Summary
There are multiple mechanisms whereby ACE inhibitors could be beneficial during myocardial ischemia and reperfusion, including: i) reduced formation of angiotensin II ii) decreased metabolism of bradykinin, iii) antioxidant activity, and iv) possibly other unknown mechanisms. Reduced formation of angiotensin II should be beneficial because this peptide exerts several actions that are potentially detrimental to the ischemic/reperfused myocardium, including vasoconstriction, increased release of norepinephrine, stimulation of phospholipase C and/or A2, and increased afterload with an attendant increase in oxygen demands. Reduced metabolism of bradykinin could be beneficial by increasing myocardial glucose uptake, by causing vasodilation, and by stimulating production of endothelium-derived relaxing factor and prostacyclin. Although earlier studies suggested that sulfhydryl-containing ACE inhibitors scavenge superoxide anions, recent data have shown that these drugs scavenge hydroxyl radical and hypochlorous acid with no effect on superoxide anion. Studies in isolated hearts have demonstrated that ACE inhibitors attenuate the metabolic, arrhythmic, and contractile dearangements associated with ischemia and reperfusion, and have suggested that such beneficial effects are mediated by potentiation of bradykinin and/or increased synthesis of prostacyclin. Studies in models of myocardial stunning after brief (15-min) ischemia in vivo (anesthetized dogs) suggest that ACE inhibitors enhance the recovery of contractile function after a single brief ischemic episode. No data are available regarding the effect of these drugs on myocardial stunning after a prolonged, partly reversible episode, after multiple consecutive brief ischemic episodes, and after global ischemia. The mechanism for the salutary effects of ACE inhibitors on stunning remains a mystery. It may involve an antioxidant action (in the case of thiol-containing molecules) or potentiation of prostaglandins (in the case of non-thiol-containing molecules). What is clear is that the enhanced recovery of function effected 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 effects of ACE inhibitors on myocardial infarct size remain controversial.
Further studies will be necessary to conclusively establish whether ACE inhibitors can protect against the detrimental effects of myocardial ischemia and reperfusion. Nevertheless, the evidence provided thus far is encouraging and warrants an in-depth assessment of the role of these drugs in attenuating myocardial ischemia/reperfusion injury.
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© 1993 Dr. Dietrich Steinkopff Verlag GmbH & Co. KG, Darmstadt
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Zughaib, M.E., Sun, JZ., Bolli, R. (1993). Effect of angiotensin-converting enzyme inhibitors on myocardial ischemia/reperfusion injury: an overview. In: Grobecker, H., Heusch, G., Strauer, B.E. (eds) Angiotensin and the Heart. Steinkopff. https://doi.org/10.1007/978-3-642-72497-8_11
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