Cold-preservation-induced sensitivity of rat hepatocyte function to rewarming injury and its prevention by short-term reperfusion

Abstract

With increasing time of cold preservation, levels of high-energy 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 short-term 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. Short-term oxygenated reperfusion of the liver may protect hepatocyte functions against warm ischemic insult, even after extended preservation.