Drug s 1997; 54 Suppl. 5: 31-4 1 001 2-6667/97/0005{)()31/ S05.fJJ /O © Ads International Limited. All rightsreserved. Cardioprotection by ACE Inhibitors in Myocardial Ischaemia/Reperfusion The Importance of Bradykinin Gerd Heusch, [ochen Rose and Thomas Ehring Department of Pathophysiology, Centre of Internal Medicine, University of Essen Medical School, Essen, Germany Summary Myocardial ischaemia, when severe and sustained for more than 40 minutes, results in irreversible damage , i.e. myocardial infarction. However, with early reperfusion , damage is reversible . Complete recovery of contractile function re- quires some time, despite fully or almost fully restored blood flow. This phenom- enon has been termed myocardial stunning . There is experimental evidence showing that angiotensin converting enzyme (ACE) inhibitors limit the develop- ment of infarct size, reduce the incidence of ischaemic and reperfusion arrhyth- mias, and enhance the recovery of contractile function of stunned myocardium. These cardioprotective effects of ACE inhibitors are mediated by an attenuated degradation of bradykinin . There is overwhelming evidence that angioten- sin converting enzyme (ACE) inhibitors exert ben- eficial effects in patients with arterial hypertension or chronic heart failure, and after myocardial in- farction .U '<' This review focuses on the experimen- tal evidence for a protective role of ACE inhibitors in instances of an abrupt reduction in myocardial perfusion leading to irreversible cellular damage, i.e. myocardial necrosis, to life-threatening ven- tricular arrhythmias and, after reperfusion, to re- versibly depressed contractile function, i.e. stunned myocardium. 1. ACE Inhibitors and Infarct Size During acute myocardial infarction, the renin- angiotensin system and the sympathetic nervous system are activated either by a direct reflex action originating in the ischaemic myocardiumlf or secondary to a decrease in arterial pressure.P'U Even in the absence of haemodynamic effects of myocardial infarction, commonly used pharmaco- logical interventions such as vasodilator therapy and diuretic administration can activate these sys- tems. The renin-angiotensin system acts to pre- serve arterial pressure by retention of sodium and water via the stimulation of aldosterone secretion, while both the renin-angiotensin and the sympa- thetic nervous systems act to preserve arterial pres- sure through vasoconstriction in the circulation of the intestine, skeletal muscle and skin, and thereby maintain blood flow to the cerebral, coronary, and renal circulation. However, both sympathetic acti- vation[8]and the potent vasoconstrictor angiotensin W 9 ] may also limit blood flow to the ischaemic myocardium . Blockade of the renin-angiotensin system may therefore exert beneficial effects on the ischaemic myocardium and, finally, attenuate the development of myocardial necrosis.