Protection of the Myocardium Against Postischemic Reperfusion Damage

Abstract

Restoration of coronary blood flow in the ischemic myocardium is necessary to prevent irreversible cellular damage, although it may result in hazardous consequences. Because thrombolysis during myocardial infarction is designed to salvage a maximal number of myocardial cells threatened by ischemia, a concomitant intervention that reduces cellular damage caused by reperfusion will improve the net result of such a procedure. The adjunctive use of angiotensin-converting enzyme (ACE) inhibitors with thrombolytic therapy early during acute myocardial infarction offers theoretic advantages. In the acute phase, captopril may scavenge free radicals, blunt the catecholamine response, elicit coronary vasodilation, and increase prostacyclin and bradykinin levels. In the chronic phase, remodeling may be attenuated. This article summarizes study results that indicate that ACE inhibitors play an important role in cardioprotection in the acute phase of myocardial ischemia followed by reperfusion. The sulfhydryl group-containing ACE inhibitors probably have an additional protective effect through an interaction with bradykinin or through scavenging of free radicals. At present, a large number of controlled clinical trials mainly focusing on the effects of ACE inhibition in the chronic phase are under way. However, only a few studies concentrate on the effect of acute intervention with ACE inhibitors in ischemia-reperfusion, i.e., thrombolysis in myocardial infarction. In April 1990, under the auspices of the Interuniversity Cardiology Institute of The Netherlands, a large nationwide acute intervention trial with captopril in 280 patients receiving thrombolytic therapy was started, the Captopril and Thrombolysis Study. The primary hypothesis of this study supposes a very early effect of converting enzyme inhibition on evolving myocardial damage due to ischemia and the consequences of early reperfusion.