EFFECT OF ANGIOTENSIN-CONVERTING ENZYME-INHIBITORS ON MYOCARDIAL-ISCHEMIA REPERFUSION INJURY - AN OVERVIEW

There are multiple mechanisms whereby ACE inhibitors could be benefici al during myocardial ischemia and reperfusion, including: i) reduced f ormation of angiotensin II, ii) decreased metabolism of bradykinin, ii i) antioxidant activity, and iv) possibly other unknown mechanisms. Re duced formation of angiotensin II should be beneficial because this pe ptide exerts several actions that are potentially detrimental to the i schemic/reperfused myocardium, including vasoconstriction, increased r elease of norepinephrine, stimulation of phospholipase C and/or A2, an d increased afterload with an attendant increase in oxygen demands. Re duced metabolism of bradykinin could be beneficial by increasing myoca rdial glucose uptake, by causing vasodilation, and by stimulating prod uction of endothelium-derived relaxing factor and prostacyclin. Althou gh earlier studies suggested that sulfhydryl-containing ACE inhibitors scavenge superoxide anions, recent data have shown that these drugs s cavenge hydroxyl radical and hypochlorous acid with no effect on super oxide anion. Studies in isolated hearts have demonstrated that ACE inh ibitors attenuate the metabolic, arrhythmic, and contractile dearangem ents associated with ischemia and reperfusion, and have suggested that such beneficial effects are mediated by potentiation of bradykinin an d/or increased synthesis of prostacyclin. Studies in models of myocard ial stunning after brief (15-min) ischemia in vivo (anesthetized dogs) suggest that ACE inhibitors enhance the recovery of contractile funct ion after a single brief ischemic episode. No data are available regar ding the effect of these drugs on myocardial stunning after a prolonge d, partly reversible episode, after multiple consecutive brief ischemi c episodes, and after global ischemia. The mechanism for the salutary effects of ACE inhibitors on stunning remains a mystery. It may involv e an antioxidant action (in the case of thiol-containing molecules) or potentiation of prostaglandins (in the case of non-thiol-containing m olecules). What is clear is that the enhanced recovery of function eff ected by these drugs is not due to hemodynamic effects, inhibition of the converting enzyme per se, or an ''antiischemic'' action (since the drugs were effective when given at the time of reperfusion). The effe cts of ACE inhibitors on myocardial infarct size remain controversial. Further studies will be necessary to conclusively establish whether A CE inhibitors can protect against the detrimental effects of myocardia l ischemia and reperfusion. Nevertheless, the evidence provided thus f ar is encouraging and warrants an in-depth assessment of the role of t hese drugs in attenuating myocardial ischemia/reperfusion injury.