Potentiation of Adverse Effects of Cold by Warm Ischemia in Circulatory Death Donors for Porcine Liver Transplantation

Abstract

BackgroundWider use of donors after circulatory death (DCD) could reduce mortality on the liver transplantation waiting list. We previously reported that pig livers exposed to ≥30 minutes of warm ischemia followed by 4 hours of cold ischemia are at high risk of primary graft nonfunction. We sought to determine how prolonged cold ischemia, after a short, normally well-tolerated period of warm ischemia affects graft function and recipient survival using a porcine model of liver transplantation. Materials and MethodsLivers were transplanted after exposure to no warm plus 4 hours cold ischemia (group 1); 15 minutes of warm and 4 hours of cold ischemia (group 2); no warm and 8 hours of cold ischemia (group 3); or 15 minutes of warm and 8 hours of cold ischemia (group 4). Recipient survival, graft dysfunction incidence, liver function (prothrombin time), hepatocellular damage (aspartate aminotransferase), sinusoidal cell function (hyaluronic acid), and inflammation (tumor necrosis factor-α) were recorded after transplantation. Biopsies were scored for ischemia–reperfusion injury. ResultsDay 4 survival in group 4 was 0% versus 100%, 83%, and 100% in groups 1, 2, and 3, respectively. Recipients in group 4 exposed to short warm but prolonged cold ischemia displayed severe graft dysfunction, the highest peak transaminase, the greatest inflammatory response, more sinusoidal endothelial cell dysfunction and, the worst histologic score for ischemia–reperfusion injury. ConclusionsLiver grafts from DCD donors, even when exposed to short periods of warm ischemia, did not tolerate prolonged cold ischemia well and should be transplanted without delay.