Role of granulocyte elastase in ischemia/reperfusion injury of rat liver

Objective: To investigate the role of granulocyte elastase in ischemia/reperfusion injury of liver, the effect of ONO-5046, a granulocyte elastase inhibitor, was examined in ischemia/reperfusion-induced liver injury in rats. Design: Prospective, randomized, controlled study. Setting: Research laboratory at a university medical center. Subjects: Male Wistar rats, weighing 220 to 280 g. Interventions: Animals receiving continuous intravenous infusion of ONO-5046 (50 mg/kg/hr) were subjected to hepatic ischemia/reperfusion. Hepatic damage was evaluated by effects on bile formation capacity, plasma clearance of indocyanine green, and serum aminotransferase concentrations after ischemia/reperfusion. Measurements and Main Results: Hepatic dysfunction, observed after 60 mins of ischemia/reperfusion, led to a reduction in bile flow and to a decrease in the plasma clearance of indocyanine green. These indicators of hepatic dysfunction were prevented, to a large extent, by administration of ONO- 5046. Serum concentrations of aminotransferases increased after hepatic ischemia/reperfusion, peaking at 12 hrs of reperfusion. Increases in serum concentrations of aminotransferases were significantly inhibited by ONO- 5046. Conclusion: Granulocyte elastase derived from activated leukocytes may play a critical role in hepatic dysfunction and the subsequent hepatic injury induced by ischemia/reperfusion.