Evaluation of University of Wisconsin cold-storage solution in warm hypoxic perfusion of rat liver: the addition of fructose reduces injury.

Abstract

University of Wisconsin cold-storage solution (UW solution) has markedly improved organ preservation for liver transplantation. However, the efficacy of this solution in preserving hepatocyte viability during warm ischemia is undefined; hence, the effects of UW solution on warm hypoxic injury in the isolated perfused rat liver were examined. Livers were perfused using a modified protocol that included a period of hypoxic perfusion with isosmotic Krebs' solution at the end of each experiment. Hepatic injury was evaluated by aspartate aminotransferase (AST) release into the perfusate and the trypan blue perfusion technique. Although UW solution appeared to decrease hepatic injury during hypoxic perfusion, as reflected by low AST release, perfusion with UW solution led to hepatocyte shrinkage and cessation of bile flow even under oxygenated conditions. UW solution did not protect against warm hypoxic injury, as assessed by AST release into the perfusate (182 +/- 15 U/mL, mean +/- SD) or trypan blue staining of the dead hepatocyte nuclei (56% +/- 5%). However, the addition of fructose to UW solution resulted in a significant decrease in AST release (66 +/- 15 U/mL) and parenchymal cell death (39% +/- 7%). These data suggest that the addition of fructose or other gluconeogenic substrates may complement the overall hepatoprotective effects of UW solution, particularly during periods of warm hypoxia.