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

With increasing time of cold preservation, levels of high-energy nucleotide s in the liver are reducing. The authors hypothesized that cold preservatio n sensitizes hepatocyte function to ischemic injury occurring during graft rewarming and that the injury can be prevented by short-term reperfusion, R at 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 impl antation stage of transplantation, Hepatobiliary function was assessed usin g a blood-free perfusion model. in comparison with controls, neither 18-hou r preservation nor 45-minute ischemic rewarming significantly influenced he patocyte function. Compared with livers subjected to 45-minute ischemic rew arming, livers subjected to 9-hour preservation and 45-minute rewarming, an d livers subjected to 18-hour preservation and 45-minute rewarming exhibite d, respectively: 3.8 and 24 times reduced bile production, 4.3- and 116-fol d decreased taurocholate excretion, and 3.1 and 42 times depressed bromosul fophthalein excretion. Thirty-minute oxygenated warm reperfusion after 9- a nd 18-hour preservation nearly completely blunted sensitization of hepatocy te function to rewarming ischemia, The authors found that short-term oxygen ated 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, sens itization of hepatocyte function to rewarming ischemia increases disproport ionally with storage time, suggesting that this phenomenon may play a role in graft dysfunctions with increasing liver preservation time. Short-term o xygenated reperfusion of the liver may protect hepatocyte functions against warm ischemic insult, even after extended preservation.