Concentration-dependent protection by captopril against ischemia-reperfusion injury in the isolated rat heart.

The purpose of this study was to investigate the protective effects of captopril at three concentrations (1, 10 and 80 micrograms/ml) against reperfusion injury after 15 min of coronary ligation in the isolated perfused rat heart. During ischemia, the apex displacement (AD) and pressure rate index (PI) decreased markedly and only in the presence of 80 micrograms captopril less reduction of the PI was obtained (p less than 0.05). Upon reperfusion, the AD and PI improved significantly in all captopril treated hearts, depending on the concentration used, whereas the untreated hearts showed a further deterioration (p less than 0.05). Ventricular fibrillation upon reperfusion occurred in 6/6 untreated hearts, but only in 4/6 hearts at 1 microgram/ml, in 2/6 hearts at 10 micrograms/ml and 0/6 hearts at 80 micrograms/ml captopril with a significantly shorter duration (p less than 0.05). In control hearts a marked overflow of purines and norepinephrine was found in the coronary effluent upon reperfusion. In contrast, captopril decreased purine overflow, most at 80 micrograms/ml, and norepinephrine levels were undetectable at all concentrations. These results indicate concentration-dependent protective effects of captopril after local ischemia and reperfusion, already present at therapeutic levels. Reduction of cellular injury and suppression of NE release appear to play an important role in the improvement of mechanical function and the reduction of reperfusion arrhythmias.