Protective effect of the angiotensin-converting enzyme inhibitor captopril on postischemic myocardial damage in perfused rat heart.

This study was undertaken to examine whether a sulfhydryl-containing angiotensin-converting enzyme (ACE) inhibitor, captopril, improves postischemic cardiac function and myocardial metabolism in the perfused working rat heart, and to elucidate the mechanism by which captopril protects the myocardium from postischemic damage. Isolated rat hearts were perfused by the working heart technique for 15 min. Ischemia was then induced for 30 min by lowering the afterload pressure and coronary flow to zero. After ischemia, hearts were reperfused for 30 min by returning afterload pressure to 60 mmHg. Captopril, a non-sulfhydryl-containing ACE inhibitor, enalapril, or a type 1 angiotensin II receptor antagonist, DuP 753, was added to the perfusate 5 min before ischemia, and the treatment was continued during the first 10-min period of reperfusion. In all groups there was no significant difference in pressure-rate product, coronary flow, tissue levels of ATP, total adenine nucleotides (TANs), energy charge potential (ECP), or creatine phosphate (CrP) before and during ischemia. During reperfusion following ischemia, captopril significantly improved the recovery of pressure-rate product, coronary flow, and tissue levels of ATP, TAN, ECP, and CrP, but neither enalapril nor DuP 753 had an effect. In conclusion, captopril improved postischemic cardiac function and myocardial metabolism in the perfused rate heart and its effect was independent of the blunting of angiotensin II formation.