PROTECTIVE EFFECT OF PROTEASE INHIBITOR, NAFAMOSTAT MESILATE(FUT-175), ON ISCHEMIA REPERFUSION INJURY IN CANINE LIVER.

Abstract

300 It is well known that complement activation, platelet agglutination and coagulation play a role in hepatic injury and microcirculatory disturbance after ischemic reperfusion. Serine protease inhibitor, Nafamostat mesilate(FUT-175), has been shown to suppress them in vitro studies. We investigated the protective effect of FUT-175 on ischemia and reperfusion injury of the liver. Adult female beagle dogs underwent 2hr hepatic vascular exclusion under venovenous bypass. FUT-175 was given to the animals by continuous intraportal infusion for 60min before ischemia and 4hr after reperfusion at a dose of 0.1 mg/kg/hr(FU group, n=5). No treated animals were used as the control (CT group, n=12). Animal survival, hepatic tissue blood flow(HTBF), liver function, NAG, complement activation (CH 50), platelet count and histopathology were analyzed. Two-week animal survival was 25% in CT group, 100% in FU group. Postreperfusion HTBF was markedly improved by the treatment. Treatment significantly attenuated liver enzyme release (ALT levels). Consumption of complement and platelet and platelet was suppressed. (Table)TableAdministration of serine protease inhibitor, FUT-175, ameliorated ischemia and reperfusion liver injury and protected microcirculatory disturbance by suppressing complement activity and platelet agglutination. We concluded that FUT-175 is promising agent for hepatic surgery and liver preservation.