Functional Human Liver Preservation and Recovery by Means of Subnormothermic Machine Perfusion

Abstract

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.

Peritransplant Energy Changes and Their Correlation to Outcome After Human Liver Transplantation

“…The system was primed with the diluted whole-blood and set to warm at 37 °C. Simultaneously, the liver was prepared for perfusion by cannulation of the portal vein, arterial system and bile duct as described previously 17,20 . The liver was then flushed with ice-cold Lactated Ringer’s solution supplemented with 100 mL/L albumin 25%.…”

Comparison of Aerobic Preservation by Venous Systemic Oxygen Persufflation or Oxygenated Machine Perfusion of Warm-Ischemia-Damaged Porcine Kidneys

“…In order to increase the use of less optimal organs for transplantation, aerobic extracorporeal normothermic, subnormothermic, and hypothermic preservation techniques have been developed which demonstrate an improved preservation quality compared to anaerobic preservation for kidney, liver, heart, lung, and pancreas grafts [8,9,10,11,12,13]. The benefit from aerobic preservation has been related to the fact that even at hypothermia, a residual metabolism is operative which has restorative capacities if oxygen is provided [8,14].…”

Liver ex situ machine perfusion preservation: A review of the methodology and results of large animal studies and clinical trials

“…These unexpected results compared to the UK trial was speculated to be related to the higher proportion of DCD livers (44% Edmonton trial versus 20% for UK or Toronto trials) or the prolonged cold ischemia time (median, 2 hours 47 minutes) due to uncommonly complex back‐table reconstructions, and HTK donor flush in the Edmonton trial. Additionally, the superiority of COR and SNMP in porcine livers sparked the first successful application or COR in clinical liver transplantation . Rewarming therapies, the newest methodology in machine preservation, may become the ultimate compromise with their ability to capture advantages of relative convenience as compared with NMP, longevity of storage comparable to HMP or SCS, optimal resuscitation in predictive animal models, and predictive ex vivo assessment prior to transplantation.…”

“…Additionally, the superiority of COR and SNMP in porcine livers sparked the first successful application or COR in clinical liver transplantation. (41,79) Rewarming therapies, the newest methodology in machine preservation, may become the ultimate compromise with their ability to capture advantages of relative convenience as compared with NMP, longevity of storage comparable to HMP or SCS, optimal resuscitation in predictive animal models, and predictive ex vivo assessment prior to transplantation.…”