Zain I Khalpey

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Courses

Scholarly Contributions

Chapters

• Khalpey, Z. I. (2016). The Translational Pathway for Mechanical Circulatory Support.. In Cardiovascular Translational Research. https://www.isctr.org/index.php/isctr-etextbook-2/.
• Khalpey, Z. I. (2014). Donation after Brain Death. In Textbook of Organ Transplantation. Wiley-Blackwell.
• Khalpey, Z. I. (2011). Endocarditis. In TSRA Review of Cardiothoracic Surgery. 1st edition(pp 190-195).
• Khalpey, Z. I. (2011). Low Cardiac Output. In TSRA Review of Cardiothoracic Surgery. 1st edition(pp 317-318).
• Khalpey, Z. I. (2011). Post Operative Care of Cardiac Surgery Patients. In Cardiac Surgery in The Adult. 4th Edition. McGraw-Hill Companies, Inc.
• Khalpey, Z. I. (2007). Postoperative Care of Cardiac Surgery Patients. In Cardiac Surgery in the Adult. McGraw-Hill.

Journals/Publications

• Avery, R., Paidy, S. R., Keller, R., Lick, S., Smith, R. G., & Khalpey, Z. (2017). Tissue Expander as a Routine Component of 50cc Total Artificial Heart Implantation for Bridge to Transplant. Circulation. Heart failure, 10(1), e003765.
• Basken, R., Bazzell, C. M., Smith, R., Janardhanan, R., & Khalpey, Z. (2017). Advantages and disadvantages of using intravenous tissue Plasminogen activator as salvage therapy for inoperable HeartWare thrombosis. Journal of cardiac surgery, 32(7), 443-446.
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  Device thrombosis is a devastating complication of left ventricular assist devices. The definitive treatment has been device exchange or explant. Evidence of increasing morbidity and mortality with device exchange has shifted strategies toward conservative management. In this report, we detail the use of thrombolytics as salvage therapy in a patient with an occlusive HeartWare ventricular assist device (HeartWare Inc., Framingham, MA) thrombus, resulting in long-term survival without further intervention.
• Ferng, A. S., Schipper, D., Connell, A. M., Marsh, K. M., Knapp, S., & Khalpey, Z. (2017). Novel vs clinical organ preservation solutions: improved cardiac mitochondrial protection. Journal of cardiothoracic surgery, 12(1), 7.
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  Heart transplantation remains the gold standard for end-stage heart failure, with current ex vivo organ storage times limited to 4 to 6 h before critical tissue damage occurs. Many preservation solutions exist in an attempt to limit both ischemic and reperfusion damage. In order to compare the effects of various storage solutions, mitochondrial function can be used to provide a sensitive analysis of cellular metabolic function.
• Khalpey, Z., Kazui, T., Ferng, A. S., Connell, A., Tran, P. L., Meyer, M., Rawashdeh, B., Smith, R. G., Sweitzer, N. K., Friedman, M., Lick, S., Slepian, M. J., & Copeland, J. G. (2017). First North American 50 cc Total Artificial Heart Experience: Conversion from a 70 cc Total Artificial Heart. ASAIO journal (American Society for Artificial Internal Organs : 1992), 62(5), e43-5.
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  The 70 cc total artificial heart (TAH) has been utilized as bridge to transplant (BTT) for biventricular failure. However, the utilization of 70 cc TAH has been limited to large patients for the low output from the pulmonary as well as systemic vein compression after chest closure. Therefore, the 50 cc TAH was developed by SynCardia (Tucson, AZ) to accommodate smaller chest cavity. We report the first TAH exchange from a 70 to 50 cc due to a fit difficulty. The patient failed to be closed with a 70 cc TAH, although the patient met the conventional 70 cc TAH fit criteria. We successfully closed the chest with a 50 cc TAH.
• Khalpey, Z., Sydow, N., Paidy, S., Slepian, M. J., Friedman, M., Cooper, A., Marsh, K. M., Schmitto, J. D., & Poston, R. (2017). Robotic-assisted implantation of ventricular assist device after sternectomy and pectoralis muscle flap. ASAIO journal (American Society for Artificial Internal Organs : 1992), 60(6), 742-3.
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  Left ventricular assist devices are increasingly important in the management of advanced heart failure. Most patients who benefit from these devices have had some prior cardiac surgery, making implantation of higher risk. This is especially true in patients who have had prior pectoralis flap reconstruction after sternectomy for mediastinitis. We outline the course of such a patient, in whom the use of robotic assistance allowed for a less invasive device implantation approach with preservation of the flap for transplantation.
• Kim, S. S., Khalpey, Z., Hsu, C., & Little, A. G. (2017). Changes in Tracheostomy- and Intubation-Related Tracheal Stenosis: Implications for Surgery. The Annals of thoracic surgery.
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  This study sought to identify the changing characteristic patterns and locations of stenosis after tracheostomy or intubation and to assess the risk factors associated with perioperative complication and restenosis after primary resection and reconstruction.
• Marsh, K. M., Ferng, A. S., Pilikian, T., Desai, A. A., Avery, R., Friedman, M., Oliva, I., Jokerst, C., Schipper, D., & Khalpey, Z. (2017). Anti-inflammatory properties of amniotic membrane patch following pericardiectomy for constrictive pericarditis. Journal of cardiothoracic surgery, 12(1), 6.
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  Since constrictive pericarditis is most often idiopathic and the pathophysiology remains largely unknown, both the diagnosis and the treatment can be challenging. However, by definition, inflammatory processes are central to this disease process. Amniotic membrane patches have been shown to possess anti-inflammatory properties and are believed to be immune privileged. Due to these properties, amniotic membrane patches were applied intraoperatively in a complicated patient presenting with constrictive pericarditis.
• Schipper, D. A., Louis, A. V., Dicken, D. S., Johnson, K., Smolenski, R. T., Black, S. M., Runyan, R., Konhilas, J., Garcia, J. G., & Khalpey, Z. (2017). Improved metabolism and redox state with a novel preservation solution: implications for donor lungs after cardiac death (DCD). Pulmonary circulation, 7(2), 494-504.
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  Lungs donated after cardiac death (DCD) are an underutilized resource for a dwindling donor lung transplant pool. Our study investigates the potential of a novel preservation solution, Somah, to better preserve statically stored DCD lungs, for an extended time period, when compared to low-potassium dextran solution (LPD). We hypothesize that Somah is a metabolically superior organ preservation solution for hypothermic statically stored porcine DCD lungs, possibly improving lung transplant outcomes. Porcine DCD lungs (n = 3 per group) were flushed with and submerged in cold preservation solution. The lungs were stored up to 12 h, and samples were taken from lung tissue and the preservation medium throughout. Metabolomic and redox potential were analyzed using high performance liquid chromatography, mass spectrometry, and RedoxSYS®, comparing substrate and pathway utilization in both preservation solutions. Glutathione reduction was seen in Somah but not in LPD during preservation. Carnitine, carnosine, and n-acetylcarnosine levels were elevated in the Somah medium compared with LPD throughout. Biopsies of Somah exposed lungs demonstrated similar trends after 2 h, up to 12 h. Adenosine gradually decreased in Somah medium over 12 h, but not in LPD. An inversely proportional increase in inosine was found in Somah. Higher oxidative stress levels were measured in LPD. Our study suggests suboptimal metabolic preservation in lungs stored in LPD. LPD had poor antioxidant potential, cytoprotection, and an insufficient redox potential. These findings may have immediate clinical implications for human organs; however, further investigation is needed to evaluate DCD lung preservation in Somah as a viable option for transplant.
• Crosby, J. R., DeCook, K. J., Tran, P. L., Betterton, E., Smith, R. G., Larson, D. F., Khalpey, Z. I., Burkhoff, D., & Slepian, M. J. (2016). A Physical Heart Failure Simulation System Utilizing the Total Artificial Heart and Modified Donovan Mock Circulation. Artificial organs.
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  With the growth and diversity of mechanical circulatory support (MCS) systems entering clinical use, a need exists for a robust mock circulation system capable of reliably emulating and reproducing physiologic as well as pathophysiologic states for use in MCS training and inter-device comparison. We report on the development of such a platform utilizing the SynCardia Total Artificial Heart and a modified Donovan Mock Circulation System, capable of being driven at normal and reduced output. With this platform, clinically relevant heart failure hemodynamics could be reliably reproduced as evidenced by elevated left atrial pressure (+112%), reduced aortic flow (-12.6%), blunted Starling-like behavior, and increased afterload sensitivity when compared with normal function. Similarly, pressure-volume relationships demonstrated enhanced sensitivity to afterload and decreased Starling-like behavior in the heart failure model. Lastly, the platform was configured to allow the easy addition of a left ventricular assist device (HeartMate II at 9600 RPM), which upon insertion resulted in improvement of hemodynamics. The present configuration has the potential to serve as a viable system for training and research, aimed at fostering safe and effective MCS device use.
• Ferng, A. S., Marsh, K. M., Fleming, J. M., Conway, R. F., Schipper, D., Bajaj, N., Connell, A. M., Pilikian, T., Johnson, K., Runyan, R., Black, S. M., Szivek, J. A., & Khalpey, Z. (2016). Adipose-derived human stem/stromal cells: comparative organ specific mitochondrial bioenergy profiles. SpringerPlus, 5(1), 2057.
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  Adipose-derived stem/stromal cells (ASCs) isolated from the stromal vascular fraction are a source of mesenchymal stem cells that have been shown to be beneficial in many regenerative medicine applications. ASCs are an attractive source of stem cells in particular, due to their lack of immunogenicity. This study examines differences between mitochondrial bioenergetic profiles of ASCs isolated from adipose tissue of five peri-organ regions: pericardial, thymic, knee, shoulder, and abdomen.
• Ferng, A. S., Marsh, K. M., Fleming, J. M., Schipper, D., Bajaj, N., Connell, A. M., Pilikan, T., Johnson, K., Runyan, R. B., Black, S. M., Szivek, J. A., & Khalpey, Z. I. (2016). Adipose-Derived Human Stem Cells: Comparative Organ Specific Mitochondrial Bioenergy Profiles. SpringerPlus, 5(2057). doi:10.1186/s40064-016-3712-1
• Ferng, A. S., Oliva, I., Jokerst, C., Avery, R., Connell, A. M., Tran, P. L., Smith, R. G., & Khalpey, Z. (2016). Translation of First North American 50 and 70 cc Total Artificial Heart Virtual and Clinical Implantations: Utility of 3D Computed Tomography to Test Fit Devices. Artificial organs.
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  Since the creation of SynCardia's 50 cc Total Artificial Hearts (TAHs), patients with irreversible biventricular failure now have two sizing options. Herein, a case series of three patients who have undergone successful 50 and 70 cc TAH implantation with complete closure of the chest cavity utilizing preoperative "virtual implantation" of different sized devices for surgical planning are presented. Computed tomography (CT) images were used for preoperative planning prior to TAH implantation. Three-dimensional (3D) reconstructions of preoperative chest CT images were generated and both 50 and 70 cc TAHs were virtually implanted into patients' thoracic cavities. During the simulation, the TAHs were projected over the native hearts in a similar position to the actual implantation, and the relationship between the devices and the atria, ventricles, chest wall, and diaphragm were assessed. The 3D reconstructed images and virtual modeling were used to simulate and determine for each patient if the 50 or 70 cc TAH would have a higher likelihood of successful implantation without complications. Subsequently, all three patients received clinical implants of the properly sized TAH based on virtual modeling, and their chest cavities were fully closed. This virtual implantation increases our confidence that the selected TAH will better fit within the thoracic cavity allowing for improved surgical outcome. Clinical implantation of the TAHs showed that our virtual modeling was an effective method for determining the correct fit and sizing of 50 and 70 cc TAHs.
• Indik, J. H., Nair, V., Rafikov, R., Nyotowidjojo, I. S., Bisla, J., Kansal, M., Parikh, D. S., Robinson, M., Desai, A., Oberoi, M., Gupta, A., Abbasi, T., Khalpey, Z., Patel, A. R., Lang, R. M., Dudley, S. C., Choi, B. R., Garcia, J. G., Machado, R. F., & Desai, A. A. (2016). Associations of Prolonged QTc in Sickle Cell Disease. PloS one, 11(10), e0164526.
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  Sudden death is a leading cause of mortality in sickle cell disease, implicating ventricular tachyarrhythmias. Prolonged QTc on an electrocardiogram (ECG), commonly seen with myocardial ischemia, is a known risk for polymorphic ventricular tachycardia (VT). We hypothesized that prolonged QTc is associated with mortality in sickle cell disease. ECG were analyzed from a cohort of 224 sickle patients (University of Illinois at Chicago, UIC) along with available laboratory, and echocardiographic findings, and from another cohort of 38 patients (University of Chicago, UC) for which cardiac MRI and free heme values were also measured. In the UIC cohort, QTc was potentially related to mortality with a hazard ratio (HR) of 1.22 per 10ms, (P = 0.015), and a HR = 3.19 (P = 0.045) for a QTc>480ms. In multivariate analyses, QTc remained significantly associated with survival after adjusting for inpatient ECG status (HR 1.26 per 10ms interval, P = 0.010) and genotype status [HR 1.21 per 10ms interval, P = 0.037). QTc trended toward association with mortality after adjusting for both LDH and hydroxyurea use (HR 1.21 per 10ms interval, P = 0.062) but was not significant after adjusting for TRV. In univariate analyses, QTc was related to markers of hemolysis including AST (P = 0.031), hemoglobin (P = 0.014), TR velocity (P = 0.036), higher in inpatients (P
• Iwanski, J., Kazui, T., Le Tran, P., Basken, R., Wong, R. K., & Khalpey, Z. (2016). Novel method using rotational thromboelastography analysis for intraoperative management of device patient with heparin-induced thrombocytopenia. Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis.
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  Heparin-induced thrombocytopenia (HIT) is a prothrombotic disease in response to previous heparin exposure. Direct thrombin inhibitors are suitable candidates for the prophylaxis of thrombosis in patients with HIT. Currently activated clotting time and activated partial thromboplastin time are used to guide dosing and monitor anticoagulation. These assays provide a measure of clot initiation and only account for a small fraction of the coagulation pathway. In this case study we performed rotational thromboelastography (ROTEM) analysis on a patient with HIT implanted with a continuous-flow CentriMag device for left ventricular support. ROTEM evaluation confirmed a decline in activated clotting time values and provided information regarding intrinsic and extrinsic clotting times. Monitoring ROTEM parameters aided in the detection of coagulopathies and the decision to administer platelet or fresh frozen plasma products. Utilizing ROTEM can guide clinical decisions in transfusions, particularly in patients with HIT, where platelet and fibrinogen levels can be safely maintained to prevent thrombosis.
• Iwanski, J., Tran, P. L., Jerman, C., Smith, R., Kazui, T., & Khalpey, Z. (2016). Off-pump left ventricular assist device exchange via re-do left mini-thoracotomy with original outflow graft preservation. Perfusion.
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  Complications associated with long-term left ventricular assist device (LVAD) use may require pump exchange due to device thrombosis or thromboembolism. Minimally invasive off-pump procedures represent an advantageous alternative to standard full sternotomy exchanges and those performed with the use of cardiopulmonary bypass. By mitigating surgical invasion and trauma to the central chest, the potential for post-operative bleeding, transfusions and complications can be reduced. This case report describes the successful off-pump exchange of a HeartWare LVAD via left re-do-thoracotomy with the re-use of the original outflow graft.
• Iwanski, J., Wong, R. K., Larson, D. F., Ferng, A. S., Runyan, R. B., Goldstein, S. A., & Khalpey, Z. I. (2016). Remodelling in an Infarcted Heart: Novel Hybrid Treatment with Transmyocardial Laser Revascularization, Surgical and Stem Cell Therapy. Springerplus, 5(1), 738. doi:DOI: 10.1186/s40064-016-2355-6
• Iwanski, J., Wong, R. K., Larson, D. F., Ferng, A. S., Runyan, R. B., Goldstein, S., & Khalpey, Z. (2016). Remodeling an infarcted heart: novel hybrid treatment with transmyocardial revascularization and stem cell therapy. SpringerPlus, 5(1), 738.
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  Transmyocardial revascularization (TMR) has emerged as an additional therapeutic option for patients suffering from diffuse coronary artery disease (CAD), providing immediate angina relief. Recent studies indicate that the volume of surgical cases being performed with TMR have been steadily rising, utilizing TMR as an adjunctive therapy. Therefore the purpose of this review is to provide an up-to-date appreciation of the current state of TMR and its future developmental directions on CAD treatment. The current potential of this therapy focuses on the implementation of stem cells, in order to create a synergistic angiogenic effect while increasing myocardial repair and regeneration. Although TMR procedures provide increased vascularization within the myocardium, patients suffering from ischemic cardiomyopathy may not benefit from angiogenesis alone. Therefore, the goal of introducing stem cells is to restore the functional state of a failing heart by providing these cells with a favorable microenvironment that will enhance stem cell engraftment.
• Kazui, T., Nicole, S., Friedman, M., Kim, S. S., Lick, S., & Khalpey, Z. I. (2016). A modified Park's stitch to correct aortic insufficiency for bioprosthetic valve at time of left ventricular assist device implant: a case report.. Journal of Cardiothoracic Surgery, 11(1), 161.
• Kazui, T., Sydow, N., Friedman, M., Kim, S., Lick, S., & Khalpey, Z. (2016). A modified Park's stitch to correct aortic insufficiency for bioprosthetic valve at time of left ventricular assist device implant: a case report. Journal of cardiothoracic surgery, 11(1), 161.
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  Aortic valve insufficiency (AI) at the time of left ventricular assist device (LVAD) insertion needs to be corrected, however there is little known about how to manage bioprosthetic valvular AI.
• Kazui, T., Tran, P. L., Echeverria, A., Jerman, C. F., Iwanski, J., Kim, S. S., Smith, R. G., & Khalpey, Z. I. (2016). Minimally invasive approach for percutaneous CentriMag right ventricular assist device support using a single PROTEKDuo Cannula. Journal of cardiothoracic surgery, 11(1), 123.
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  Right ventricular failure is a serious complication after left ventricular assist device placement.
• Keenan, J. B., Janardhanan, R., Larsen, B. T., & Khalpey, Z. (2016). Aortic valve replacement for Libman-Sacks endocarditis. BMJ case reports, 2016.
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  A 24-year-old man with systemic lupus erythematosus and antiphospholipid syndrome complicated by lupus nephritis presented with acute limb ischaemia secondary to an embolus. Following embolectomy, the patient underwent a transthoracic echocardiogram which revealed a large vegetation on all three cusps of the aortic valve. The patient was taken for an urgent aortic valve replacement with a mechanical valve. Cultures of one cusp remained sterile. Histopathological examination of the remaining two cusps revealed sterile fibrin-rich thrombotic vegetations characteristic of non-bacterial thrombotic endocarditis.
• Khalpey, Z., Bin Riaz, I., Marsh, K. M., Ansari, M. Z., Bilal, J., Cooper, A., Paidy, S., Schmitto, J. D., Smith, R., Friedman, M., Slepian, M. J., & Poston, R. (2016). Robotic Left Ventricular Assist Device Implantation Using Left Thoracotomy Approach in Patients with Previous Sternotomies. ASAIO journal (American Society for Artificial Internal Organs : 1992), 61(6), e44-6.
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  Left ventricular assist devices (LVADs) are commonly used as either a bridge-to-transplant or a destination therapy. The traditional approach for LVAD implantation is via median sternotomy, but many candidates for this procedure have a history of failed cardiac surgeries and previous sternotomy. Redo sternotomy increases the risk of heart surgery, particularly in the setting of advanced heart failure. Robotics facilitates a less invasive approach to LVAD implantation that circumvents some of the morbidity associated with a redo sternotomy. We compared the outcomes of all patients at our institution who underwent LVAD implantation via either a traditional sternotomy or using robotic assistance. The robotic cohort showed reduced resource utilization including length of hospital stay and use of blood products. As the appropriate candidates become elucidated, robotic assistance may improve the safety and cost-effectiveness of reoperative LVAD surgery.
• Khalpey, Z., Marsh, K. M., Ferng, A., Riaz, I. B., Hemphill, C., Johnson, K., Oliva, I., & Friedman, M. (2016). First in Man: Sternal Reconstruction with Autologous Stem Cells. ASAIO journal (American Society for Artificial Internal Organs : 1992), 61(5), e31-2.
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  Sternal nonunion is associated with high morbidity and treated using rigid plate and screw fixation. This is the first reported example of successful sternal reconstruction using adipose-derived stromal vascular fraction (SVF) stem cells in addition to traditional techniques. Mesenchymal stem cells, one component of the SVF, play an important role in bone healing and were therefore used to promote remedial processes in a patient with sternal nonunion. A 3D printed model of the patient's sternum was used for preoperative planning of the plating. Intraoperatively, SVF was isolated using ultrasonic cavitation and previously planned sternal plating was completed. A total of 300 million cells were delivered via both local injection and intravenously before chest closure. The patient's pain dramatically decreased, commensurate with healed areas of nonunion by 3 months and maintained at 6 months postoperatively, supported by three-dimensional computed tomography imaging. Utilizing autologous stem cells from the SVF in conjunction with existing plating techniques may provide an optimal platform to stabilize the sternum and promote bone healing, although additional study is recommended.
• Khalpey, Z., Myers, P. O., McGurk, S., Schmitto, J. D., Nauta, F., Borstlap, W., Wiegerinck, E., Wu, J., & Cohn, L. H. (2016). Nineteen-Millimeter Bioprosthetic Aortic Valves Are Safe and Effective for Elderly Patients With Aortic Stenosis. The Annals of thoracic surgery, 101(2), 650-7.
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  Replacing a stenotic aortic valve with 19-mm bioprostheses remains controversial owing to potential patient-prosthesis mismatch concerns. We report a single-center 10 year experience with 19-mm bioprosthetic valves implanted in elderly patients. We hypothesized patients would have acceptable in-hospital and long-term outcomes.
• Khalpey, Z., Smith, R., Echeverria, A., le Tran, P., & Kazui, T. (2016). A novel minimally invasive off-pump biventricular assist device insertion technique. The Journal of thoracic and cardiovascular surgery, 151(1), e5-7.
• Kim, S. S., Khalpey, Z. I., Sherry, D., Mohammed, T., & Alex, L. G. (2016). Factors in Selection and Management of Chest Tubes after Pulmonary Lobectomy: Results of a National Survey of Thoracic Surgeons. Annals of Thoracic Surgery, 101(3), 1082-1088.
• Kim, S. S., Khalpey, Z., Daugherty, S. L., Torabi, M., & Little, A. G. (2016). Factors in the Selection and Management of Chest Tubes After Pulmonary Lobectomy: Results of a National Survey of Thoracic Surgeons. The Annals of thoracic surgery, 101(3), 1082-8.
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  This study determined patterns of chest tube (CT) selection and management after open lobectomy and minimally invasive lobectomy by thoracic surgeons.
• Kutryb-Zajac, B., Yuen, A. H., Khalpey, Z., Zukowska, P., Slominska, E. M., Taylor, P. M., Goldstein, S., Heacox, A. E., Lavitrano, M., Chester, A. H., Yacoub, M. H., & Smolenski, R. T. (2016). Nucleotide Catabolism on the Surface of Aortic Valve Xenografts; Effects of Different Decellularization Strategies. Journal of cardiovascular translational research, 9(2), 119-26.
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  Extracellular nucleotide metabolism controls thrombosis and inflammation and may affect degeneration and calcification of aortic valve prostheses. We evaluated the effect of different decellularization strategies on enzyme activities involved in extracellular nucleotide metabolism. Porcine valves were tested intact or decellularized either by detergent treatment or hypotonic lysis and nuclease digestion. The rates of ATP hydrolysis, AMP hydrolysis, and adenosine deamination were estimated by incubation of aorta or valve leaflet sections with substrates followed by HPLC analysis. We demonstrated relatively high activities of ecto-enzymes on porcine valve as compared to the aortic wall. Hypotonic lysis/nuclease digestion preserved >80 % of ATP and AMP hydrolytic activity but reduced adenosine deamination to
• Lick, S. D., Tran, P. L., Kazui, T., Smith, R. G., & Khalpey, Z. I. (2016). Total Artificial Heart, Augmented by Venovenous Extracorporeal Membrane Oxygenation. ASAIO journal (American Society for Artificial Internal Organs : 1992), 62(4), e35-6.
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  Shortly after SynCardia total artificial heart (TAH) implant, venovenous extracorporeal membrane oxygenation (ECMO) via a 31 Fr Avalon cannula was used for profound hypoxic lung dysfunction. Immediately after starting ECMO, TAH flow increased by 1.5-2.0 L/min, presumably because of augmented TAH filling by the ECMO jet.
• Robinson, E. A., Khalpey, Z. I., & Janardhanan, R. (2016). A 24-year-old male with a painful and cold lower extremity. Heart (British Cardiac Society).
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  A 24-year-old male presented to the emergency department with intense pain in his right lower extremity. He has a medical history significant for systemic lupus erythematosus and antiphospholipid syndrome. He also had four prior episodes of deep venous thromboses on rivaroxaban. The patient stated that early in the morning, he started to feel intense pain that started from his knee and progressed to his calf, with associated numbness and paraesthesia. On physical examination, the limb felt cold with absent right popliteal and dorsalis pedis pulses. He was immediately taken for embolectomy after discovery of a distal common femoral artery occlusion. The patient's blood cultures remained negative. X-plane imaging on real-time three-dimensional transoesophageal echocardiography (RT-3DTEE) of the aortic valve (figure 1A) and colour Doppler (figure 1B) are shown.
• Schipper, D. A., Marsh, K. M., Ferng, A. S., Duncker, D. J., Laman, J. D., & Khalpey, Z. (2016). The Critical Role of Bioenergetics in Donor Cardiac Allograft Preservation. Journal of cardiovascular translational research, 9(3), 176-83.
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  The traditional philosophy of ex vivo organ preservation has been to limit metabolic activity by storing organs in hypothermic, static conditions. This methodology cannot provide longevity of hearts for more than 4-6 h and is thereby insufficient to expand the number of available organs. Albeit at lower rate, the breakdown of ATP still occurs during hypothermia. Furthermore, cold static preservation does not prevent the permanent damage that occurs upon reperfusion known as ischemia-reperfusion (IR) injury. This damage is caused by increased reactive oxygen species (ROS) production in combination with mitochondrial permeability transition pore (mPTP) opening, highlighting the importance of mitochondria in ischemic storage. There has recently been a major paradigm shift in the field, with emerging research supporting changes in traditional storage approaches. Novel research suggests achieving metabolic homeostasis instead of attempting to limit metabolic activity which reduces IR injury and improves graft preservation. Maintaining high ATP levels and circumventing cold organ storage would be a much more sophisticated standard for organ storage and should be the focus of future research in organ preservation. Given the link between mPTP, Ca2(+), and ROS, managing Ca2(+) influx into the mitochondria during conditioning might be the next critical step towards preventing irreversible IR injury.
• Song, S., Ayon, R. J., Yamamura, A., Yamamura, H., Dash, S., Babicheva, A., Tang, H., Sun, X., Cordery, A. G., Khalpey, Z. I., Black, S. M., Desai, A. A., Rischard, F., McDermott, K. M., Garcia, J. G., Makino, A., & Yuan, J. X. (2016). Capsaicin-induced Ca2+ Signaling is Enhanced via Upregulated TRPV1 Channels in Pulmonary Artery Smooth Muscle Cells from Patients with Idiopathic PAH. American journal of physiology. Lung cellular and molecular physiology, ajplung.00357.2016.
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  Capsaicin is an active component of chili pepper and a pain relief drug. Capsaicin can activate transient receptor potential vanilloid 1 (TRPV1) channels to increase cytosolic Ca2+ concentration ([Ca2+]cyt). A rise in [Ca2+]cyt in pulmonary artery smooth muscle cells (PASMCs) is an important stimulus for pulmonary vasoconstriction and vascular remodeling. In this study, we observed that capsaicin-induced increase in [Ca2+]cyt was significantly enhanced in PASMCs from patients with idiopathic pulmonary arterial hypertension (IPAH) compared with normal PASMCs. In addition, the protein expression level of TRPV1 in IPAH PASMCs was greater than in normal PASMCs. Increasing the temperature from 23ºC to 43ºC, or decreasing extracellular pH value from 7.4 to 5.9, enhanced capsaicin-induced increases in [Ca2+]cyt; the acidity (pH 5.9)- and heat (43ºC)-mediated enhancement of capsaicin-induced [Ca2+]cyt increases were greater in IPAH PASMCs than in normal PASMCs. Decreasing extracellular osmotic pressure from 310 to 200 mOsmol/L also increased [Ca2+]cyt and the hypoosmolarity-induced rise in [Ca2+]cyt was greater in IPAH PASMCs than in normal PASMCs. Inhibition of TRPV1 (with 5'-IRTX or capsazepine) or knockdown of TRPV1 (with shRNA) attenuated capsaicin-, acidity- and osmotic stretch-mediated [Ca2+]cyt increases in IPAH PASMCs. Capsaicin induced phosphorylation of CREB by raising [Ca2+]cyt; the capsaicin-induced CREB phosphorylation was significantly enhanced in IPAH PASMCs compared with normal PASMCs. Pharmacological inhibition and knockdown of TRPV1 attenuated IPAH PASMCs proliferation. Taken together, the capsaicin-mediated [Ca2+]cyt increase due to upregulated TRPV1 may be a critical pathogenic mechanism contributing to the augmented Ca2+ influx and excessive PASMCs proliferation in IPAH patients.
• Sweitzer, N. K., Friedman, M., Khalpey, Z. I., Lick, S., Slepian, M. J., Ferng, A. S., Kazui, T., Connell, A., Tran, P. L., Meyer, M., Rawashdeh, B., Smith, R. G., & Copeland, J. G. (2016). First North American 50 cc Total Artificial Heart Experience: Conversion from a 70 cc Total Artificial Heart. ASAIO Journal.
• Tang, H., Yamamura, A., Yamamura, H., Song, S., Fraidenburg, D. R., Chen, J., Gu, Y., Pohl, N. M., Zhou, T., Jiménez-Pérez, L., Ayon, R. J., Desai, A. A., Goltzman, D., Rischard, F., Khalpey, Z., Black, S. M., Garcia, J. G., Makino, A., & Yuan, J. X. (2016). Pathogenic role of calcium-sensing receptors in the development and progression of pulmonary hypertension. American journal of physiology. Lung cellular and molecular physiology, 310(9), L846-59.
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  An increase in cytosolic free Ca(2+) concentration ([Ca(2+)]cyt) in pulmonary arterial smooth muscle cells (PASMC) is a major trigger for pulmonary vasoconstriction and a critical stimulation for PASMC proliferation and migration. Previously, we demonstrated that expression and function of calcium sensing receptors (CaSR) in PASMC from patients with idiopathic pulmonary arterial hypertension (IPAH) and animals with experimental pulmonary hypertension (PH) were greater than in PASMC from normal subjects and control animals. However, the mechanisms by which CaSR triggers Ca(2+) influx in PASMC and the implication of CaSR in the development of PH remain elusive. Here, we report that CaSR functionally interacts with TRPC6 to regulate [Ca(2+)]cyt in PASMC. Downregulation of CaSR or TRPC6 with siRNA inhibited Ca(2+)-induced [Ca(2+)]cyt increase in IPAH-PASMC (in which CaSR is upregulated), whereas overexpression of CaSR or TRPC6 enhanced Ca(2+)-induced [Ca(2+)]cyt increase in normal PASMC (in which CaSR expression level is low). The upregulated CaSR in IPAH-PASMC was also associated with enhanced Akt phosphorylation, whereas blockade of CaSR in IPAH-PASMC attenuated cell proliferation. In in vivo experiments, deletion of the CaSR gene in mice (casr(-/-)) significantly inhibited the development and progression of experimental PH and markedly attenuated acute hypoxia-induced pulmonary vasoconstriction. These data indicate that functional interaction of upregulated CaSR and upregulated TRPC6 in PASMC from IPAH patients and animals with experimental PH may play an important role in the development and progression of sustained pulmonary vasoconstriction and pulmonary vascular remodeling. Blockade or downregulation of CaSR and/or TRPC6 with siRNA or miRNA may be a novel therapeutic strategy to develop new drugs for patients with pulmonary arterial hypertension.
• Tran, P. L., Kazui, T., Perovic, V., Mikail, P., Lick, S., Smith, R., Betterton, E. W., Venkat, R., Iwanski, J., Wong, R. K., Slepian, M. J., & Khalpey, Z. (2016). Case Report: Disparate flow in HeartMate II patient with extensive left ventricle repair. Perfusion, 31(4), 349-52.
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  This case study reports the operative management of a 63-year-old male patient following implantation of the HeartMate II (HMII) left ventricular assist device (LVAD), with a non-compliant left ventricle (LV) and a reduced right ventricular (RV) end-diastolic volume. Intraoperatively, the patient had a thin, fragile LV wall with laminated clot; a ventricular septal defect was encountered during removal of the clot. Along with an aortic valve repair, the LV and the septum were reconstructed with multiple bovine pericardium patches, thus, moderately reducing the RV and LV stroke volume. A difference in cardiac output via a Swan-Ganz catheter (approximately 1.5 l/min) was observed as opposed to the HMII's estimated flow. The result was later replicated and verified ITALIC! in vitrovia the Donovan Mock Circulation System (DMCS), where about 2 l/min lower flow on the HMII system was observed. In conclusion, the HMII flow rate displayed can be inaccurate and should only be used for trending.
• Tran, P. L., Pietropaolo, M., Valerio, L., Brengle, W., Wong, R. K., Kazui, T., Khalpey, Z. I., Redaelli, A., Sheriff, J., Bluestein, D., & Slepian, M. J. (2016). Hemolysate-mediated platelet aggregation: an additional risk mechanism contributing to thrombosis of continuous flow ventricular assist devices. Perfusion, 31(5), 401-8.
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  Despite the clinical success and growth in the utilization of continuous flow ventricular assist devices (cfVADs) for the treatment of advanced heart failure, hemolysis and thrombosis remain major limitations. Inadequate and/or ineffective anticoagulation regimens, combined with high pump speed and non-physiological flow patterns, can result in hemolysis which often is accompanied by pump thrombosis. An unexpected increase in cfVADs thrombosis was reported by multiple major VAD implanting centers in 2014, highlighting the association of hemolysis and a rise in lactate dehydrogenase (LDH) presaging thrombotic events. It is well established that thrombotic complications arise from the abnormal shear stresses generated by cfVADs. What remains unknown is the link between cfVAD-associated hemolysis and pump thrombosis. Can hemolysis of red blood cells (RBCs) contribute to platelet aggregation, thereby, facilitating prothrombotic complications in cfVADs? Herein, we examine the effect of RBC-hemolysate and selected major constituents, i.e., lactate dehydrogenase (LDH) and plasma free hemoglobin (pHb) on platelet aggregation, utilizing electrical resistance aggregometry. Our hypothesis is that elements of RBCs, released as a result of shear-mediated hemolysis, will contribute to platelet aggregation. We show that RBC hemolysate and pHb, but not LDH, are direct contributors to platelet aggregation, posing an additional risk mechanism for cfVAD thrombosis.
• Behunin, S. M., Lopez-Pier, M. A., Birch, C. L., McKee, L. A., Danilo, C., Khalpey, Z., & Konhilas, J. P. (2015). LKB1/Mo25/STRAD uniquely impacts sarcomeric contractile function and posttranslational modification. Biophysical journal, 108(6), 1484-94.
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  The myocardium undergoes extensive metabolic and energetic remodeling during the progression of cardiac disease. Central to remodeling are changes in the adenine nucleotide pool. Fluctuations in these pools can activate AMP-activated protein kinase (AMPK), the central regulator of cellular energetics. Binding of AMP to AMPK not only allosterically activates AMPK but also promotes phosphorylation of AMPK by an upstream kinase complex, LKB1/Mo25/STRAD (liver kinase B 1, mouse protein 25, STE-related adaptor protein). AMPK phosphorylation by the LKB1 complex results in a substantial increase in AMPK activity. Molecular targeting by the LKB1 complex depends on subcellular localization and transcriptional expression. Yet, little is known about the ability of the LKB1 complex to modulate targeting of AMPK after activation. Accordingly, we hypothesized that differing stoichiometric ratios of LKB1 activator complex to AMPK would uniquely impact myofilament function. Demembranated rat cardiac trabeculae were incubated with varying ratios of the LKB1 complex to AMPK or the LKB1 complex alone. After incubation, we measured the Ca(2+) sensitivity of tension, rate constant for tension redevelopment, maximum tension generation, length-dependent activation, cooperativity, and sarcomeric protein phosphorylation status. We found that the Ca(2+) sensitivity of tension and cross-bridge dynamics were dependent on the LKB1 complex/AMPK ratio. We also found that the LKB1 complex desensitizes and suppresses myofilament function independently of AMPK. A phospho-proteomic analysis of myofilament proteins revealed site-specific changes in cardiac Troponin I (cTnI) phosphorylation, as well as a unique distribution of cTnI phosphospecies that were dependent on the LKB1 complex/ AMPK ratio. Fibers treated with the LKB1 complex alone did not alter cTnI phosphorylation or phosphospecies distribution. However, LKB1 complex treatment independent of AMPK increased phosphorylation of myosin-binding protein C. Therefore, we conclude that the LKB1/AMPK signaling axis is able to alter muscle function through multiple mechanisms.
• Crosby, J. R., DeCook, K. J., Tran, P. L., Smith, R. G., Larson, D. F., Khalpey, Z. I., Burkhoff, D., & Slepian, M. J. (2015). Physiological characterization of the SynCardia total artificial heart in a mock circulation system. ASAIO journal (American Society for Artificial Internal Organs : 1992), 61(3), 274-81.
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  The SynCardia total artificial heart (TAH) has emerged as an effective, life-saving biventricular replacement system for a wide variety of patients with end-stage heart failure. Although the clinical performance of the TAH is established, modern physiological characterization, in terms of elastance behavior and pressure-volume (PV) characterization has not been defined. Herein, we examine the TAH in terms of elastance using a nonejecting left ventricle, and then characterize the PV relation of the TAH by varying preload and afterload parameters using a Donovan Mock Circulatory System. We demonstrate that the TAH does not operate with time-varying elastance, differing from the human heart. Furthermore, we show that the TAH has a PV relation behavior that also differs from that of the human heart. The TAH does exhibit Starling-like behavior, with output increasing via preload-dependent mechanisms, without reliance on an alteration of inotropic state within the operating window of the TAH. Within our testing range, the TAH is insensitive to variations in afterload; however, this insensitivity has a limit, the limit being the maximum driving pressure of the pneumatic driver. Understanding the physiology of the TAH affords insight into the functional parameters that govern artificial heart behavior providing perspective on differences compared with the human heart.
• Díaz, R., Hernandez-Vaquero, D., Khalpey, Z., & Morís, C. (2015). Mitral valve repair versus replacement for ischemic mitral regurgitation: controversy remains alive - letter 2. The Annals of thoracic surgery, 99(4), 1490.
• Khalpey, Z., Bin Riaz, I., Marsh, K. M., Ansari, M. Z., Bilal, J., Cooper, A., Paidy, S., Schmitto, J. D., Smith, R., Friedman, M., Slepian, M. J., & Poston, R. (2015). Robotic Left Ventricular Assist Device Implantation Using Left Thoracotomy Approach in Patients with Previous Sternotomies. ASAIO journal (American Society for Artificial Internal Organs : 1992), 61(6), e44-6.
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  Left ventricular assist devices (LVADs) are commonly used as either a bridge-to-transplant or a destination therapy. The traditional approach for LVAD implantation is via median sternotomy, but many candidates for this procedure have a history of failed cardiac surgeries and previous sternotomy. Redo sternotomy increases the risk of heart surgery, particularly in the setting of advanced heart failure. Robotics facilitates a less invasive approach to LVAD implantation that circumvents some of the morbidity associated with a redo sternotomy. We compared the outcomes of all patients at our institution who underwent LVAD implantation via either a traditional sternotomy or using robotic assistance. The robotic cohort showed reduced resource utilization including length of hospital stay and use of blood products. As the appropriate candidates become elucidated, robotic assistance may improve the safety and cost-effectiveness of reoperative LVAD surgery.
• Khalpey, Z., Marsh, K. M., Ferng, A., Riaz, I. B., Friedman, M., Indik, J., Avery, R., Jokerst, C., & Oliva, I. (2015). First in man: amniotic patch reduces postoperative inflammation. The American journal of medicine, 128(1), e5-6.
• Khalpey, Z., Marsh, K. M., Ferng, A., Riaz, I. B., Hemphill, C., Johnson, K., Oliva, I., & Friedman, M. (2015). First in Man: Sternal Reconstruction with Autologous Stem Cells. ASAIO journal (American Society for Artificial Internal Organs : 1992), 61(5), e31-2.
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  Sternal nonunion is associated with high morbidity and treated using rigid plate and screw fixation. This is the first reported example of successful sternal reconstruction using adipose-derived stromal vascular fraction (SVF) stem cells in addition to traditional techniques. Mesenchymal stem cells, one component of the SVF, play an important role in bone healing and were therefore used to promote remedial processes in a patient with sternal nonunion. A 3D printed model of the patient's sternum was used for preoperative planning of the plating. Intraoperatively, SVF was isolated using ultrasonic cavitation and previously planned sternal plating was completed. A total of 300 million cells were delivered via both local injection and intravenously before chest closure. The patient's pain dramatically decreased, commensurate with healed areas of nonunion by 3 months and maintained at 6 months postoperatively, supported by three-dimensional computed tomography imaging. Utilizing autologous stem cells from the SVF in conjunction with existing plating techniques may provide an optimal platform to stabilize the sternum and promote bone healing, although additional study is recommended.
• Konhilas, J. P., Chen, H., Luczak, E., McKee, L. A., Regan, J., Watson, P. A., Stauffer, B. L., Khalpey, Z. I., Mckinsey, T. A., Horn, T., LaFleur, B., & Leinwand, L. A. (2015). Diet and sex modify exercise and cardiac adaptation in the mouse. American journal of physiology. Heart and circulatory physiology, 308(2), H135-45.
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  The heart adapts to exercise stimuli in a sex-dimorphic manner when mice are fed the traditional soy-based chow. Females undergo more voluntary exercise (4 wk) than males and exhibit more cardiac hypertrophy per kilometer run (18, 32). We have found that diet plays a critical role in cage wheel exercise and cardiac adaptation to the exercise stimulus in this sex dimorphism. Specifically, feeding male mice a casein-based, soy-free diet increases daily running distance over soy-fed counterparts to equal that of females. Moreover, casein-fed males have a greater capacity to increase their cardiac mass in response to exercise compared with soy-fed males. To further explore the biochemical mechanisms for these differences, we performed a candidate-based RT-PCR screen on genes previously implicated in diet- or exercise-based cardiac hypertrophy. Of the genes screened, many exhibit significant exercise, diet, or sex effects but only transforming growth factor-β1 shows a significant three-way interaction with no genes showing a two-way interaction. Finally, we show that the expression and activity of adenosine monophosphate-activated kinase-α2 and acetyl-CoA carboxylase is dependent on exercise, diet, and sex.
• Lick, S. D., Tran, P. L., Kazui, T., Smith, R. G., & Khalpey, Z. I. (2015). Total Artificial Heart, Augmented by Venovenous Extracorporeal Membrane Oxygenation. ASAIO journal (American Society for Artificial Internal Organs : 1992), 62(4), e35-6.
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  Shortly after SynCardia total artificial heart (TAH) implant, venovenous extracorporeal membrane oxygenation (ECMO) via a 31 Fr Avalon cannula was used for profound hypoxic lung dysfunction. Immediately after starting ECMO, TAH flow increased by 1.5-2.0 L/min, presumably because of augmented TAH filling by the ECMO jet.
• Menon, N. M., Katsanis, E., Khalpey, Z., & Whitlow, P. (2015). Pediatric secondary chronic myeloid leukemia following cardiac transplantation for anthracycline-induced cardiomyopathy. Pediatric blood & cancer, 62(1), 166-8.
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  Chronic myeloid leukemia (CML) is a clonal myeloproliferative disorder of the hematopoietic stem cell that is exceptionally rare in the first five years of life, particularly as a secondary malignancy. This report describes a case of secondary CML in a four-year-old female occurring after AML treatment. Interestingly, CML developed while on immunosuppression for a heart transplant due to anthracycline-induced cardiomyopathy.
• Rafikov, R., Sun, X., Rafikova, O., Meadows, M. L., Desai, A. A., Khalpey, Z., Yuan, J. X., Fineman, J. R., & Black, S. M. (2015). Complex I dysfunction underlies the glycolytic switch in pulmonary hypertensive smooth muscle cells. Redox biology, 6, 278-86.
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  ATP is essential for cellular function and is usually produced through oxidative phosphorylation. However, mitochondrial dysfunction is now being recognized as an important contributing factor in the development cardiovascular diseases, such as pulmonary hypertension (PH). In PH there is a metabolic change from oxidative phosphorylation to mainly glycolysis for energy production. However, the mechanisms underlying this glycolytic switch are only poorly understood. In particular the role of the respiratory Complexes in the mitochondrial dysfunction associated with PH is unresolved and was the focus of our investigations. We report that smooth muscle cells isolated from the pulmonary vessels of rats with PH (PH-PASMC), induced by a single injection of monocrotaline, have attenuated mitochondrial function and enhanced glycolysis. Further, utilizing a novel live cell assay, we were able to demonstrate that the mitochondrial dysfunction in PH-PASMC correlates with deficiencies in the activities of Complexes I-III. Further, we observed that there was an increase in mitochondrial reactive oxygen species generation and mitochondrial membrane potential in the PASMC isolated from rats with PH. We further found that the defect in Complex I activity was due to a loss of Complex I assembly, although the assembly of Complexes II and III were both maintained. Thus, we conclude that loss of Complex I assembly may be involved in the switch of energy metabolism in smooth muscle cells to glycolysis and that maintaining Complex I activity may be a potential therapeutic target for the treatment of PH.
• Rana, A., Gruessner, A., Agopian, V. G., Khalpey, Z., Riaz, I. B., Kaplan, B., Halazun, K. J., Busuttil, R. W., & Gruessner, R. W. (2015). Survival benefit of solid-organ transplant in the United States. JAMA surgery, 150(3), 252-9.
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  The field of transplantation has made tremendous progress since the first successful kidney transplant in 1954.
• Rojas, S. V., Avsar, M., Hanke, J. S., Khalpey, Z., Maltais, S., Haverich, A., & Schmitto, J. D. (2015). Minimally invasive ventricular assist device surgery. Artificial organs, 39(6), 473-9.
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  The use of mechanical circulatory support to treat patients with congestive heart failure has grown enormously, recently surpassing the number of annual heart transplants worldwide. The current generation of left ventricular assist devices (LVADs), as compared with older devices, is characterized by improved technologies and reduced size. The result is that minimally invasive surgery is now possible for the implantation, explantation, and exchange of LVADs. Minimally invasive procedures improve surgical outcome; for example, they lower the rates of operative complications (such as bleeding or wound infection). The miniaturization of LVADs will continue, so that minimally invasive techniques will be used for most implantations in the future. In this article, we summarize and describe minimally invasive state-of-the-art implantation techniques, with a focus on the most common LVAD systems in adults.
• Sileshi, B., Haglund, N. A., Davis, M. E., Tricarico, N. M., Stulak, J. M., Khalpey, Z., Danter, M. R., Deegan, R., Kennedy, J., Keebler, M. E., & Maltais, S. (2015). In-hospital outcomes of a minimally invasive off-pump left thoracotomy approach using a centrifugal continuous-flow left ventricular assist device. The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation, 34(1), 107-12.
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  Minimally invasive left thoracotomy (MILT) and off-pump implantation strategies have been anecdotally reported for implantation of the HeartWare ventricular assist device (HVAD). We analyzed our experience with off-pump MILT implantation techniques and compared early in-hospital outcomes with conventional on-pump sternotomy (CS) implantation strategy.
• Sun, X., Imai, M., Nowak-Machen, M., Guckelberger, O., Enjyoji, K., Wu, Y., Khalpey, Z., Berberat, P., Munasinghe, J., & Robson, S. C. (2015). Liver damage and systemic inflammatory responses are exacerbated by the genetic deletion of CD39 in total hepatic ischemia. PURINERGIC SIGNALLING, 7(4), 427-434.
• Trey, T., Sharif, A., Singh, M. F., Khalpey, Z., & Caplan, A. L. (2015). Organ transplantation in China: concerns remain. Lancet (London, England), 385(9971), 854.
• Athanasopoulos, L. V., McGurk, S., Khalpey, Z., Rawn, J. D., Schmitto, J. D., Wollersheim, L. W., Maloney, A. M., & Cohn, L. H. (2014). Usefulness of preoperative cardiac dimensions to predict success of reverse cardiac remodeling in patients undergoing repair for mitral valve prolapse. The American journal of cardiology, 113(6), 1006-10.
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  Mitral valve repair for mitral regurgitation (MR) is currently recommended based on the degree of MR and left ventricular (LV) function. The present study examines predictors of reverse remodeling after repair for degenerative disease. We retrospectively identified 439 patients who underwent repair for myxomatous mitral valve degeneration and had both pre- and postoperative echocardiographic data available. Patients were categorized based on left atrial (LA) diameter and LV diameter standards of the American Society of Echocardiography. The outcome of interest was the degree of reverse remodeling on all heart dimensions at follow-up. Mean age was 57 ± 12 years, and 37% of patients were women. Mean preoperative LV end-diastolic diameter was 5.8 ± 0.7 cm, LV end-systolic diameter 3.5 ± 0.6 cm, LA 4.7 ± 0.7 cm, and median ejection fraction 60%. Median observation time was 81 months, and time to postoperative echocardiography was 38 months. Overall, 95% of patients had normal LV diastolic dimensions postoperatively, 93% normal LV systolic dimensions, and 37% normal LA dimensions. A Cox regression analysis showed that moderate (odds ratio [OR] 2.1, 95% confidence interval [CI] 1.3 to 3.4) or severe preoperative LA dilatation (OR 2.7, 95% CI 1.7 to 4.4), abnormal preoperative LV end-systolic dimensions (OR 1.3, 95% CI 1.1 to 1.5), and age in years (OR 1.02, 95% CI 1.01 to 1.03) were predictive of less reverse remodeling on follow-up. In conclusion, preoperative LV end-systolic dimensions and LA dilatation substantially affect the likelihood of successful LA remodeling and normalization of all heart dimensions after mitral valve repair for MR. These findings support early operation for MR before the increase in heart dimensions is nonreversible.
• Dagdeviren, C., Yang, B. D., Su, Y., Tran, P. L., Joe, P., Anderson, E., Xia, J., Doraiswamy, V., Dehdashti, B., Feng, X., Lu, B., Poston, R., Khalpey, Z., Ghaffari, R., Huang, Y., Slepian, M. J., & Rogers, J. A. (2014). Conformal piezoelectric energy harvesting and storage from motions of the heart, lung, and diaphragm. Proceedings of the National Academy of Sciences of the United States of America, 111(5), 1927-32.
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  Here, we report advanced materials and devices that enable high-efficiency mechanical-to-electrical energy conversion from the natural contractile and relaxation motions of the heart, lung, and diaphragm, demonstrated in several different animal models, each of which has organs with sizes that approach human scales. A cointegrated collection of such energy-harvesting elements with rectifiers and microbatteries provides an entire flexible system, capable of viable integration with the beating heart via medical sutures and operation with efficiencies of ∼2%. Additional experiments, computational models, and results in multilayer configurations capture the key behaviors, illuminate essential design aspects, and offer sufficient power outputs for operation of pacemakers, with or without battery assist.
• Hemphill, C., Stavoe, K., & Khalpey, Z. (2014). First in man: amniotic stem cell injection promotes scar remodeling and healing processes in late-stage fibrosis. International journal of cardiology, 174(2), 442-3.
• Hernandez-Vaquero, D., Garcia, J. M., Diaz, R., Calvo, D., Khalpey, Z., Hernández, E., Rodriguez, V., Morís, C., & Llosa, J. C. (2014). Moderate patient-prosthesis mismatch predicts cardiac events and advanced functional class in young and middle-aged patients undergoing surgery due to severe aortic stenosis. Journal of cardiac surgery, 29(2), 127-33.
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  The clinical impact of patient-prosthesis mismatch (PPM) on outcomes in young and middle-aged patients undergoing surgery for aortic valve replacement (AVR) remains unknown. Our objective was to examine the mid-term impact of PPM on overall mortality, quality of life, and cardiac events in this population.
• Khalpey, Z., Janardhanan, R., Konhilas, J., & Hemphill, C. (2014). First in Man: Adipose-derived Stromal Vascular Fraction Cells May Promote Restorative Cardiac Function. AMERICAN JOURNAL OF MEDICINE, 127(5), E11-E12.
• Khalpey, Z., Korovin, L., Chitwood, W. R., & Poston, R. (2014). Robot-assisted septal myectomy for hypertrophic cardiomyopathy with left ventricular outflow tract obstruction. The Journal of thoracic and cardiovascular surgery, 147(5), 1708-9.
• Khalpey, Z., Sydow, N., Slepian, M. J., & Poston, R. (2014). How to do it: thoracoscopic left ventricular assist device implantation using robot assistance. The Journal of thoracic and cardiovascular surgery, 147(4), 1423-5.
• Khalpey, Z., Yuen, A., Lavitrano, M., McGregor, C., Kalsi, K. K., Yacoub, M. H., & Smolenski, R. T. (2014). Mammalian mismatches in nucleotide metabolism: implications for xenotransplantation. MOLECULAR AND CELLULAR BIOCHEMISTRY, 304(1-2), 109-117.
• Poston, R., Gharagozloo, F., Khalpey, Z., & Kim, S. (2014). Robotic training in cardiothoracic surgery. The Annals of thoracic surgery, 97(1), 378.
• Rojas, S. V., Avsar, M., Khalpey, Z., Hanke, J. S., Haverich, A., & Schmitto, J. D. (2014). Minimally invasive off-pump left ventricular assist device exchange: anterolateral thoracotomy. Artificial organs, 38(7), 539-42.
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  The new generation of left ventricular assist devices has enabled minimally invasive surgical procedures. Herein we present a novel technique of left ventricular assist device exchange through a left-sided anterolateral thoracotomy.
• Tabata, M., Khalpey, Z., Aranki, S. F., Couper, G. S., Cohn, L. H., & Shekar, P. S. (2014). Minimal access surgery of ascending and proximal arch of the aorta: A 9-year experience. ANNALS OF THORACIC SURGERY, 84(1), 67-72.
• Tabata, M., Khalpey, Z., Cohn, L. H., Chen, F. Y., Bolman, R., & Rawn, J. D. (2014). Effect of preoperative statins in patients without coronary artery disease who undergo cardiac surgery. JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY, 136(6), 1510-1513.
• Takayama, H., Soni, L., Kalesan, B., Truby, L. K., Ota, T., Cedola, S., Khalpey, Z., Uriel, N., Colombo, P., Mancini, D. M., Jorde, U. P., & Naka, Y. (2014). Bridge-to-Decision Therapy With a Continuous-Flow External Ventricular Assist Device in Refractory Cardiogenic Shock of Various Causes. CIRCULATION-HEART FAILURE, 7(5), 799-806.
• Takayama, H., Soni, L., Kalesan, B., Truby, L. K., Ota, T., Cedola, S., Khalpey, Z., Uriel, N., Colombo, P., Mancini, D. M., Jorde, U. P., & Naka, Y. (2014). Bridge-to-decision therapy with a continuous-flow external ventricular assist device in refractory cardiogenic shock of various causes. Circulation. Heart failure, 7(5), 799-806.
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  Mortality for refractory cardiogenic shock remains high. In this patient cohort, there have been mixed results in mechanical circulatory support device use as a bridge-to-decision therapy. We evaluated a continuous-flow external ventricular assist device (VAD), CentriMag VAD (Thoratec Corp., Pleasanton, CA), in patients with various causes of refractory cardiogenic shock.
• Wagner, D. E., Bonenfant, N. R., Sokocevic, D., DeSarno, M. J., Borg, Z. D., Parsons, C. S., Brooks, E. M., Platz, J. J., Khalpey, Z. I., Hoganson, D. M., Deng, B., Lam, Y. W., Oldinski, R. A., Ashikaga, T., & Weiss, D. J. (2014). Three-dimensional scaffolds of acellular human and porcine lungs for high throughput studies of lung disease and regeneration. Biomaterials, 35(9), 2664-79.
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  Acellular scaffolds from complex whole organs such as lung are being increasingly studied for ex vivo organ generation and for in vitro studies of cell-extracellular matrix interactions. We have established effective methods for efficient de and recellularization of large animal and human lungs including techniques which allow multiple small segments (∼ 1-3 cm(3)) to be excised that retain 3-dimensional lung structure. Coupled with the use of a synthetic pleural coating, cells can be selectively physiologically inoculated via preserved vascular and airway conduits. Inoculated segments can be further sliced for high throughput studies. Further, we demonstrate thermography as a powerful noninvasive technique for monitoring perfusion decellularization and for evaluating preservation of vascular and airway networks following human and porcine lung decellularization. Collectively, these techniques are a significant step forward as they allow high throughput in vitro studies from a single lung or lobe in a more biologically relevant, three-dimensional acellular scaffold.
• Bartoli, C. R., Demarest, C. T., Khalpey, Z., Takayama, H., & Naka, Y. (2013). Current management of left ventricular assist device erosion. Journal of cardiac surgery, 28(6), 776-82.
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  Left ventricular assist device (LVAD) pocket infection is a serious and potentially fatal complication. Not infrequently, the device erodes externally through the thoracoabdominal wall or internally into the peritoneum. In this article, we report two cases to illustrate the presentation and challenges associated with management of LVAD-pocket infection and wound necrosis. Afterward, we review the current therapeutic strategies for LVAD erosion.
• Diaz, R., Hernandez-Vaquero, D., Llosa, J. C., & Khalpey, Z. (2013). A predictive risk model for transcatheter aortic valve procedures. An extraordinary tool but a formidable challenge. The American journal of cardiology, 111(12), 1831-2.
• Iliopoulos, D. C., Deveja, A. R., Androutsopoulou, V., Filias, V., Kastelanos, E., Satratzemis, V., Khalpey, Z., & Koudoumas, D. (2013). Single-center experience using the Freedom SOLO aortic bioprosthesis. The Journal of thoracic and cardiovascular surgery, 146(1), 96-102.
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  This study reviews a single institution experience with the Freedom SOLO (Sorin Group, Saluggia, Italy) aortic bioprosthesis.
• Khalpey, Z., Baird, C. W., & Myers, P. O. (2013). Alfieri repair for post-repair mitral systolic anterior motion in a young child. The Annals of thoracic surgery, 95(4), 1452-3.
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  An 11-year-old patient with Marfan syndrome presented with severe mitral and tricuspid regurgitation and underwent mitral valve repair consisting of a vertical folding plasty of a redundant and prolapsing A1, closure of a deep cleft-like A1-A2 indentation, and annuloplasty to 28 mm, and tricuspid valve repair. Post-bypass echocardiography showed significant systolic anterior motion of the mitral valve. The annuloplasty was upsized to 34 mm and the A1 folding plasty taken down. Echocardiography showed persistent systolic anterior motion. An edge-to-edge repair was placed at A1-P1, eliminating all systolic anterior motion. The patient had an uneventful postoperative course and 6-week follow-up.
• Myers, P. O., Khalpey, Z., Maloney, A. M., Brinster, D. R., D'Ambra, M. N., & Cohn, L. H. (2013). Edge-to-edge repair for prevention and treatment of mitral valve systolic anterior motion. The Journal of thoracic and cardiovascular surgery, 146(4), 836-40.
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  The edge-to-edge technique has been proposed to prevent systolic anterior motion (SAM) of the mitral valve. There is limited clinical data available on outcomes of this technique for this indication. We reviewed the midterm results of this technique for SAM prevention and treatment.
• Myers, P. O., del Nido, P. J., McElhinney, D. B., Khalpey, Z., Lock, J. E., & Baird, C. W. (2013). Annulus upsizing for mitral valve re-replacement in children. The Journal of thoracic and cardiovascular surgery, 146(2), 347-51.
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  Mitral valve replacement remains the last resort for treatment of congenital mitral valve disease. Enlarging the mitral annulus at the time of mitral valve replacement may allow implantation of a larger prosthesis in children.
• Neely, R. C., Davis, R. P., Stephens, E. H., Takayama, H., Khalpey, Z., Ginns, J., Lee, S. H., & Chen, J. (2013). Ventricular assist device for failing systemic ventricle in an adult with prior mustard procedure. The Annals of thoracic surgery, 96(2), 691-3.
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  The Mustard procedure is a palliative surgical procedure used to repair complete transposition of the great arteries. Cardiac transplantation remains the only definitive therapy for patients who develop heart failure after a Mustard procedure. However, pulmonary hypertension represents a major hemodynamic contraindication. The use of a ventricular assist device as destination therapy has not yet been established after a Mustard procedure. Here, we present the case of a 41-year-old patient who presented with systemic right ventricular failure following Mustard procedure complicated by pulmonary hypertension. The patient received a HeartMate II (Thoratec, Pleasanton, CA) ventricular assist device as a bridge to decision.
• Ota, T., Takayama, H., Khalpey, Z., & Naka, Y. (2013). Reinforcement of HeartMate II bend relief connection: champagne bottle technique. The Annals of thoracic surgery, 95(4), e107-8.
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  HeartMate II (Thoratec Corp, Pleasanton, CA) continuous-flow ventricular assist devices may be exchanged through a subcostal approach, where the device body can be accessed easily and safely. The existing bend relief needs to be reattached to the new device body at the end of the operation, and this reattachment often results in a malalignment between the outflow graft, the bend relief, and the device body. This causes unexpected detachment and subsequent graft kinking. We present a new, simple technique to reinforce the bend relief connection.
• Denecke, C., Reutzel-Selke, A., Sawitzki, B., Boenisch, O., Khalpey, Z., Seifert, M., Pratschke, J., Volk, H., & Tullius, S. G. (2012). Low-dose cyclosporine mediates donor hyporesponsiveness in a fully mismatched rat kidney transplant model. Transplant immunology, 26(4), 176-85.
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  Tolerance induction protocols have been successfully tested in animal models, yet their compatibility with immunosuppressive drugs remains to be fully elucidated. Our own previous data have indicated that cyclosporine A (CsA) affects the balance of effector and regulatory mechanisms with low-dose CsA doses promoting hyporesponsiveness. Here, we present a fully mismatched rat kidney model in which low-dose CsA treatment induces donor hyporesponsiveness to secondary renal allografts. Lewis recipients of DA kidney grafts received low, medium or high doses of CsA × 10 days. By 30 days, the primary transplant was removed and a second transplant of donor origin was engrafted. Following low-dose CsA, but not high-dose CsA treatment of the primary recipient, secondary transplants were accepted long-term in the absence of immunosuppression. Regulatory T-cell function was unimpaired and independent of the CyA dosage. Of note, low-dose CsA significantly reduced alloantibody titers in primary recipients. Adoptive transfer of graft infiltrating cells or splenocytes from hyporesponsive recipients supported long-term acceptance of donor kidney allografts. These results demonstrate a dose-dependent and transferable "pro-tolerogenic" effect of low-dose CsA treatment. This model is of clinical relevance to test the interference of CsA with tolerance induction in the absence of additional immunosuppression.
• Hernández-Vaquero, D., Llosa, J. C., Díaz, R., Khalpey, Z., Morales, C., Álvarez, R., López, J., & Boye, F. (2012). Impact of patient-prosthesis mismatch on 30-day outcomes in young and middle-aged patients undergoing aortic valve replacement. Journal of cardiothoracic surgery, 7, 46.
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  The impact of patient-prosthesis mismatch (PPM) on early outcomes in young and middle-aged patients undergoing conventional aortic valve replacement for severe aortic stenosis remains unknown. Our objective was to evaluate the incidence of some degree of PPM and its influence on early mortality and morbidity.
• Khalpey, Z., Bedzra, E., Stella, M. H., & Myers, P. O. (2012). Giant vein graft pseudoaneurysm with pulmonary hemorrhage. The Journal of thoracic and cardiovascular surgery, 144(2), e14-6.
• Myers, P. O., Tabata, M., Shekar, P. S., Couper, G. S., Khalpey, Z. I., & Aranki, S. F. (2012). Extensive endarterectomy and reconstruction of the left anterior descending artery: early and late outcomes. The Journal of thoracic and cardiovascular surgery, 143(6), 1336-40.
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  Coronary endarterectomy has been shown to be an effective adjunctive technique of revascularization for diffuse coronary artery disease. A long arteriotomy and reconstruction of the left anterior descending artery (LAD) are occasionally required for complete extraction of the atherosclerotic plaque. The aim of this study was to examine early and late results of this technique and compare 2 different reconstruction methods.
• Nauta, F. J., Borstlap, W. A., Stella, M., & Khalpey, Z. (2012). Cardiac tamponade: contrast reflux as an indicator of cardiac chamber equalization. Journal of cardiothoracic surgery, 7, 48.
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  Traumatic hemopericardium remains a rare entity; it does however commonly cause cardiac tamponade which remains a major cause of death in traumatic blunt cardiac injury.
• Nikolic, B., Onoe, T., Takeuchi, Y., Khalpey, Z., Primo, V., Leykin, I., Smith, R. N., & Sykes, M. (2012). Distinct Requirements for Achievement of Allotolerance Versus Reversal of Autoimmunity via Nonmyeloablative Mixed Chimerism Induction in NOD Mice. TRANSPLANTATION, 89(1), 23-32.
• Khalpey, Z., & Tullius, S. G. (2011). Refractory calciphylaxis. American journal of surgery, 202(3), e27.
• Rojas, S. V., Avsar, M., Hanke, J. S., Khalpey, Z., Maltais, S., Haverich, A., & Schmitto, J. D. (2011). Minimally Invasive Ventricular Assist Device Surgery. ARTIFICIAL ORGANS, 39(6), 473-479.
• Sun, X., Imai, M., Nowak-Machen, M., Guckelberger, O., Enjyoji, K., Wu, Y., Khalpey, Z., Berberat, P., Munasinghe, J., & Robson, S. C. (2011). Liver damage and systemic inflammatory responses are exacerbated by the genetic deletion of CD39 in total hepatic ischemia. Purinergic signalling, 7(4), 427-34.
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  Liver ischemia reperfusion injury is associated with both local damage to the hepatic vasculature and systemic inflammatory responses. CD39 is the dominant vascular endothelial cell ectonucleotidase and rapidly hydrolyses both adenosine triphosphate (ATP) and adenosine diphosphate to adenosine monophosphate. These biochemical properties, in tandem with 5'-nucleotidases, generate adenosine and potentially illicit inflammatory vascular responses and thrombosis. We have evaluated the role of CD39 in total hepatic ischemia reperfusion injury (IRI). Wildtype mice, Cd39-hemizygous mice (+/-) and matched Cd39-null mice (-/-); (n = 25 per group) underwent 45 min of total warm ischemia with full inflow occlusion necessitating partial hepatectomy. Soluble nucleoside triphosphate diphosphohydrolase (NTPDases) or adenosine/amrinone were administered to wildtype (n = 6) and Cd39-null mice (n = 6) in order to study protective effects in vivo. Parameters of liver injury, systemic inflammation, hepatic ATP determinations by P(31)-NMR and parameters of lung injury were obtained. All wildtype mice survived up to 7 days with minimal biochemical disturbances and minor evidence for injury. In contrast, 64% of Cd39+/- and 84% of Cd39-null mice required euthanasia or died within 4 h post-reperfusion with liver damage and systemic inflammation associated with hypercytokinemia. Hepatic ATP depletion was pronounced in Cd39-null mice posthepatic IRI. Soluble NTPDase or adenosine administration protected Cd39-deficient mice from acute reperfusion injury. We conclude that CD39 is protective in hepatic IRI preventing local injury and systemic inflammation in an adenosine dependent manner. Our data indicate that vascular CD39 expression has an essential protective role in hepatic IRI.
• Viswanathan, S. R., Khalpey, Z., & Ashley, S. W. (2011). Gallbladder lymphoma. Medical oncology (Northwood, London, England), 28(3), 810-2.
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  Lymphomatous involvement of the gallbladder is extremely rare. We report on a 69-year-old woman with a history of an indolent non-Hodgkin's lymphoma who was found to have a new gallbladder lesion on surveillance CT scan. The mass was resected and proved to be a follicular lymphoma with the same immunohistochemical characteristics as her original tumor 12 years prior.
• Khalpey, Z., Nehs, M. A., ElBardissi, A. W., Semel, M., & Tullius, S. G. (2010). The importance of prevention of calciphylaxis in patients who are at risk and the potential fallibility of calcimimetics in the treatment of calciphylaxis for patients with secondary hyperparathyroidism. NDT plus, 3(1), 68-70.
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  A 43-year-old African American with end-stage renal disease (ESRD) associated with membranous nephropathy and a previously failed renal transplant had received cinacalcet to treat his secondary hyperparathyroidism. Serum calcium and phosphorus levels remained within normal limits, and serum parathyroid levels had dropped significantly following treatment initiation. However, within 7 months, the patient experienced extensive necrotic bilateral medial thigh ulcers. These were biopsied and found to be a result of calciphylaxis. The patient ultimately required an urgent subtotal parathyroidectomy and recovered well with completely healed ulcers.
• Nikolic, B., Onoe, T., Takeuchi, Y., Khalpey, Z., Primo, V., Leykin, I., Smith, R. N., & Sykes, M. (2010). Distinct requirements for achievement of allotolerance versus reversal of autoimmunity via nonmyeloablative mixed chimerism induction in NOD mice. Transplantation, 89(1), 23-32.
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  Mixed hematopoietic chimerism is associated with islet allograft tolerance and may reverse autoimmunity. We developed low intensity regimens for the induction of mixed chimerism and examined the effects on autoimmunity in prediabetic nonobese diabetic (NOD) mice.
• Raichlin, E., Khalpey, Z., Kremers, W., Frantz, R. P., Rodeheffer, R. J., Clavell, A. L., Edwards, B. S., & Kushwaha, S. S. (2010). Replacement of Calcineurin-inhibitors with Sirolimus as primary immunosuppression in stable cardiac transplant recipients. TRANSPLANTATION, 84(4), 467-474.
• Rajab, T. K., Khalpey, Z., & Gallegos, R. P. (2010). Post-partum coronary artery dissection. European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery, 38(6), 806.
• Rajab, T. K., Khalpey, Z., Cohn, L. H., & Gallegos, R. P. (2010). Cardiac hemangioma presenting with angina pectoris. Journal of cardiac surgery, 25(6), 664-6.
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  A 60-year-old female presented with a two-year history of exertional chest pain and progressive dyspnea. Resection of a cardiac hemangioma arising from the area of the bifurcation of the left anterior descending and circumflex coronary arteries resulted in complete resolution of her symptoms. The symptoms were likely caused by coronary steal.
• Rajab, T. K., Khalpey, Z., Kraemer, B., Resnic, F. S., & Gallegos, R. P. (2010). Recurrent post-partum coronary artery dissection. Journal of cardiothoracic surgery, 5, 78.
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  Coronary artery dissection is a rare but well-described cause for myocardial infarction during the post-partum period. Dissection of multiple coronary arteries is even less frequent. Here we present a case of recurrent post-partum coronary artery dissections. This unusual presentation poses unique problems for management. A 35 year-old female, gravida 3 para 2, presented with myocardial infarction 9 weeks and 3 days post-partum. Cardiac catheterization demonstrated left anterior descending (LAD) dissection but an otherwise normal coronary anatomy. The lesion was treated with four everolimus eluting stents. Initially the patient made an unremarkable recovery until ventricular fibrillation arrest occurred on the following day. Unsynchronized cardioversion restored a normal sinus rhythm and repeat catheterization revealed new right coronary artery (RCA) dissection. A wire was passed distally, but it was unclear whether this was through the true or false lumen and no stents could be placed. However, improvement of distal RCA perfusion was noted on angiogram. Despite failure of interventional therapy the patient was therefore treated conservatively. Early operation after myocardial infarction has a significantly elevated risk of mortality and the initial dissection had occurred within 24 hours. This strategy proved successful as follow-up transthoracic echocardiography after four months demonstrated a preserved left ventricular ejection fraction of 55-60% without regional wall motion abnormalities. The patient remained asymptomatic from a cardiac point of view.
• Russell, E., Chien, V., Khalpey, Z., Bonaca, M., Aragam, J., Haime, M., & Crittenden, M. (2010). Left ventricular thrombosis refractory to medical therapy. Journal of the American College of Cardiology, 56(19), e37.
• Behdad, A., Sun, X., Khalpey, Z., Enjyoji, K., Wink, M., Wu, Y., Usheva, A., & Robson, S. C. (2009). Vascular smooth muscle cell expression of ectonucleotidase CD39 (ENTPD1) is required for neointimal formation in mice. Purinergic signalling, 5(3), 335-42.
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  Vascular smooth muscle cell (VSMC) migration and proliferation are critical steps in the pathogenesis of atherosclerosis, post-angioplasty restenosis, neointimal hyperplasia, and chronic allograft rejection. Extracellular nucleotides are known to influence both migration and proliferation of VSMC. Although it is well established that vascular endothelial Cd39/ENTPD1 regulates blood nucleotide concentrations, whether Cd39 associated with VSMC also impacts vascular wall pathology has not been investigated. The objective of this paper is to determine levels of expression of Cd39 on VSMC and functional consequences of gene deletion in vitro and in vivo. Cd39 is the major ectonucleotidase in VSMC, as shown by substantive decreases in ecto-ATPase and -ADPase activity in Cd39-null cells compared to wild type. Significant decreases in neointimal lesion formation are observed in Cd39-null mice at 21 days post arterial balloon injury. Stimulated Cd39-null VSMC have pronounced proliferative responses in vitro. However, using Transwell systems, we show that Cd39-null VSMC fail to migrate in response to ATP, UTP, and PDGF. Cd39 is the dominant ectonucleotidase expressed by VSMC. Deletion of Cd39 in mice results in decreased neointimal formation after vascular injury and is associated with impaired VSMC migration responses in vitro.
• Khalpey, Z., Gilfeather, M. S., Camp, P. C., & Jaklitsch, M. T. (2009). Controlled antegrade single lung reperfusion during double lung transplant. Interactive cardiovascular and thoracic surgery, 9(6), 932-3.
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  Prompt controlled reperfusion of a pulmonary allograft in a sequential double lung transplant may correct cellular ischemia prior to exposure to full hydrostatic pressures and minimize organ dysfunction. We reviewed the process of a sequential double lung transplant and describe the technique of controlled antegrade graft reperfusion of the initial implant as performed at our institution.
• Raichlin, E., Bae, J., Khalpey, Z., Edwards, B. S., Kremers, W. K., Clavell, A. L., Rodeheffer, R. J., Frantz, R. P., Rihal, C., Lerman, A., & Kushwaha, S. S. (2009). Conversion to sirolimus as primary immunosuppression attenuates the progression of allograft vasculopathy after cardiac transplantation. CIRCULATION, 116(23), 2726-2733.
• Tabata, M., Grab, J. D., Khalpey, Z., Edwards, F. H., O'Brien, S. M., Cohn, L. H., & Bolman, R. (2009). Prevalence and Variability of Internal Mammary Artery Graft Use in Contemporary Multivessel Coronary Artery Bypass Graft Surgery Analysis of the Society of Thoracic Surgeons National Cardiac Database. CIRCULATION, 120(11), 935-940.
• Tabata, M., Grab, J. D., Khalpey, Z., Edwards, F. H., O'Brien, S. M., Cohn, L. H., & Bolman, R. M. (2009). Prevalence and variability of internal mammary artery graft use in contemporary multivessel coronary artery bypass graft surgery: analysis of the Society of Thoracic Surgeons National Cardiac Database. Circulation, 120(11), 935-40.
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  Use of an internal mammary artery (IMA) is a well-recognized, nationally endorsed quality indicator for evaluating the process of operative care for coronary artery bypass graft surgery. An objective assessment of the current status of IMA use has not been systematically performed.
• Caplan, J. M., Khalpey, Z., & Gates, J. (2008). Closed traumatic head injury: dural sinus and internal jugular vein thrombosis. Emergency medicine journal : EMJ, 25(11), 777-8.
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  Dural sinus thrombosis (DST) has an annual incidence of 3-4 per million and can result from many aetiologies. Presentation of the disease can vary considerably, as can the aetiology and delay of symptoms to clinical detection. Symptoms on presentation include headache, seizures, focal neural deficits and altered mental status. There are many aetiological risk factors associated with DST, which include hypercoagulable states, oral contraceptive use, infection and mechanical causes such as cranial trauma. DST as a result of trauma is rare and aetiologies range from mechanical falls with or without skull fracture, firework explosions, gunshots to the head, blunt trauma to the head and closed head injury. Internal jugular vein thrombosis is also a rare disease and as with DST, traumatic aetiologies are uncommon. More common aetiologies include iatrogenic causes related to catheterisation as well as infectious causes (eg, Lemierre's syndrome). A case of thrombosis of the transverse sinus, sigmoid sinus and internal jugular vein associated with a closed head injury as the result of a motorcycle accident is presented.
• Franko, O. I., Khalpey, Z., & Gates, J. (2008). Brachial plexus trauma: the morbidity of hemidiaphragmatic paralysis. Emergency medicine journal : EMJ, 25(9), 614-5.
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  Phrenic nerve palsy has previously been associated with brachial plexus root avulsion; severe unilateral phrenic nerve injury is not uncommonly associated with brachial plexus injury. Brachial plexus injuries can be traumatic (gunshot wounds, lacerations, stretch/contusion and avulsion injuries) or non-traumatic in aetiology (supraclavicular brachial plexus nerve block, subclavian vein catheterisation, cardiac surgeries, or obstetric complications such as birth palsy). Despite the known association, the incidence and morbidity of a phrenic nerve injury and hemidiaphragmatic paralysis associated with traumatic brachial plexus stretch injuries remains ill-defined. The incidence of an associated phrenic nerve injury with brachial plexus trauma ranges from 10% to 20%; however, because unilateral diaphragmatic paralysis often presents without symptoms at rest, a high number of phrenic nerve injuries are likely to be overlooked in the setting of brachial plexus injury. A case report is presented of a unilateral phrenic nerve injury associated with brachial plexus stretch injury presenting with a recalcitrant left lower lobe pneumonia.
• Khalpey, Z., & Kushwaha, S. S. (2008). 'Rapping' up cardiac allograft vasculopathy. Clinical cardiology, 31(6), 286-7.
• Myers, P. O., Tabata, M., Shekar, P. S., Couper, G. S., Khalpey, Z. I., & Aranki, S. F. (2008). Extensive endarterectomy and reconstruction of the left anterior descending artery: Early and late outcomes. JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY, 143(6), 1336-1340.
• Ramos, M., Khalpey, Z., Lipsitz, S., Steinberg, J., Panizales, M. T., Zinner, M., & Rogers, S. O. (2008). Relationship of perioperative hyperglycemia and postoperative infections in patients who undergo general and vascular surgery. Annals of surgery, 248(4), 585-91.
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  Evaluate the association of perioperative hyperglycemia and postoperative infections (POI) in patients who had undergone general surgery.
• Rojas, S. V., Avsar, M., Khalpey, Z., Hanke, J. S., Haverich, A., & Schmitto, J. D. (2008). Minimally Invasive Off-Pump Left Ventricular Assist Device Exchange: Anterolateral Thoracotomy. ARTIFICIAL ORGANS, 38(7), 539-542.
• Tabata, M., Khalpey, Z., Cohn, L. H., Chen, F. Y., Bolman, R. M., & Rawn, J. D. (2008). Effect of preoperative statins in patients without coronary artery disease who undergo cardiac surgery. The Journal of thoracic and cardiovascular surgery, 136(6), 1510-3.
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  3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) have been shown to have pleiotropic effects in addition to their lipid-lowering properties. Some studies have shown the beneficial effect of preoperative statins on operative outcomes in coronary artery bypass grafting. However, the effect of preoperative statins in patients without coronary artery disease who undergo cardiac surgery remains poorly defined.
• Tabata, M., Khalpey, Z., Pirundini, P. A., Byrne, M. L., Cohn, L. H., & Rawn, J. D. (2008). Renoprotective effect of preoperative statins in coronary artery bypass grafting. AMERICAN JOURNAL OF CARDIOLOGY, 100(3), 442-444.
• Tabata, M., Khalpey, Z., Shekar, P. S., & Cohn, L. H. (2008). Reoperative minimal access aortic valve surgery: minimal mediastinal dissection and minimal injury risk. The Journal of thoracic and cardiovascular surgery, 136(6), 1564-8.
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  Minimizing surgical access in reoperative cardiac surgery allows limitation of dissection, trauma, and manipulation of patent bypass grafts. We report an 11-year experience with reoperative minimal access aortic valve surgery through an upper hemisternotomy.
• Behdad, A., Sun, X., Khalpey, Z., Enjyoji, K., Wink, M., Wu, Y., Usheva, A., & Robson, S. C. (2007). Vascular smooth muscle cell expression of ectonucleotidase CD39 (ENTPD1) is required for neointimal formation in mice. PURINERGIC SIGNALLING, 5(3), 335-342.
• Khalpey, Z., Yuen, A. H., Lavitrano, M., McGregor, C. G., Kalsi, K. K., Yacoub, M. H., & Smolenski, R. T. (2007). Mammalian mismatches in nucleotide metabolism: implications for xenotransplantation. Molecular and cellular biochemistry, 304(1-2), 109-17.
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  Acute humoral rejection (AHR) limits the clinical application of animal organs for xenotransplantation. Mammalian disparities in nucleotide metabolism may contribute significantly to the microvascular component in AHR; these, however remain ill-defined. We evaluated the extent of species-specific differences in nucleotide metabolism. HPLC analysis was performed on venous blood samples (nucleotide metabolites) and heart biopsies (purine enzymes) from wild type mice, rats, pigs, baboons, and human donors.Ecto-5'-nucleotidase (E5'N) activities were 4-fold lower in pigs and baboon hearts compared to human and mice hearts while rat activity was highest. Similar differences between pigs and humans were also observed with kidneys and endothelial cells. More than 10-fold differences were observed with other purine enzymes. AMP deaminase (AMPD) activity was exceptionally high in mice but very low in pig and baboon hearts. Adenosine deaminase (ADA) activity was highest in baboons. Adenosine kinase (AK) activity was more consistent across different species. Pig blood had the highest levels of hypoxanthine, inosine and adenine. Human blood uric acid concentration was almost 100 times higher than in other species studied. We conclude that species-specific differences in nucleotide metabolism may affect compatibility of pig organs within a human metabolic environment. Furthermore, nucleotide metabolic mismatches may affect clinical relevance of animal organ transplant models. Supplementation of deficient precursors or application of inhibitors of nucleotide metabolism (e.g., allopurinol) or transgenic upregulation of E5'N may overcome some of these differences.
• Memtsoudis, S. G., Lekowski, R. W., Rosenberger, P., Khalpey, Z., FitzGerald, D. J., Claypoole, V., Courtney, K. D., Landzberg, M. J., Bunn, H. F., & Shekar, P. S. (2007). Pulmonary thrombectomy in a patient with hemoglobin Nottingham. Perfusion, 22(4), 299-301.
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  A 36-year-old female with hemoglobin Nottingham (betaFG 5(98) Val --> Gly) causing severe hemolytic anemia and chronic thromboembolic pulmonary hypertension presented with symptomatic subacute right lower lobar pulmonary arterial thrombosis requiring surgical pulmonary thrombectomy. We describe a successful, multidisciplinary approach to the problems associated with this disease, particularly with the use of cardiopulmonary bypass and deep hypothermic circulatory arrest.
• Raichlin, E., Bae, J., Khalpey, Z., Edwards, B. S., Kremers, W. K., Clavell, A. L., Rodeheffer, R. J., Frantz, R. P., Rihal, C., Lerman, A., & Kushwaha, S. S. (2007). Conversion to sirolimus as primary immunosuppression attenuates the progression of allograft vasculopathy after cardiac transplantation. Circulation, 116(23), 2726-33.
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  We investigated the potential of conversion to sirolimus (SRL) as a primary immunosuppressant in attenuating cardiac allograft vasculopathy progression.
• Raichlin, E., Khalpey, Z., Kremers, W., Frantz, R. P., Rodeheffer, R. J., Clavell, A. L., Edwards, B. S., & Kushwaha, S. S. (2007). Replacement of calcineurin-inhibitors with sirolimus as primary immunosuppression in stable cardiac transplant recipients. Transplantation, 84(4), 467-74.
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  Calcineurin-inhibitor (CNI) nephrotoxicity is a major cause of morbidity and mortality after cardiac transplantation. The aim of this study was to assess over 2 years the safety and effect on renal function of withdrawal of CNI immunosuppression and replacement with sirolimus (SRL) in stable cardiac transplant recipients.
• Rana, A., Gruessner, A., Agopian, V. G., Khalpey, Z., Riaz, I. B., Kaplan, B., Halazun, K. J., Busuttil, R. W., & Gruessner, R. (2007). Survival Benefit of Solid-Organ Transplant in the United States. JAMA SURGERY, 150(3), 252-259.
• Shimizu, I., Hamada, T., Khalpey, Z., Miyanishi, K., & Hara, T. (2007). Ochronotic arthropathy: pathological evidence of acute destruction of the hip joint. Clinical rheumatology, 26(7), 1189-91.
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  Alcaptonuria is a hereditary disease, also known as black hip, where there is an accumulation of homogentisic acid pigmentation in joint cartilages. We describe a 74-year-old woman who showed acute destruction of her left hip joint. She received a total hip arthroplasty on her right side in July 2000, and was diagnosed with ochronosis. Her postoperative follow-up was at our institutions outpatient department. She first complained of increasing groin pain in July 2005, after which she had a left total hip arthroplasty in October 2005. Histopathologically, samples from this patient showed "fragmentation and cleft formation" in the cartilage of the femoral head. In addition, the samples revealed a remarkable degradation of proteoglycan, which is the secondary most abundant constituent of extra cellular matrix. These findings suggested that "cleft formation", where cracks develop toward the center, caused an acute destructive arthropathy with morphological fragility suggestive of ochronosis.
• Tabata, M., Khalpey, Z., Aranki, S. F., Couper, G. S., Cohn, L. H., & Shekar, P. S. (2007). Minimal access surgery of ascending and proximal arch of the aorta: a 9-year experience. The Annals of thoracic surgery, 84(1), 67-72.
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  Minimal access approaches are becoming readily accepted techniques for cardiac valve surgery. However, the safety or benefit of this approach for aortic surgery has not been well investigated.
• Tabata, M., Khalpey, Z., Pirundini, P. A., Byrne, M. L., Cohn, L. H., & Rawn, J. D. (2007). Renoprotective effect of preoperative statins in coronary artery bypass grafting. The American journal of cardiology, 100(3), 442-4.
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  The renoprotective effect of preoperative statin use in coronary artery bypass grafting remains poorly defined. A retrospective review of 1,802 consecutive patients who underwent isolated coronary artery bypass grafting from January 2002 to October 2005 was performed. Of those, 1,039 patients were receiving statins preoperatively, and 763 patients were not. Two propensity score-matched cohorts each of 641 patients (statin and nonstatin groups) were constructed. Multivariate logistic regression analyses for matched patients and all patients were performed to investigate whether preoperative statin use was associated with the incidence of new renal insufficiency. In a matched analysis, the statin group had a lower incidence of new renal insufficiency than the nonstatin group (1.6% vs 3.9%, odds ratio 0.39, 95% confidential interval 0.18 to 0.82, p = 0.01). Multivariate logistic regression analysis including all patients also showed that preoperative statin use (odds ratio 0.54, 95% confidence interval 0.30 to 0.99, p = 0.047) was significantly associated with low incidence of new postoperative renal insufficiency. In conclusion, preoperative statin use may be renoprotective after coronary artery bypass grafting.
• Tabata, M., Khalpey, Z., Shekar, P. S., & Cohn, L. H. (2007). Reoperative minimal access aortic valve surgery: Minimal mediastinal dissection and minimal injury risk. JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY, 136(6), 1564-1568.
• Tabata, M., Umakanthan, R., Khalpey, Z., Aranki, S. F., Couper, G. S., Cohn, L. H., & Shekar, P. S. (2007). Conversion to full sternotomy during minimal-access cardiac surgery: Reasons and results during a 9.5-year experience. JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY, 134(1), 165-169.
• Tabata, M., Umakanthan, R., Khalpey, Z., Aranki, S. F., Couper, G. S., Cohn, L. H., & Shekar, P. S. (2007). Conversion to full sternotomy during minimal-access cardiac surgery: reasons and results during a 9.5-year experience. The Journal of thoracic and cardiovascular surgery, 134(1), 165-9.
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  A hemisternotomy approach to minimal-access cardiac surgery is associated with a faster postoperative recovery because of reduced postoperative pain and improved respiratory function. Conversion to a full sternotomy is occasionally required for reasons that remain inadequately reported.
• Wagner, D. E., Bonenfant, N. R., Sokocevic, D., DeSarno, M. J., Borg, Z. D., Parsons, C. S., Brooks, E. M., Platz, J. J., Khalpey, Z. I., Hoganson, D. M., Deng, B., Lam, Y. W., Oldinski, R. A., Ashikaga, T., & Weiss, D. J. (2007). Three-dimensional scaffolds of acellular human and porcine lungs for high throughput studies of lung disease and regeneration. BIOMATERIALS, 35(9), 2664-2679.
• Smolenski, R. T., Khalpey, Z., Osborne, F. N., Yuen, A., Slominska, E. M., Lipiński, M., Lavitrano, M., Rose, M., & Yacoub, M. H. (2006). Species differences of endothelial extracellular nucleotide metabolism and its implications for xenotransplantation. Pharmacological reports : PR, 58 Suppl, 118-25.
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  There is a severe shortage of human organs available for transplantation and xenotransplantation - use of animal organs has long been suggested to overcome this problem. Recent advances in understanding rejection in xenotranplantation and development of genetically engineered pigs that reduced hyperacute rejection were fundamental steps forward but other unresolved mechanisms remain an obstacle. Endothelium is a major target for all rejection mechanisms in xenotransplantation. This is caused not only by location of these cells at the first line of contact but also because endothelium is a very variable cell type across different species. This variability affects not only its immune characteristics but also physiology and metabolism. Nucleotide metabolism is particularly variable in endothelial cells of different species. We attributed particular importance to one such difference - much lower activity of ecto-5'-nucleotidase (E5'N) in pig endothelial cells as compared to human. To study its significance our group developed pig endothelial cell line stably expressing human E5'N. This allowed us to determine that E5'N controls the rate of adenosine formation from extracellular nucleotides even with ATP as the substrate. Expression of human E5'N in pig cells attenuated several mechanisms involved in xenotransplant rejection such as cytotoxicity induced by human NK cells, human platelet aggregation or human platelet adherence to endothelium. We conclude that species differences of endothelial nucleotide metabolism could contribute to rejection following xenotransplantation. These studies suggests that expression of human ecto-5'-nucleotidase in pigs genetically engineered for xenotransplantation could help to prolong graft survival.
• Yuen, A. H., Khalpey, Z., Lavitrano, M., McGregor, C. G., Kalsi, K. K., Yacoub, M. H., & Smolenski, R. T. (2006). Differences in activities of the enzymes of nucleotide metabolism and its implications for cardiac xenotransplantation. Nucleosides, nucleotides & nucleic acids, 25(9-11), 1221-4.
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  Xenotransplantation is one be possible solution for a severe shortage of human organs available for transplantation. However, only a few studies addressed metabolic compatibility of transplanted animal organs. Our aim was to compare activities of adenosine metabolizing enzymes in the heart of different species that are relevant to clinical or experimental xenotransplantation. We noted fundamental differences: ecto-5' nucleotidease (E5' N) activity was 4-fold lower in pig and baboon hearts compared to the human hearts while mouse activity was compatible with human and rat activity was three times higher than human. There also were significant differences in AMP-deaminase (AMPD), adenosine deaminase (ADA) and purine nucleoside phosphorylase (PNP) activities. We conclude that differences in nucleotide metabolism may contribute to organ dysfunction after xenotransplantation.
• Khalpey, Z., Yuen, A. H., Kalsi, K. K., Kochan, Z., Karbowska, J., Slominska, E. M., Forni, M., Macherini, M., Bacci, M. L., Batten, P., Lavitrano, M., Yacoub, M. H., & Smolenski, R. T. (2005). Loss of ecto-5'nucleotidase from porcine endothelial cells after exposure to human blood: Implications for xenotransplantation. Biochimica et biophysica acta, 1741(1-2), 191-8.
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  The endothelial cell surface expression of ecto-5'-nucleotidase (E5'N, CD73) is thought to be essential for the extracellular formation of cytoprotective, anti-thrombotic and immunosuppressive adenosine. Decreased E5'N activity may play a role in xenograft acute vascular rejection, preventing accommodation and tolerance mechanisms. We investigated the extent of changes in E5'N activity and other enzymes of purine metabolism in porcine hearts or endothelial cells when exposed to human blood or plasma and studied the role of humoral immunity in this context. Pig hearts, wild type (WT, n = 6) and transgenic (T, n = 5) for human decay accelerating factor (hDAF), were perfused ex vivo with fresh human blood for 4 h. Pig aortic endothelial cells (PAEC) were exposed for 3 h to autologous porcine plasma (PP), normal (NHP) or heat inactivated human plasma (HHP), with and without C1-inhibitor. Enzyme activities were measured in heart or endothelial cell homogenates with an HPLC based procedure. The baseline activity of E5'N in WT and T porcine hearts were 6.60 +/- 0.33 nmol/min/mg protein and 8.54 +/- 2.10 nmol/min/mg protein respectively (P < 0.01). Ex vivo perfusion of pig hearts with fresh human blood for 4 h resulted in a decrease in E5'N activity to 4.01 +/- 0.32 and 4.52 +/- 0.52 nmol/min/mg protein (P < 0.001) in WT and T hearts respectively, despite attenuation of hyperacute rejection in transgenic pigs. The initial PAEC activity of E5'N was 9.10 +/- 1.40 nmol/min/mg protein. Activity decreased to 6.76 +/- 0.57 and 4.58 +/- 0.47 nmol/min/mg protein (P < 0.01) after 3 h exposure of HHP and NHP respectively (P < 0.05), whereas it remained unchanged at 9.62 +/- 0.88 nmol/min/mg protein when incubated with PP controls. C1-inhibitor partially preserved E5'N activity, similar to the effect of HHP. Adenosine deaminase, adenosine kinase and AMP deaminase (other enzymes of purine metabolism) showed a downward trend in activity, but none were statistically significant. We demonstrate a specific decrease in E5'N activity in pig hearts following exposure to human blood which impairs adenosine production resulting in a loss of a cytoprotective phenotype, contributing to xenograft rejection. This effect is triggered by human humoral immune responses, and complement contributes but does not fully mediate E5'N depletion.
• Kushwaha, S. S., Khalpey, Z., Frantz, R. P., Rodeheffer, R. J., Clavell, A. L., Daly, R. C., McGregor, C. G., & Edwards, B. S. (2005). Sirolimus in cardiac transplantation: use as a primary immunosuppressant in calcineurin inhibitor-induced nephrotoxicity. The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation, 24(12), 2129-36.
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  Calcineurin inhibitor (CNI) immunosuppressants are a major cause of renal dysfunction in cardiac transplant recipients, leading to increased morbidity and mortality. The aim of this study was to evaluate the efficacy and safety of CNI withdrawal and substitution with sirolimus as the primary immunosuppressant, and assess the effect on renal function in cardiac transplant recipients with CNI-induced renal impairment.
• Lim, E., Ali, A., Khalpey, Z., Ashrafian, H., Jackson, C., Ali, Z., Chamageorgakis, T., Wells, F., Pepper, J., Desouza, A., & Moat, N. (2005). A validated simple model to predict coexistent coronary disease in patients undergoing mitral valve surgery. The Journal of thoracic and cardiovascular surgery, 129(6), 1318-21.
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  The primary limitation of the American Heart Association/American College of Cardiology guidelines is specificity. To improve the selection process, we proposed a simple additive model including age (1 point for every 5 years above 50), male sex (2 points), hypercholesterolemia (2 points), angina (3 points), and electrocardiographic evidence of ischemia (3 points). We recommend screening angiography at 3 or more points. This model was previously derived from 359 patients at Papworth Hospital.
• Smolenski, R. T., Khalpey, Z., Yuen, A. C., Dziewit, H., Slominska, E. M., Borkowski, T., Zdunek, M., Kochan, Z., Karbowska, J., Lavitrano, M., & Yacoub, M. H. (2005). Purine metabolism in pigs and humans and its implications for xenotransplantation. Nucleosides, nucleotides & nucleic acids, 24(4), 263-6.
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  We compared concentrations of nucleotide substrates and activities of enzymes of nucleotide metabolism in pig and human blood, heart, and kidney. The most important difference was lower ecto-5-nucleotidase (ESN) activity in both pig hearts and kidney. Furthermore, higher hypoxanthine, inosine, adenine, and uracil, but lower uridine and uric acid concentrations were observed in pig blood as compared to human. A twofold increase in UTP concentration has been observed in pig hearts following 4 h perfusion with human blood. Purine metabolism is an important target for genetic and pharmacological manipulation during xenotransplantations.
• Khalpey, Z., & Lim, E. (2004). Cardiothoracic training in the United Kingdom. BMJ (Clinical research ed.), 328(7430), s3-4.
• Khalpey, Z., Koch, C. A., & Platt, J. L. (2004). Xenograft transplantation. Anesthesiology clinics of North America, 22(4), 871-85.
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  Interest in xenotransplantation has increased because conventional organ transplantation has been limited by a shortage of human organs. Although xenotransplantation could alleviate the existing and anticipated need for tissues and organs, the application is hindered by various biologic obstacles. This article reviews the basis for the demand for xenotransplantation, the obstacles to clinical application, and potential approaches to overcoming those obstacles.
• Koch, C. A., Khalpey, Z. I., & Platt, J. L. (2004). Accommodation: preventing injury in transplantation and disease. Journal of immunology (Baltimore, Md. : 1950), 172(9), 5143-8.
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  Humoral immunity, as a cause of damage to blood vessels, poses a major barrier to successful transplantation of organs. Under some conditions, humoral immunity causes little or no damage to an organ graft. We have referred to this condition, in which a vascularized graft functions in the face of humoral immunity directed against it, as "accommodation." In this paper, we review changes in the graft and in the host that may account for accommodation, and we consider that what we call accommodation of organ grafts may occur widely in the context of immune responses, enabling immune responses to target infectious organisms without harming self-tissues.
• Wu, X., Khalpey, Z., & Cascalho, M. (2004). Cellular physiology of mismatch repair. Current pharmaceutical design, 10(32), 4121-6.
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  The DNA mismatch repair system maintains genomic stability by correcting DNA sequence errors generated during DNA replication, during genetic exchanges between chromosomes i.e., recombination, and by correcting DNA lesions caused by mutagenic agents such as cis-platinum. Post-synthesis mismatch repair improves almost 1000-fold the fidelity of DNA replication; however, the functions of mismatch repair proteins extend well beyond DNA repair. Recent studies suggest that mismatch repair is part of the machinery that couples DNA damage and repair to cell cycle regulation and apoptosis. These studies indicate that tolerance to certain DNA lesions (such as methylation and cis-platinum adducts) is associated with inefficient activation of cell cycle checkpoints and inefficient activation of apoptosis in mismatch repair deficient cells. Hence, mismatch repair proteins regulate the survival threshold to DNA damage, and this function provides a novel platform for understanding the role of mismatch repair in B cells, in tumor formation, as well as in resistance to chemotherapy. In this communication, we review how mismatch repair may contribute to the physiology of cells and may be regulated by the intracellular trafficking of mismatch repair proteins.
• Ali, A., Lim, E., Halstead, J., Ashrafian, H., Ali, Z., Khalpey, Z., Theodorou, P., Chamageorgakis, T., Kumar, P., Jackson, C., & Pepper, J. (2003). Porcine or human stentless valves for aortic valve replacement? Results of a 10-year comparative study. The Journal of heart valve disease, 12(4), 430-5; discussion 435.
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  Stentless porcine valves in the aortic position exhibit similar excellent hemodynamic performance to homografts, but have the advantage of availability. Their performance was compared over a 10-year period in a single-surgeon and single-institution series.
• Khalpey, Z. (2002). Service from the heart--lessons from Mozambique. MedGenMed : Medscape general medicine, 4(1), 4.
• Wickramasinghe, S. N., Hasan, R., & Khalpey, Z. (1996). Differences in the serum levels of acetaldehyde and cytotoxic acetaldehyde-albumin complexes after the consumption of red and white wine: in vitro effects of flavonoids, vitamin E, and other dietary antioxidants on cytotoxic complexes. Alcoholism, clinical and experimental research, 20(5), 799-803.
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  After the consumption of ethanol, acetaldehyde levels increase in the serum, and the serum develops a nondialyzable cytotoxic activity caused by the formation of unstable acetaldehyde-albumin complexes. The concentration of acetaldehyde in the serum and the cytotoxic activity in serum albumin 8.5 hr after six healthy volunteers began to drink 94 g of ethanol were significantly less when the ethanol was consumed as red wine than as white wine. The serum acetaldehyde was measured by a fluorigenic HPLC assay, and the cytotoxic activity in albumin was determined using two different assays based on dissimilar endpoints: (1) detachment of adherent A9 cells and (2) impairment of the ability of A9 cells to reduce tetrazolium. When serum obtained from five other healthy volunteers after the consumption of white wine was incubated at 37 degrees C for 3 hr with a number of dietary antioxidants at a concentration of 100 mumol/liter, the cytotoxicity of the albumin was markedly reduced. The antioxidants studied consisted of six flavonoids (kaempherol, fisetin, quercetin catechin, taxifolin, and coumarin) and three nonflavonoids (salicylic acid, tannic acid, and alpha-tocopherol). In the cases of alpha-tocopherol, a statistically significant reduction of cytotoxicity was observed at a concentration of 10 mumol/liter. In addition, the cytotoxicity of artificially prepared acetaldehyde-albumin complexes was significantly reduced when such complexes were incubated with 50 to 100 mumol/liter of kaempherol, fisetin, quercetin, coumarin or salicylic acid, or 10 mumol/liter of alpha-tocopherol at 37 degrees C for 3 hr. Evidently, in vitro, flavonoid and nonflavonoid dietary constituents reduce the amount of unstable acetaldehyde-albumin complexes found in both postalcohol serum and in artificially produced acetaldehyde-albumin complexes. The difference in the amount of unstable acetaldehyde-albumin complexes found in serum after the consumption of red and white wine may therefore be caused by the higher concentration of antioxidants, including flavonoids, in red wine than in white wine. Because acetaldehyde and acetaldehyde-albumin complexes have been implicated in the pathogenesis of alcohol-mediated tissue damage, these data suggest that dietary antioxidants may influence the biological consequences of excess alcohol consumption.

Presentations

• Khalpey, Z. I. (2016, January). Stem cell and liquid matrix therapy in advanced heart failure patients with mechanical circulatory support. 2016 Cell Therapy & Regenerative Medicine Symposium “Tomorrow’s Cures Today”. UA COM Tucson.
• Kim, S. S., Khalpey, Z. I., & Alex, L. G. (2016, November). Changes in Tracheostomy and Intubation Related Tracheal Stenosis: Implications for Surgery. Southern Thoracic Surgical Association 63rd Annual Meeting. Naples, Florida: Southern Thoracic Surgical Association.
• Kevin, D., C, J., Avery, R. J., Khalpey, Z. I., Oliva, I. B., Kazui, T., & Desai, V. (2015, Novemeber). The Total Artificial Heart: Historical Perspectives, Current Applications, Future Directions. RSNA 101st Scientific Assembly and Annual Meeting. Chicago, Illinois: Radiologic Society of North America.
• Khalpey, Z. I. (2013, April). Lung Bioscaffolds: comparative lung decellularization techniques. Experimental Biology AAA annual meeting. Boston, MA.
• Khalpey, Z. I. (2008, February). Perioperative glycemic control in noncardiac surgical patients: Does it reduce postoperative infections?. Annual Academic Surgical Contress. Hyatt Regency Huntington Beach Resort & Spa in Huntington Beach, CA.

Poster Presentations

• Khalpey, Z. I. (2015, April). Analyzing the metabolic microenvironment of co-cultured stem cells and cardiomyocytes. American Society for Biochemistry and Molecular Biology (ASBMB) 2015 annual meeting. Boston, MA.
• Khalpey, Z. I. (2015, April). Inoperative management of device patient with HIT using ROTEM analysis. American Society of Extracorporeal Technology. 53rd International Meeting. Tampa, FL.
• Khalpey, Z. I. (2015, April). Mitochondrial transfer to myocytes from fibroblasts or stem cells is both rapid and substantial. 22nd Weinstein Cardiovascular Developmental Conference. Boston, MA.
• Khalpey, Z. I. (2015, April). The use of three factor prothrombin complex concentrate to reverse warfarin treated mechanical circulatory device patients immediately prior to heart transplant. SHLT 35th annual meeting. Nice, France.
• Khalpey, Z. I. (2015, July). Bioenergetics of human cardiomyocytes and amniotic fluid stem cells. 30th Annual National MD/PhD Student Conference. Keystone, Colorado.
• Khalpey, Z. I. (2015, March). Amniotic stem cells as donors of bioenergy in the heart. 2015 Keystone Symposia Conference. Copper Mountain, CO.
• Khalpey, Z. I. (2015, March). Transmyocardial laser revascularization and the use of surgical and/or cell therapy to remodel an infarcted heart. American Academy of Cardiovascular Perfusion annual meeting. Phoenix, AZ.
• Khalpey, Z. I. (2015, September). Comparative metabolism of patients with heart failure and mechanical circulatory devices. 22nd annual congress of the ISRBP. San Francisco, CA.
• Khalpey, Z. I. (2014, April). Clinical Grade Human Lung Decellularization: A Rapid, Novel Technique. AATS annual meeting. Toronto, ON, Canada. Toronto, ON, Canada.
• Khalpey, Z. I. (2014, April). Extended preservation of lungs at subnormothermia with a novel organ storage solution “Somah”: salvage, reconditioning and functional evaluation. ISHLT 34th annual meeting. San Deigo, CA.
• Khalpey, Z. I. (2014, April). Robotic implantation of left ventricular assist devices: a new era in cardiac surgery. ISHLT 34th annual meeting. San Deigo, CA.
• Khalpey, Z. I. (2014, January). Establishing a novel protocol for lung bioscaffold cryopreservation using a porcine model. STS 50th annual meeting. Orlando, FL.
• Khalpey, Z. I. (2014, May). Influence of experience on mental stress during Robotic cardiac surgery. ISMICS annual meeting. Boston, MA.
• Janardhanan, R., Lotun, K., Khalpey, Z. I., Smith, M. C., Rutter, T., Nemanova, D., & Friedman, M. (2013, June). MITRAL VALVE OBSTRUCTION: ACCURATE DIAGNOSIS BY 3D-TRANSESOPHAGEAL ECHOCARDIOGRAPHY. AMERICAN SOCIETY OF ECHOCARDIOGRAPHY. Minneapolis, MN.
• Khalpey, Z. I. (2013, December). Maintaining architecture and compliance of cryopreserved lung bioscaffolds. Pulmonary Fibrosis Foundation annual meeting. La Jolla, CA.
• Khalpey, Z. I. (2013, November). Assessing stress during robotic cardiac surgery-comparison between simulated surgery, actual surgery, and surgery supervision cases. Society of Robotic Surgery annual meeting. Orlando, FL.
• Khalpey, Z. I. (2013, November). Effect of a novel ORCA bioreactor on an intact porcine heart decellularization. American Heart Association annual meeting. Dallas, TX.
• Khalpey, Z. I. (2013, November). Optimization of porcine heart decellularization. American College of Physicians: Arizona chapter scientific meeting.. Tucson, AZ.
• Khalpey, Z. I. (2013, October). Bioprinting a three dimensional cardiac patch: A novel model for stem cell delivery in chronic heart failure. 2013 Medical Student Program of the American College of Surgeons. Washington DC.
• Khalpey, Z. I. (2013, October). Development of a porcine lung decellularization protocol by utilizing a novel ORCA bioreactor. STSA 60th Annual meeting. Scottsdale, AZ.
• Khalpey, Z. I. (2013, September). Device thrombogenicity emulation (DTE) assisted VAD design improvement is associated with reduced platelet activation in vivo. 21st Congress of the International Society for Rotary Blood Pumps. Yokohama, Japan.
• Khalpey, Z. I. (2013, September). Robotic implantation of VADs: The next step forward. 21st Congress of the International Society for Rotary Blood Pumps. Yokohama, Japan.
• Khalpey, Z. I. (2012, September). Lung Organogenesis: pneumospheres, bioscaffolds and 3D bioreactors. 10th Annual AMA research symposium. Honolulu, HI.
• Khalpey, Z. I. (2008, February). Developments of the Surgical research portal (SRP): synergizing NSQIP Data Acquisition with electronic medical records efficiency. Annual Academic Surgical Congress. Huntington Beach, CA.
• Khalpey, Z. I. (2006, June). Reoperative Minimally Invasive AVR following previous CABG: a comparative outcome study. EACTS.
• Khalpey, Z. I. (2006, November). Tolerance to islet allografts and reversal of autoimmunity achieved via mixed allogeneic chimerism. Levine Diabetes Symposium. Boston, MA.
• Khalpey, Z. I. (2005, February). Adenosine Metabolism: Species differences and role of humoral immunity in xenograft cytoprotection. MRS / Academy / RCP Clinical Scientists in Training meeting.
• Khalpey, Z. I. (2005, February). Species-specific metabolic differences in cardiac xenotransplantation models. Royal Society of Medicine. Northwick Park Hospital/St Marks Hospital, London.
• Khalpey, Z. I. (2005, May). Comparison of nucleotide metabolism in different species relevant to xenotransplantation. American Transplant Congress. Seattle, WA.
• Khalpey, Z. I. (2005, October). Blood Transfusion in cardiac surgery: Does Packed Red Blood Cell Transfusion Affect Renal Function. AATS.
• Khalpey, Z. I. (2005, October). Immune Tolerance Induction: From Bench to Bedside. Levine Diabetes Symposium.
• Khalpey, Z. I. (2005, October). Minimally invasive ascending aortic and arch surgery surgery: Early and Late outcomes. AATS.
• Khalpey, Z. I. (2005, October). Sirolimus in Cardiac Transplantation: Use as a Primary Immunosuppressant in Calcineurin-Inhibitor induced Nephrotoxicity. ISHLT 26th International Meeting and Scientific Symposium. Madrid, Spain.
• Khalpey, Z. I. (2005, October). Surgical Treatment of Primary Cardiac Tumors. AATS.
• Khalpey, Z. I. (2004, April). Xenotransplantation: A New Darwinian Vantage?. ISHLT. San Francisco, CA.