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 el astase inhibitor, was examined in ischemia/reperfusion induced liver i njury in rats, Design: Prospective, randomized, controlled study, Sett ing: Research laboratory at a university medical center, Subjects: Mal e Wistar rats, weighing 220 to 280 g, Interventions: Animals receiving continuous intravenous infusion of OMO-5046 (50 mg/kg/hr) were subjec ted to hepatic ischemia/reperfusion. Hepatic damage was evaluated by e ffects on bile formation capacity, plasma clearance of indocyanine gre en, and serum aminotransferase concentrations after ischemia/reperfusi on. 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 indi cators of hepatic dysfunction were prevented, to a large extent, by ad ministration of ONO-5046, Serum concentrations of aminotransferases in creased after hepatic ischemia/reperfusion, peaking at 12 hrs of reper fusion. Increases in serum concentrations of aminotransferases were si gnificantly inhibited by ONO-5046, Conclusion: Granulocyte elastase de rived from activated leukocytes may play a critical role in hepatic dy sfunction and the subsequent hepatic injury induced by ischemia/reperf usion.