The Experts below are selected from a list of 3525 Experts worldwide ranked by ideXlab platform
Robert J. Porte - One of the best experts on this subject based on the ideXlab platform.
-
Subnormothermic Machine Perfusion of Steatotic Livers Results in Increased Energy Charge at the Cost of Anti-Oxidant Capacity Compared to Normothermic Perfusion.
Metabolites, 2019Co-Authors: Negin Karimian, Korkut Uygun, Robert J. Porte, Siavash Raigani, Viola Huang, Sonal Nagpal, Ehab O A Hafiz, Irene Beijert, Paria Mahboub, Martin L. YarmushAbstract:There continues to be significant debate regarding the most effective mode of ex situ Machine Perfusion of livers for transplantation. Subnormothermic (SNMP) and normothermic Machine Perfusion (NMP) are two methods with different benefits. We examined the metabolomic profiles of discarded steatotic human livers during three hours of subnormothermic or normothermic Machine Perfusion. Steatotic livers regenerate higher stores of ATP during SNMP than NMP. However, there is a significant depletion of available glutathione during SNMP, likely due to an inability to overcome the high energy threshold needed to synthesize glutathione. This highlights the increased oxidative stress apparent in steatotic livers. Rescue of discarded steatotic livers with Machine Perfusion may require the optimization of redox status through repletion or supplementation of reducing agents.
-
First report of successful transplantation of a pediatric donor liver graft after hypothermic Machine Perfusion.
Pediatric transplantation, 2019Co-Authors: Maureen J M Werner, Otto B. Van Leeuwen, Iris E M De Jong, Frank A.j.a. Bodewes, Masato Fujiyoshi, Olaf C. Luhker, Rene Scheenstra, Yvonne De Vries, Ruben H J De Kleine, Robert J. PorteAbstract:One of the main limiting factors in pediatric liver transplantation is donor availability. For adults, DCD liver grafts are increasingly used to expand the donor pool. To improve outcome after DCD liver transplantation, ex situ Machine Perfusion is used as an alternative organ preservation strategy, with the supplemental value of providing oxygen to the graft during preservation. We here report the first successful transplantation of a pediatric DCD liver graft after hypothermic oxygenated Machine Perfusion. The full-size liver graft was derived from a 13-year-old, female DCD donor and was end-ischemic pretreated with dual hypothermic oxygenated Machine Perfusion. Arterial and portal pressures were set at 18 and 4 mm Hg, slightly lower than protocolized settings for adult livers. During 2 hours of Machine Perfusion, portal and arterial flows increased from 100 to 210 mL/min and 30 to 63 mL/min, respectively. The pretreated liver graft was implanted in a 16-year-old girl with progressive familial intrahepatic cholestasis type 2. Postoperative AST, ALT, and prothrombin time normalized within a week. The recipient quickly recovered and was discharged from the hospital after 18 days. One year after transplantation, she is in excellent condition with a completely normal liver function and histology. This case is the first report of successful transplantation of a pediatric DCD liver graft after hypothermic oxygenated Machine Perfusion and illustrates the potential role of ex situ Machine Perfusion in expanding the donor pool and improving outcome after pediatric liver transplantation.
-
Metabolic profiling during ex vivo Machine Perfusion of the human liver
Scientific reports, 2016Co-Authors: Bote G. Bruinsma, Robert J. Porte, James H. Avruch, Pepijn D. Weeder, Gautham V. Sridharan, Nima Saeidi, Sinan Ozer, Sharon Geerts, Michal Heger, Thomas M. Van GulikAbstract:As donor organ shortages persist, functional Machine Perfusion is under investigation to improve preservation of the donor liver. The transplantation of donation after circulatory death (DCD) livers is limited by poor outcomes, but its application may be expanded by ex vivo repair and assessment of the organ before transplantation. Here we employed subnormothermic (21 °C) Machine Perfusion of discarded human livers combined with metabolomics to gain insight into metabolic recovery during Machine Perfusion. Improvements in energetic cofactors and redox shifts were observed, as well as reversal of ischemia-induced alterations in selected pathways, including lactate metabolism and increased TCA cycle intermediates. We next evaluated whether DCD livers with steatotic and severe ischemic injury could be discriminated from ‘transplantable’ DCD livers. Metabolomic profiling was able to cluster livers with similar metabolic patterns based on the degree of injury. Moreover, Perfusion parameters combined with differences in metabolic factors suggest variable mechanisms that result in poor energy recovery in injured livers. We conclude that Machine Perfusion combined with metabolomics has significant potential as a clinical instrument for the assessment of preserved livers.
-
Ex Situ Normothermic Machine Perfusion of Donor Livers.
Journal of visualized experiments : JoVE, 2015Co-Authors: Negin Karimian, Henri G D Leuvenink, Alix P M Matton, Andrie C. Westerkamp, Laura C. Burlage, Sanna Op Den Dries, Ton Lisman, Korkut Uygun, James F. Markmann, Robert J. PorteAbstract:In contrast to conventional static cold preservation (0-4 °C), ex situ Machine Perfusion may provide better preservation of donor livers. Continuous Perfusion of organs provides the opportunity to improve organ quality and allows ex situ viability assessment of donor livers prior to transplantation. This video article provides a step by step protocol for ex situ normothermic Machine Perfusion (37 °C) of human donor livers using a device that provides a pressure and temperature controlled pulsatile Perfusion of the hepatic artery and continuous Perfusion of the portal vein. The Perfusion fluid is oxygenated by two hollow fiber membrane oxygenators and the temperature can be regulated between 10 °C and 37 °C. During Perfusion, the metabolic activity of the liver as well as the degree of injury can be assessed by biochemical analysis of samples taken from the Perfusion fluid. Machine Perfusion is a very promising tool to increase the number of livers that are suitable for transplantation.
-
Functional Human Liver Preservation and Recovery by Means of Subnormothermic Machine Perfusion
Journal of visualized experiments : JoVE, 2015Co-Authors: Bote G. Bruinsma, Negin Karimian, James F. Markmann, Robert J. Porte, James H. Avruch, Pepijn D. Weeder, Gautham V. Sridharan, Basak E. Uygun, Heidi Yeh, Korkut UygunAbstract:There is currently a severe shortage of liver grafts available for transplantation. Novel organ preservation techniques are needed to expand the pool of donor livers. Machine Perfusion of donor liver grafts is an alternative to traditional cold storage of livers and holds much promise as a modality to expand the donor organ pool. We have recently described the potential benefit of subnormothermic Machine Perfusion of human livers. Machine perfused livers showed improving function and restoration of tissue ATP levels. Additionally, Machine Perfusion of liver grafts at subnormothermic temperatures allows for objective assessment of the functionality and suitability of a liver for transplantation. In these ways a great many livers that were previously discarded due to their suboptimal quality can be rescued via the restorative effects of Machine Perfusion and utilized for transplantation. Here we describe this technique of subnormothermic Machine Perfusion in detail. Human liver grafts allocated for research are perfused via the hepatic artery and portal vein with an acellular oxygenated perfusate at 21 °C.
Bote G. Bruinsma - One of the best experts on this subject based on the ideXlab platform.
-
Metabolic profiling during ex vivo Machine Perfusion of the human liver
Scientific reports, 2016Co-Authors: Bote G. Bruinsma, Robert J. Porte, James H. Avruch, Pepijn D. Weeder, Gautham V. Sridharan, Nima Saeidi, Sinan Ozer, Sharon Geerts, Michal Heger, Thomas M. Van GulikAbstract:As donor organ shortages persist, functional Machine Perfusion is under investigation to improve preservation of the donor liver. The transplantation of donation after circulatory death (DCD) livers is limited by poor outcomes, but its application may be expanded by ex vivo repair and assessment of the organ before transplantation. Here we employed subnormothermic (21 °C) Machine Perfusion of discarded human livers combined with metabolomics to gain insight into metabolic recovery during Machine Perfusion. Improvements in energetic cofactors and redox shifts were observed, as well as reversal of ischemia-induced alterations in selected pathways, including lactate metabolism and increased TCA cycle intermediates. We next evaluated whether DCD livers with steatotic and severe ischemic injury could be discriminated from ‘transplantable’ DCD livers. Metabolomic profiling was able to cluster livers with similar metabolic patterns based on the degree of injury. Moreover, Perfusion parameters combined with differences in metabolic factors suggest variable mechanisms that result in poor energy recovery in injured livers. We conclude that Machine Perfusion combined with metabolomics has significant potential as a clinical instrument for the assessment of preserved livers.
-
Functional Human Liver Preservation and Recovery by Means of Subnormothermic Machine Perfusion
Journal of visualized experiments : JoVE, 2015Co-Authors: Bote G. Bruinsma, Negin Karimian, James F. Markmann, Robert J. Porte, James H. Avruch, Pepijn D. Weeder, Gautham V. Sridharan, Basak E. Uygun, Heidi Yeh, Korkut UygunAbstract:There is currently a severe shortage of liver grafts available for transplantation. Novel organ preservation techniques are needed to expand the pool of donor livers. Machine Perfusion of donor liver grafts is an alternative to traditional cold storage of livers and holds much promise as a modality to expand the donor organ pool. We have recently described the potential benefit of subnormothermic Machine Perfusion of human livers. Machine perfused livers showed improving function and restoration of tissue ATP levels. Additionally, Machine Perfusion of liver grafts at subnormothermic temperatures allows for objective assessment of the functionality and suitability of a liver for transplantation. In these ways a great many livers that were previously discarded due to their suboptimal quality can be rescued via the restorative effects of Machine Perfusion and utilized for transplantation. Here we describe this technique of subnormothermic Machine Perfusion in detail. Human liver grafts allocated for research are perfused via the hepatic artery and portal vein with an acellular oxygenated perfusate at 21 °C.
-
subnormothermic Machine Perfusion for ex vivo preservation and recovery of the human liver for transplantation
American Journal of Transplantation, 2014Co-Authors: Bote G. Bruinsma, Heidi Yeh, Tim A. Berendsen, Nima Saeidi, Sinan Ozer, Op Den S Dries, Paulo N Martins, Adam Farmer, R N SmithAbstract:To reduce widespread shortages, attempts are made to use more marginal livers for transplantation. Many of these grafts are discarded for fear of inferior survival rates or biliary complications. Recent advances in organ preservation have shown that ex vivo subnormothermic Machine Perfusion has the potential to improve preservation and recover marginal livers pretransplantation. To determine the feasibility in human livers, we assessed the effect of 3 h of oxygenated subnormothermic Machine Perfusion (21°C) on seven livers discarded for transplantation. Biochemical and microscopic assessment revealed minimal injury sustained during Perfusion. Improved oxygen uptake (1.30 [1.11-1.94] to 6.74 [4.15-8.16] mL O2 /min kg liver), lactate levels (4.04 [3.70-5.99] to 2.29 [1.20-3.43] mmol/L) and adenosine triphosphate content (45.0 [70.6-87.5] pmol/mg prePerfusion to 167.5 [151.5-237.2] pmol/mg after Perfusion) were observed. Liver function, reflected by urea, albumin and bile production, was seen during Perfusion. Bile production increased and the composition of bile (bile salts/phospholipid ratio, pH and bicarbonate concentration) became more favorable. In conclusion, ex vivo subnormothermic Machine Perfusion effectively maintains liver function with minimal injury and sustains or improves various hepatobiliary parameters postischemia.
Korkut Uygun - One of the best experts on this subject based on the ideXlab platform.
-
viability testing of discarded livers with normothermic Machine Perfusion alleviating the organ shortage outweighs the cost
Clinical Transplantation, 2020Co-Authors: Korkut Uygun, Siavash Raigani, Reinier J De Vries, Cailah Carroll, Yawen Chen, David C Chang, Stuti ShroffAbstract:BACKGROUND Over 700 donor livers are discarded annually in the United States due to high risk of poor graft function. The objective of this study was to determine the impact of using normothermic Machine Perfusion to identify transplantable livers among those currently discarded. STUDY DESIGN A series of 21 discarded human livers underwent viability assessment during normothermic Machine Perfusion. Cross-sectional analysis of the Scientific Registry of Transplant Recipients database and cost analysis was performed to extrapolate the case series to national experience. RESULTS 21 discarded human livers were included in the Perfusion cohort. 11 of 20 (55%) eligible grafts met viability criteria for transplantation. Grafts in the Perfusion cohort had a similar donor risk index compared to discarded grafts (n=1402) outside of New England in 2017 and 2018 (median [IQR]: 2.0 [1.5, 2.4] vs. 2.0 [1.7, 2.3], P=0.40). 705 (IQR 677-741) livers were discarded annually in the United States since 2005, translating to the potential for 398 additional transplants nationally. The median cost to identify a transplantable graft with Machine Perfusion was $28,099 USD. CONCLUSIONS Normothermic Machine Perfusion of discarded livers could identify a significant number of transplantable grafts, significantly improving access to liver transplantation.
-
Moving the Margins: Updates on the Renaissance in Machine Perfusion for Organ Transplantation
Current Transplantation Reports, 2020Co-Authors: Cray V. Noah, Korkut Uygun, Siavash Raigani, Philipp Tratnig-frankl, Curtis L. Cetrulo, Heidi YehAbstract:Escalating end-organ disease coupled with stagnant donor pools has begotten global organ shortages. Ex vivo organ Perfusion, used briefly in the early days of clinical transplant and then sidelined for decades by static cold storage, has resurged to address this organ paucity. Given the recent prolific application of Machine Perfusion as a platform for assessment, preservation, and treatment of marginal grafts, this review summarizes salient results from the past 2–3 years in kidney, liver, lung, heart, pancreas, vascularized composite allograft, and xenograft transplantation. Clinical trials have established the ability of ex vivo Perfusion to make previously declined thoracic and abdominal organs transplantable without sacrificing short- or long-term function and survival. In addition to extended assessment and superior preservation, Machine Perfusion enables targeted delivery of cutting-edge gene and immunomodulatory therapies. At the leading edge, ex vivo Perfusion has recently led to breakthroughs in xenotransplantation, enabled ischemia-free liver transplants, and been incorporated into out-of-hospital organ resuscitation centers. Ex vivo Machine Perfusion is transitioning from being dormant to indispensable in clinical organ transplantation. Providing a platform for extended assessment, superior preservation, and targeted therapy, ex vivo organ Perfusion can make marginal, previously declined organs a part of the donor pool. Pioneering pre-clinical studies continue to provide guidance on how to optimize and leverage this invaluable system for further expansion of lifesaving organ transplantation.
-
Moving the Margins: Updates on the Renaissance in Machine Perfusion for Organ Transplantation
Current Transplantation Reports, 2020Co-Authors: Cray V. Noah, Siavash Raigani, Philipp Tratnig-frankl, Curtis L. Cetrulo, Korkut UygunAbstract:Purpose of Review Escalating end-organ disease coupled with stagnant donor pools has begotten global organ shortages. Ex vivo organ Perfusion, used briefly in the early days of clinical transplant and then sidelined for decades by static cold storage, has resurged to address this organ paucity. Given the recent prolific application of Machine Perfusion as a platform for assessment, preservation, and treatment of marginal grafts, this review summarizes salient results from the past 2–3 years in kidney, liver, lung, heart, pancreas, vascularized composite allograft, and xenograft transplantation. Recent Findings Clinical trials have established the ability of ex vivo Perfusion to make previously declined thoracic and abdominal organs transplantable without sacrificing short- or long-term function and survival. In addition to extended assessment and superior preservation, Machine Perfusion enables targeted delivery of cutting-edge gene and immunomodulatory therapies. At the leading edge, ex vivo Perfusion has recently led to breakthroughs in xenotransplantation, enabled ischemia-free liver transplants, and been incorporated into out-of-hospital organ resuscitation centers. Summary Ex vivo Machine Perfusion is transitioning from being dormant to indispensable in clinical organ transplantation. Providing a platform for extended assessment, superior preservation, and targeted therapy, ex vivo organ Perfusion can make marginal, previously declined organs a part of the donor pool. Pioneering pre-clinical studies continue to provide guidance on how to optimize and leverage this invaluable system for further expansion of lifesaving organ transplantation.
-
Subnormothermic Machine Perfusion of Steatotic Livers Results in Increased Energy Charge at the Cost of Anti-Oxidant Capacity Compared to Normothermic Perfusion.
Metabolites, 2019Co-Authors: Negin Karimian, Korkut Uygun, Robert J. Porte, Siavash Raigani, Viola Huang, Sonal Nagpal, Ehab O A Hafiz, Irene Beijert, Paria Mahboub, Martin L. YarmushAbstract:There continues to be significant debate regarding the most effective mode of ex situ Machine Perfusion of livers for transplantation. Subnormothermic (SNMP) and normothermic Machine Perfusion (NMP) are two methods with different benefits. We examined the metabolomic profiles of discarded steatotic human livers during three hours of subnormothermic or normothermic Machine Perfusion. Steatotic livers regenerate higher stores of ATP during SNMP than NMP. However, there is a significant depletion of available glutathione during SNMP, likely due to an inability to overcome the high energy threshold needed to synthesize glutathione. This highlights the increased oxidative stress apparent in steatotic livers. Rescue of discarded steatotic livers with Machine Perfusion may require the optimization of redox status through repletion or supplementation of reducing agents.
-
Ex Situ Normothermic Machine Perfusion of Donor Livers.
Journal of visualized experiments : JoVE, 2015Co-Authors: Negin Karimian, Henri G D Leuvenink, Alix P M Matton, Andrie C. Westerkamp, Laura C. Burlage, Sanna Op Den Dries, Ton Lisman, Korkut Uygun, James F. Markmann, Robert J. PorteAbstract:In contrast to conventional static cold preservation (0-4 °C), ex situ Machine Perfusion may provide better preservation of donor livers. Continuous Perfusion of organs provides the opportunity to improve organ quality and allows ex situ viability assessment of donor livers prior to transplantation. This video article provides a step by step protocol for ex situ normothermic Machine Perfusion (37 °C) of human donor livers using a device that provides a pressure and temperature controlled pulsatile Perfusion of the hepatic artery and continuous Perfusion of the portal vein. The Perfusion fluid is oxygenated by two hollow fiber membrane oxygenators and the temperature can be regulated between 10 °C and 37 °C. During Perfusion, the metabolic activity of the liver as well as the degree of injury can be assessed by biochemical analysis of samples taken from the Perfusion fluid. Machine Perfusion is a very promising tool to increase the number of livers that are suitable for transplantation.
Heidi Yeh - One of the best experts on this subject based on the ideXlab platform.
-
Moving the Margins: Updates on the Renaissance in Machine Perfusion for Organ Transplantation
Current Transplantation Reports, 2020Co-Authors: Cray V. Noah, Korkut Uygun, Siavash Raigani, Philipp Tratnig-frankl, Curtis L. Cetrulo, Heidi YehAbstract:Escalating end-organ disease coupled with stagnant donor pools has begotten global organ shortages. Ex vivo organ Perfusion, used briefly in the early days of clinical transplant and then sidelined for decades by static cold storage, has resurged to address this organ paucity. Given the recent prolific application of Machine Perfusion as a platform for assessment, preservation, and treatment of marginal grafts, this review summarizes salient results from the past 2–3 years in kidney, liver, lung, heart, pancreas, vascularized composite allograft, and xenograft transplantation. Clinical trials have established the ability of ex vivo Perfusion to make previously declined thoracic and abdominal organs transplantable without sacrificing short- or long-term function and survival. In addition to extended assessment and superior preservation, Machine Perfusion enables targeted delivery of cutting-edge gene and immunomodulatory therapies. At the leading edge, ex vivo Perfusion has recently led to breakthroughs in xenotransplantation, enabled ischemia-free liver transplants, and been incorporated into out-of-hospital organ resuscitation centers. Ex vivo Machine Perfusion is transitioning from being dormant to indispensable in clinical organ transplantation. Providing a platform for extended assessment, superior preservation, and targeted therapy, ex vivo organ Perfusion can make marginal, previously declined organs a part of the donor pool. Pioneering pre-clinical studies continue to provide guidance on how to optimize and leverage this invaluable system for further expansion of lifesaving organ transplantation.
-
Opportunities for Therapeutic Intervention During Machine Perfusion.
Current transplantation reports, 2017Co-Authors: Negin Karimian, Heidi YehAbstract:Purpose of Review There is a vast discrepancy between the number of patients waiting for organ transplantation and the available donor organs. Ex situ Machine Perfusion (MP) has emerged in an effort to expand the donor pool, by improving organ preservation, providing diagnostic information, and more recently, acting as a platform for organ improvement. This article reviews the current status of MP with a focus on its role in organ pre-conditioning and therapeutic interventions prior to transplantation.
-
Functional Human Liver Preservation and Recovery by Means of Subnormothermic Machine Perfusion
Journal of visualized experiments : JoVE, 2015Co-Authors: Bote G. Bruinsma, Negin Karimian, James F. Markmann, Robert J. Porte, James H. Avruch, Pepijn D. Weeder, Gautham V. Sridharan, Basak E. Uygun, Heidi Yeh, Korkut UygunAbstract:There is currently a severe shortage of liver grafts available for transplantation. Novel organ preservation techniques are needed to expand the pool of donor livers. Machine Perfusion of donor liver grafts is an alternative to traditional cold storage of livers and holds much promise as a modality to expand the donor organ pool. We have recently described the potential benefit of subnormothermic Machine Perfusion of human livers. Machine perfused livers showed improving function and restoration of tissue ATP levels. Additionally, Machine Perfusion of liver grafts at subnormothermic temperatures allows for objective assessment of the functionality and suitability of a liver for transplantation. In these ways a great many livers that were previously discarded due to their suboptimal quality can be rescued via the restorative effects of Machine Perfusion and utilized for transplantation. Here we describe this technique of subnormothermic Machine Perfusion in detail. Human liver grafts allocated for research are perfused via the hepatic artery and portal vein with an acellular oxygenated perfusate at 21 °C.
-
subnormothermic Machine Perfusion for ex vivo preservation and recovery of the human liver for transplantation
American Journal of Transplantation, 2014Co-Authors: Bote G. Bruinsma, Heidi Yeh, Tim A. Berendsen, Nima Saeidi, Sinan Ozer, Op Den S Dries, Paulo N Martins, Adam Farmer, R N SmithAbstract:To reduce widespread shortages, attempts are made to use more marginal livers for transplantation. Many of these grafts are discarded for fear of inferior survival rates or biliary complications. Recent advances in organ preservation have shown that ex vivo subnormothermic Machine Perfusion has the potential to improve preservation and recover marginal livers pretransplantation. To determine the feasibility in human livers, we assessed the effect of 3 h of oxygenated subnormothermic Machine Perfusion (21°C) on seven livers discarded for transplantation. Biochemical and microscopic assessment revealed minimal injury sustained during Perfusion. Improved oxygen uptake (1.30 [1.11-1.94] to 6.74 [4.15-8.16] mL O2 /min kg liver), lactate levels (4.04 [3.70-5.99] to 2.29 [1.20-3.43] mmol/L) and adenosine triphosphate content (45.0 [70.6-87.5] pmol/mg prePerfusion to 167.5 [151.5-237.2] pmol/mg after Perfusion) were observed. Liver function, reflected by urea, albumin and bile production, was seen during Perfusion. Bile production increased and the composition of bile (bile salts/phospholipid ratio, pH and bicarbonate concentration) became more favorable. In conclusion, ex vivo subnormothermic Machine Perfusion effectively maintains liver function with minimal injury and sustains or improves various hepatobiliary parameters postischemia.
Matthias Peltz - One of the best experts on this subject based on the ideXlab platform.
-
Successful transplantation in canines after long-term coronary sinus Machine Perfusion preservation of donor hearts
The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation, 2016Co-Authors: S.m. Brant, M.l. Cobert, Michael E. Jessen, C. Holmes, La Shondra Powell, John M. Shelton, Matthias PeltzAbstract:Background Machine Perfusion is a promising strategy for donor heart preservation, but delivery of perfusate through the aorta may be limited by aortic valve incompetence. We hypothesized that retrograde Machine Perfusion preservation through the coronary sinus avoided this issue and allowed for recovery of donor hearts after long-term storage. Methods Canine hearts were procured after arrest with 1 liter University of Wisconsin Machine Perfusion Solution (UWMPS) and preserved for 14 hours by static hypothermic storage (Static group, n = 5) or retrograde Machine Perfusion through the coronary sinus (RP group, n = 5). Myocardial oxygen consumption (MVo 2 ) and lactate were monitored in perfused hearts. Hearts were implanted and reperfused for 6 hours. The pre-load recruitable stroke work was determined as a measure of myocardial function. Cardiac enzyme release was quantified. Cell death was evaluated by TUNEL (terminal deoxynucleotidyltransferase-mediated deoxy uridine triphosphate nick-end label). Results MVo 2 decreased initially then stabilized. Lactate accumulation was low in RP hearts. All RP hearts separated from cardiopulmonary bypass. All Static hearts required a return to bypass ( p p p Conclusions Retrograde Machine Perfusion can preserve donor hearts for long intervals. Cardiac function after implantation suggested excellent myocardial protection. Retrograde Machine Perfusion appears promising for extending the donor ischemic interval and improving results of heart transplantation.
-
Effects of antegrade and retrograde Machine Perfusion preservation on cardiac function after transplantation in canines.
Transplantation proceedings, 2014Co-Authors: S.m. Brant, M.l. Cobert, L.m. West, Michael E. Jessen, David H. Rosenbaum, Matthias PeltzAbstract:Abstract Introduction Most studies investigating Machine Perfusion preservation for heart transplantation perfuse through the aortic root (antegrade), but the coronary sinus (retrograde) is a potential option. We hypothesized that retrograde Machine Perfusion provides better functional protection than static storage, while avoiding the potential irregular Perfusion seen when aortic insufficiency occurs with antegrade Perfusion. Materials and Methods Eighteen canine donor hearts were arrested, procured, and stored in modified Celsior solution for 4 hours by using either static storage at 0°C to 4°C (n = 6) or Machine Perfusion preservation at 5°C via the aortic root (antegrade, n = 6) or coronary sinus (retrograde, n = 6). Lactate and myocardial oxygen consumption were measured in perfused hearts. Hearts were reimplanted and reperfused for 6 hours with hourly function calculated by using the preload recruitable stroke work (PRSW) relation. Myocardial water content was determined at the end of the experiment. Results Storage lactate levels and myocardial oxygen consumption were comparable in both perfused groups. The PRSW was increased immediately after bypass in the antegrade group (120.6 ± 19.1 mm Hg) compared with the retrograde (75.0 ± 11.3 mm Hg) and static (78.1 ± 10.5 mm Hg) storage groups ( P P Conclusions Both antegrade and retrograde Perfusion demonstrated excellent functional preservation, at least equivalent to static storage. Initial function was superior in the antegrade group, but the retrograde hearts displayed better function late after rePerfusion. Neither perfused group developed significant edema. Machine Perfusion preservation is a promising technique for improving results of cardiac transplantation.
-
Retrograde Machine Perfusion for Long-Term Preservation of Canine Hearts
The Journal of Heart and Lung Transplantation, 2013Co-Authors: M.l. Cobert, S.m. Brant, L.m. West, Michael E. Jessen, Matthias PeltzAbstract:Purpose Most Machine Perfusion preservation strategies utilize antegrade delivery of perfusate or blood through the ascending aorta but this technique is potentially limited by aortic valve incompetence. We hypothesize that retrograde Machine Perfusion preservation through the coronary sinus avoids this issue and allows for recovery of donor hearts after long-term storage. Methods and Materials Canine hearts were procured after cardioplegic arrest with 1 liter University of Wisconsin Machine Perfusion Solution (UWMPS) and preserved for 12 hours in UWMPS by either conventional static storage (Static group, n=4) at 0-4oC or retrograde Machine Perfusion through the coronary sinus (RP group, n=4) at 5oC. Myocardial oxygen consumption (MVO 2 ) and lactate accumulation were monitored in perfused hearts. Donor hearts were implanted into recipient animals and reperfused for six hours. The preload recruitable stroke work (PRSW) was determined hourly. Total CK was measured at the end of each experiment. Results RP hearts maintained stable MVO 2 over the 12 hour preservation interval. Lactate accumulation was low in RP hearts. All RP hearts separated from cardiopulmonary bypass (CPB). All static storage hearts either did not separate from CPB or required a return to CPB by the end of the six hour rePerfusion interval (p Conclusions Retrograde Machine Perfusion can preserve donor hearts for long intervals. Cardiac function after implantation was not different from baseline function suggesting excellent myocardial protection. A retrograde Machine Perfusion strategy appears promising for safely extending the donor ischemic interval and improving results of heart transplantation. GroupTotal Ischemic Time (min)PRSW (mm Hg)CK (IU/mL)Static836±1017±1121439±5798Retrograde Perfusion840±1759±6*9123±716Data are mean±SEM; *-p
-
Myocardial Perfusion characteristics during Machine Perfusion for heart transplantation.
Surgery, 2008Co-Authors: Matthias Peltz, M.l. Cobert, L.m. West, David H. Rosenbaum, Michael E. JessenAbstract:Background Optimal parameters for Machine Perfusion preservation of hearts prior to transplantation have not been determined. We sought to define regional myocardial Perfusion characteristics of a Machine Perfusion device over a range of conditions in a large animal model. Methods Dog hearts were connected to a Perfusion device (LifeCradle™, Organ Transport Systems, Inc, Frisco, TX) and cold perfused at differing flow rates (1) at initial device startup and (2) over the storage interval. Myocardial Perfusion was determined by entrapment of colored microspheres. Myocardial oxygen consumption (MVO2) was estimated from inflow and outflow oxygen differences. Intra-myocardial lactate was determined by 1H magnetic resonance spectroscopy. Results MVO2 and tissue Perfusion increased up to flows of 15 mL/100 g/min, and the ratio of epicardial:endocardial Perfusion remained near 1:1. Perfusion at lower flow rates and when low rates were applied during startup resulted in decreased capillary flow and greater non-nutrient flow. Increased tissue Perfusion correlated with lower myocardial lactate accumulation but greater edema. Conclusions Myocardial Perfusion is influenced by flow rates during device startup and during the preservation interval. Relative declines in nutrient flow at low flow rates may reflect greater aortic insufficiency. These factors may need to be considered in clinical transplant protocols using Machine Perfusion.
