The effects of two vasodilators, papaverine and pentoxifylline (a methylxanthine derivative), on liver function after 19 hr hypothermic preservation were investigated. Hypothermic preservation was performed according to the standard technique, and liver hernodynamics and function were studied during 70 min immediately after reperfusion in an isolated perfused rat liver system. No significant changes occurred after hypothermic storage for 5 hr. However, when the storage was prolonged to 19 hr, bile flow and taurocholate intrinsic clearance were significantly reduced; transaminase release was markedly increased and histological studies demonstrated centrilobular necrosis. Concomitantly, liver blood flow was significantly reduced and intrahepatic vascular resistance was increased. Papaverine and pentoxifylline administered during preservation and at the time of reperfusion significantly improved all parameters. The improvement was more pronounced after pentoxifylline, and this group showed no significant difference in any of the studied parameters from the control livers. The results show that two vasodilators significantly protect the liver during long hypothermic preservation. The data suggest that abnormalities of liver microcirculation are of major importance in the pathogenesis of liver injury after hypothermic storage.
The liver is highly sensitive to ischemia; thus hypothermic preservation prior to transplantation cannot be extended for more than 10 hr (1). The prevention of liver damage after prolonged hypothermic preservation would be a major advance in liver transplantation. However, the mechanisms of ischemic liver injury are poorly understood. It has been generally assumed that the primary target in injury is the hepatocyte (2). It has been proposed that cell death could occur as a result of the generation in situ of oxygen-derived free radicals (3) and/or a massive cellular influx of calcium (4), as suggested by the effectiveness of free radical scavengers (51, allopurinol