 1999; 6 (3): 278-284

    Abstract

    To present novel techniques to prevent spinal ischemia during aneurysm creation and chronic bifurcated stent-graft implantation in an ovine model of abdominal aortic aneurysm (AAA).Experimental AAAs were created in 38 sheep. To prevent spinal ischemia, an internal aortic shunt was used during aneurysm creation. In the animals designated to receive bifurcated stent-grafts, a left external iliac-to-internal iliac bypass was performed to revascularize the caudal artery and prevent postdeployment spinal cord ischemia. Specimens were harvested at 1 week, 1, 3, and 6 months, and 1 year.Aneurysms were successfully created without paralysis in 35 animals. Two died due to aspiration pneumonia. Of the 33 animals implanted with endografts, 16 (94%) of 17 with straight devices and 15 (94%) of 16 with bifurcated stent-grafts survived with well-functioning, patent stent-grafts. Paralysis developed in 2 animals after endografting due to technical failures.The use of an internal shunt during aneurysm creation and internal iliac-to-external iliac transposition prior to bifurcated stent-graft deployment prevented spinal ischemia in an ovine AAA model. Chronically deployed stent-grafts were well tolerated.

    View details for Web of Science ID 000083522700011

    View details for PubMedID 10495157

  • Etiology of aortic aneurysm. Surgical technology international Zarins, C. K., Beygui, R. E. 1996; 5: 273-275

    View details for PubMedID 15858751

Conference Proceedings


  • Subclavian vein thrombosis: Outcome analysis based on etiology and modality of treatment Beygui, R. E., Olcott, C., Dalman, R. L. SPRINGER VERLAG. 1997: 247-255

    Abstract

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

    View details for Web of Science ID A1997WW54300006

    View details for PubMedID 9140599

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