Impact of Temperature on Porcine Liver Machine Perfusion From Donors After Cardiac Death.

Normothermic machine perfusion (NMP) has been introduced as a promising technology to preserve and possibly repair marginal liver grafts. The aim of this study was to compare the effect of temperature on the preservation of donation after cardiac death (DCD) liver grafts in an ex vivo perfusion model after NMP (38.5°C) and subnormothermic machine perfusion (SNMP, 21°C) with a control group preserved by cold storage (CS, 4°C). Fifteen porcine livers with 60 min of warm ischemia were preserved for 10 h by NMP, SNMP or CS (n = 5/group). After the preservation phase all livers were reperfused for 24 h in an isolated perfusion system with whole blood at 38.5°C to simulate transplantation. At the end of transplant simulation, the NMP group showed significantly lower hepatocellular enzyme level (AST: 277 ± 69 U/L; ALT: 22 ± 2 U/L; P < 0.03) compared to both SNMP (AST: 3243 ± 1048 U/L; ALT: 127 ± 70 U/L) and CS (AST: 3150 ± 1546 U/L; ALT: 185 ± 97 U/L). There was no significant difference between SNMP and CS. Bile production was significantly higher in the NMP group (219 ± 43 mL; P < 0.01) compared to both SNMP (49 ± 84 mL) and CS (12 ± 16 mL) with no significant difference between the latter two groups. Histologically, the NMP livers showed preserved cellular architecture compared to the SNMP and CS groups. NMP was able to recover DCD livers showing superior hepatocellular integrity, biliary function, and microcirculation compared to SNMP and CS. SNMP showed some significant benefit over CS, yet has not shown any advantage over NMP.

[1]  J. Fung,et al.  Ex Vivo Normothermic Machine Perfusion Is Safe, Simple, and Reliable , 2015, Surgical innovation.

[2]  S. Keshavjee,et al.  Subnormothermic ex vivo liver perfusion reduces endothelial cell and bile duct injury after donation after cardiac death pig liver transplantation , 2014, Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society.

[3]  W. Baldwin,et al.  Sanguineous normothermic machine perfusion improves hemodynamics and biliary epithelial regeneration in donation after cardiac death porcine livers , 2014, Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society.

[4]  M. Yarmush,et al.  Subnormothermic Machine Perfusion for Ex Vivo Preservation and Recovery of the Human Liver for Transplantation , 2014, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[5]  Charles M. Miller,et al.  Role of Vasodilation during Normothermic Machine Perfusion of DCD Porcine Livers , 2014, The International journal of artificial organs.

[6]  W. Baldwin,et al.  Absence of Fc&ggr;RIII Results in Increased Proinflammatory Response in Fc&ggr;RIII-KO Cardiac Recipients , 2013, Transplantation.

[7]  Michael E. Sutton,et al.  Ex vivo Normothermic Machine Perfusion and Viability Testing of Discarded Human Donor Livers , 2012, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[8]  M. Yarmush,et al.  Subnormothermic machine perfusion at both 20°C and 30°C recovers ischemic rat livers for successful transplantation. , 2012, The Journal of surgical research.

[9]  G. Otto,et al.  Histological examination and evaluation of donor bile ducts received during orthotopic liver transplantation—a morphological clue to ischemic-type biliary lesion? , 2012, Virchows Archiv.

[10]  M. Yarmush,et al.  A simplified subnormothermic machine perfusion system restores ischemically damaged liver grafts in a rat model of orthotopic liver transplantation , 2012, Transplantation research.

[11]  M. Yarmush,et al.  Excorporeal normothermic machine perfusion resuscitates pig DCD livers with extended warm ischemia. , 2012, The Journal of surgical research.

[12]  R. Porte,et al.  Regeneration of human extrahepatic biliary epithelium: the peribiliary glands as progenitor cell compartment , 2012, Liver international : official journal of the International Association for the Study of the Liver.

[13]  J. Gugenheim,et al.  Ischemia-Reperfusion Injury and Ischemic-Type Biliary Lesions following Liver Transplantation , 2012, Journal of transplantation.

[14]  L. Joutsi-Korhonen,et al.  New Insights into von Willebrand Disease and Platelet Function , 2012, Seminars in Thrombosis & Hemostasis.

[15]  Charles M. Miller,et al.  Hepatic blood flow plays an important role in ischemia‐reperfusion injury , 2011, Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society.

[16]  C. Fondevila,et al.  Superior Preservation of DCD Livers With Continuous Normothermic Perfusion , 2011, Annals of surgery.

[17]  P. Friend,et al.  Hepatic Steatosis and Normothermic Perfusion—Preliminary Experiments in a Porcine Model , 2011, Transplantation.

[18]  J. Pirenne Time to think out of the (ice) box. , 2010, Current opinion in organ transplantation.

[19]  P. Friend,et al.  Ex-vivo normothermic liver perfusion: an update , 2010, Current opinion in organ transplantation.

[20]  P. Friend,et al.  Normothermic Perfusion: A New Paradigm for Organ Preservation , 2009, Annals of surgery.

[21]  R. Freeman,et al.  Report of the Paris consensus meeting on expanded criteria donors in liver transplantation , 2008, Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society.

[22]  D. Geller,et al.  Factors in the pathophysiology of the liver ischemia-reperfusion injury. , 2008, The Journal of surgical research.

[23]  R. Mangus,et al.  Comparison of histidine‐tryptophan‐ketoglutarate solution and University of Wisconsin solution in extended criteria liver donors , 2008, Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society.

[24]  S. S. St. Peter,et al.  Extended preservation of non‐heart‐beating donor livers with normothermic machine perfusion , 2002, The British journal of surgery.

[25]  G. Alexander,et al.  Successful extracorporeal porcine liver perfusion for 72 hr1 , 2002, Transplantation.

[26]  P. Friend,et al.  Advantages of normothermic perfusion over cold storage in liver preservation , 2002, Transplantation.

[27]  P. Friend,et al.  Liver and kidney preservation by perfusion , 2002, The Lancet.

[28]  P. Friend,et al.  Normothermic perfusion of the isolated liver. , 2001, Transplantation proceedings.

[29]  L. Wsólová,et al.  Bile analysis as a tool for assessing integrity of biliary epithelial cells after cold ischemia--reperfusion of rat livers. , 2000, Cryobiology.

[30]  J. Lemasters,et al.  Reperfusion injury to donor livers stored for transplantation. , 1995, Liver transplantation and surgery : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society.

[31]  A. Demetris,et al.  Intrahepatic biliary strictures after liver transplantation. , 1994, Radiology.

[32]  K. Nakamura,et al.  Isolated perfusion of rat livers: effect of temperature on O2 consumption, enzyme release, energy store, and morphology. , 1993, Nihon geka hokan. Archiv fur japanische Chirurgie.

[33]  B. Horwitz Temperature Effects on Oxygen Uptake of Liver and Kidney Tissues of a Hibernating and a Non-Hibernating Mammal , 1964, Physiological Zoology.