Background: In order to test the hypothesis that cardiac protein degradation contributes to the pathogenesis of myocardial stunning, the effect of protease inhibitor leupeptin on the postischemic hemodynamics and metabolic functioning was measured in isolated rat hearts.Material/Methods: Isolated rat hearts were perfused in Langendorff mode in the presence or absence of leupeptin (10 Kg/ml for 10 min.), and then subjected to 20 min. of normothermic ischemia and 30 min. of reperfusion. Aortic pressure, cardiac output, coronary flow (CF), global oxygen consumption (MVO2), carbon dioxide and [H+] release, and [Ca2+] uptake were investigated.Results: Hearts pretreated with leupeptin exhibited better postischemic return of systolic, diastolic and developed aortic pressure and faster return of CF to preischemic values during reperfusion. MVO2 and CO2 release were lower in this group in the 10th and 15th min. of reperfusion and [Ca2+] uptake higher in the 5th and 15th min. of reperfusionConclusions: Leupeptin protects the heart from myocardial stunning, which is consistent with the idea that proteases contribute to the pathogenesis of this phenomenon.