With increasing time of cold preservation, levels of highenergy nucleotides in the liver are reducing. The authors hypothesized that cold preservation sensitizes hepatocyte function to ischemic injury occurring during graft rewarming and that the injury can be prevented by short-term reperfusion. Rat livers were cold-preserved in University of Wisconsin solution for 0 to 18 hours and ischemically rewarmed for 0 to 45 minutes to simulate the implantation stage of transplantation. Hepatobiliary function was assessed using a blood-free perfusion model. In comparison with controls, neither 18-hour preservation nor 45-minute ischemic rewarming significantly influenced hepatocyte function. Compared with livers subjected to 45-minute ischemic rewarming, livers subjected to 9-hour preservation and 45-minute rewarming, and livers subjected to 18-hour preservation and 45-minute rewarming exhibited, respectively: 3.8 and 24 times reduced bile production, 4.3-and 116-fold decreased taurocholate excretion, and 3.1 and 42 times depressed bromosulfophthalein excretion. Thirty-minute oxygenated warm reperfusion after 9-and 18-hour preservation nearly completely blunted sensitization of hepatocyte function to rewarming ischemia. The authors found that shortterm oxygenated reperfusion restored adenine nucleotides in liver tissue to the values found before organ preservation and that reperfusion with energy substrate containing solutions increased tissue adenosine triphosphate concentration to a higher level than that found before preservation. In conclusion, sensitization of hepatocyte function to rewarming ischemia increases disproportionally with storage time, suggesting that this phenomenon may play a role in graft dysfunctions with increasing liver preservation time. Shortterm oxygenated reperfusion of the liver may protect hepatocyte functions against warm ischemic insult, even after extended preservation. (HEPATOLOGY 2000;32:289-296.) Preservation injury is a major cause of morbidity and mortality in liver transplant recipients. 1 Because hypothermic preservation causes selective liver injuries to nonparenchymal cells, while hepatocytes appear well-preserved, it is currently hypothesized that sinusoidal endothelial-cell impairment, 2-5 microcirculatory disturbances, 6,7 activation of Kupffer cells, [8][9][10] and sinusoidal accumulation of leukocytes 11,12 are major causes of preservation-related graft failure. This hypothesis is strongly supported by a number of studies showing that sinusoidal endothelial cells lose their function with increasing time of cold storage 13-15 and die during a brief period of reperfusion. 16,17 On the other hand, most parameters of hepatocyte function of livers reperfused after 18-or 24-hour cold preservation were found to be comparable with control livers perfused immediately after hepatectomy. [18][19][20] In clinical transplantation, however, several authors identified that during the implantation stage of transplantation, prolonged warm ischemic time (WIT), preferentially influencing hepat...

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Determination of ACP, alanine transaminase, and aspartate transaminase activities in the washout solution can be used as a rapid, simple, and cost-effective way for screening liver preservation solutions. The results also suggest that KC were not involved in preservation-induced liver damage.