Cardioprotective effects of the serine protease inhibitor aprotinin after regional ischemia and reperfusion on the beating heart

Abstract

Objective: Early coronary reperfusion of the ischemic myocardium is a desired therapeutic goal to preserve myocardium. However, reperfusion itself contributes to an additional myocardial injury (ie, reperfusion injury), which has been attributed to neutrophil infiltration with subsequent release of proteases and oxygen-derived radicals. We studied the effects of the serine protease inhibitor aprotinin (Trasylol) on myocardial ischemia and reperfusion in a rat model. Methods: The effects of aprotinin (5000 and 20,000 U/kg) were examined in vivo in a rat model of regional myocardial ischemia (20 minutes) and long-term reperfusion (24 hours). Cardioprotecive effects were determined by means of measurement of creatine kinase and myeloperoxidase activity within the myocardium, as well as histochemical analysis. Results: Aprotinin (20,000 U/kg) administrated 2 minutes before reperfusion significantly attenuated myocardial injury expressed as creatine kinase washout compared with that seen in vehicle-treated rats (65 ± 25 vs 585 ± 98 creatine kinase difference in units per 100 mg, P