GRAFT FUNCTION AND SURVIVAL DEPEND PRIMARILY ON HOST FACTORS IN COMPROMISED RECIPIENT MODELS OF ORTHOTOPIC LIVER TRANSPLANTATION IN THE RAT

Background. Experimental models of liver transplantation use normal recipients, although most patients undergoing liver transplantation suffer from acute or chronic liver failure. This study was designed to analyze the outcome of orthotopic liver transplantation in compromised rat hosts. Methods. Recipient animals were either rats with D-galactosamine-induced acute or rats with chronic liver failure secondary to common bile duct ligation. Liver damage was evaluated by monitoring enzymes, bilirubin, ammonia levels, prothrombin, thrombin time, and cytokines. In vivo function of hepatocytes and sinusoidal endothelial cells were evaluated by indocyanine green and hyaluronic acid uptake. Transplantation was performed in normal, acute, and chronic liver failure rats at different time points using either freshly harvested or cold-preserved syngeneic livers. Results. Survival with fresh grafts decreased significantly when transplants were performed 48 hr after the induction of acute liver failure. No rats with acute liver failure survived transplantation with grafts stored for 12 or 24 hr although in chronic failure survival was more 80%. Survival of acute liver failure rats receiving 6 hr preserved grafts was 16.6% compared with 83.3% observed with fresh grafts transplanted at the same time point after D-galactosamine injection. Elevated tumor necrosis factor-a and interleukin-1b levels as well as impaired sinusoidal endothelial cell function were detected in acute liver failure rats with 6 h preserved grafts. Conclusion. These results suggest that preoperative status and different host factors have a significant effect on outcome and graft function after liver transplantation in rats. Ischemia/reperfusion injury is inevitable in organ transplantation, and it is considered to be the major determinant of early postoperative graft function. It has been demonstrated that sinusoidal endothelial cells (SEC) in the liver are the most susceptible to damage due to cold preservation (1). Allograft dysfunction after orthotopic liver transplantation (OLT) is relatively common (2, 3). Although experimental data show that liver graft function is inversely proportional to the time of cold preservation and the extent of ischemia/ reperfusion injury (4), allograft dysfunction in patients does not appear to be exclusively related to preservation time, suggesting that other, host-derived factors may contribute to graft dysfunction. Although many presurgical parameters have been evaluated in patients to reveal the effects of the recipient’s condition on graft function and outcome after OLT, no universally recognized criteria and indices have yet been established (5, 6). In large part, the difficulty in determining these parameters can be attributed to the wide range of confounding variables involved in the heterogenous pool of human transplant recipients and donors. The nature and severity of the underlying disease, immune response, graft quality as well as technical factors play a very significant role in postoperative graft function and, ultimately, outcome. By using inbred rats in a syngeneic OLT model, many of these confounding variables can be limited or eliminated. The aim of this study was to establish a compromised recipient model for OLT and evaluate the influence of these hosts on graft function and survival. Two compromised recipient models were established and evaluated; acute and chronic liver failure. Acute liver failure (ALF) was induced using D-galactosamine (DG) and chronic liver failure (CLF) was induced by common bile duct ligation.