New preservation strategies for preventing liver grafts against cold ischemia reperfusion injury

Abstract

In spite of improvements in University of Wisconsin (UW) preservation solution, the injury from grafts during cold storage is an unresolved problem in liver transplantation. The aim of the present study was to evaluate the beneficial effect on ischemia-reperfusion injury associated with liver transplantation of the inversion of K(+) and Na(+) concentrations and the replacement of hydroxyethyl starch (HES) by polyethylene glycol (PEG) in UW preservation solution. Using an orthotopic liver transplantation model, the effects on rat liver preservation of a modified preservation solution (UW-PEG) were evaluated, based on the inversion of K(+) and Na(+) concentration and the replacement of HES by PEG 35 kDa (0.03 mmol/L) in UW preservation solution. The use of UW-PEG preservation solution ameliorated the biochemical and histological parameters of hepatic damage. Thus, at 24 h after transplantation, transaminase levels were reduced significantly when livers were preserved during 8 h in UW-PEG preservation solution compared with the original UW solution. In addition, histological findings revealed fewer and smaller areas of hepatocyte necrosis. The benefits of UW-PEG solution cannot be explained by modifications in oxidative stress or neutrophil accumulation associated with liver transplantation. However, the results of hepatic and portal blood flow indicated that the benefits of this modified preservation solution, UW-PEG were associated with improvements in the microcirculatory disorders after reperfusion. The UW-PEG solution, while retaining all the advantages of UW solution, improved hepatic ischemia-reperfusion injury associated with liver transplantation.