The effects of pretransplant cyclosporine therapy on rats grafted with twelve-hour cold-stored livers—with special reference to reperfusion injury

The effect of pretreatment with cyclosporine on liver preservation was studied using a rat liver transplant model. In a preliminary 1-week survival study, 59 liver transplants were performed. In group A, neither donors nor recipients were treated. In group B, the recipients were pretreated by a 3-day course of CsA (10 mg/kg/ day, p.o.), but the donors were untreated. In group C, the donor rats were pretreated for 3 days with the same doses of CsA as in group B, but the recipients were not treated. The donor livers in each group were stored for 12 hr at 4°C with Eurocollins solution and transplanted to the recipients. The CsA pretreatment to recipients (group B) significantly improved 1-week survival (57.1%, 8/14, P<0.01 versus control group A; 0%, 0/14 or group C; 14.3%, 2/14). To study lipid peroxidation and morphology, 72 rat livers were studied in 9 groups. In summary, CsA pretreatment to recipients resulted in suppression of the increase in MDA levels and amelioration of endothelial injury after transplantation. On the other hand, donor pretreatment exerted dual effects on the grafts; it ameliorated endothelial injury after reperfusion, but its hep- atotoxic action exacerbated hepatocellular damage during hypothermic storage. Our study suggests that CsA pretreatment, particularly to recipients, is beneficial in liver preservation for hepatic transplantation. The mechanisms are discussed with regard to ischemia/reperfusion injury to hepatic endothelium.