ACE inhibitors for the treatment of myocardial ischemia?

Abstract

Apart from their established use in the treatment of hypertension and heart failure, ACE inhibitors have been suggested to exert anti-ischemic effects. This article reviews the mechanisms of systemic and intracardiac angiotensin formation, as well as its interaction with the bradykinin, the prostaglandin, and the sympathetic nervous system. While high doses of angiotensin can precipitate myocardial ischemia. experimental data on a potential beneficial effect of ACE inhibitors on ischemic myocardial blood flow and function are inconsistent and controversial. Pooling the few available clinical data, several ACE inhibitors may attenuate myocardial ischemia at rest and during exercise. However, a significant fraction of patients does not benefit or even deteriorates. Recent experimental studies suggest a beneficial role of ACE inhibitors in attenuating reperfusion arrhythmias and postinfarction left ventricular remodeling. Unless the mechanisms and determinants of potential anti-ischemic actions of ACE inhibitors can be better defined, their use for treatment of myocardial ischemia cannot be recommended at present.

Cardioprotective Effects of Angiotensin II Type 1 Receptor Blockade with Olmesartan on Reperfusion Injury in a Rat Myocardial Ischemia‐Reperfusion Model

“…For example, Ertl et al [19] demonstrated that ACEI captopril reduced infarct size in anesthetized dogs. However, this cardioprotective effect of ACEIs may involve other mechanisms besides the RAAS system, such as their capacity to scavenge cytotoxic oxygen‐derived free radicals [20] or to prevent degradation of bradykinin [21,22]. Therefore, investigation of cardioprotective effects of RAAS by ACEIs is indirect and nonspecific [3].…”

Comparison of the effects of EXP3174, an angiotensin II antagonist and enalaprilat on myocardial infarct size in anaesthetized dogs

“…Indeed, it is not known whether the results obtained are the direct consequence of the blockade of angiotensin II production, or rather that of some of the indirect effects of ACEIs. For example, ACEIs might enhance the cardioprotective effects of endogenous bradykinin (Linder & Heusch, 1990;Martorana et al, 1990;Baumgarten et al, 1993). In addition, sulphydryl containing ACEIs such as captopril may exert cardioprotective effects during ischaemia and reperfusion through their capacity to scavenge oxygen-derived free-radicals (Westlin & Mullane, 1988;Przyklenk & Kloner, 1989;Grover et al, 1991).…”

ACE INHIBITION IN THE 1990s

“…Theoretically ACE inhibitors are beneficial in the treatment of patients with ischaemic heart disease, allowing redistribution of the blood flow to favour the coronary circulation and by decreasing sympathetic drive. 15 Furthermore, ACE inhibitors promote regression of left ventricular hypertrophy, 16 improve ventricular remodelling post-myocardial infarction, 17 scavenge free radicals and preserve renal function in the diabetic. 18 ACE inhibitors also cause less interference with serum lipids and glucose tolerance than most other cardiovascular agents. '…”

“…Reductions in blood pressure are not usually accompanied by tachycardia which is attributed to the vagomimetic effect of ACE inhibitors. Theoretically ACE inhibitors are beneficial in the treatment of patients with ischaemic heart disease, allowing redistribution of the blood flow to favour the coronary circulation and by decreasing sympathetic drive 15 . Furthermore, ACE inhibitors promote regression of left ventricular hypertrophy, 16 improve ventricular remodelling post‐myocardial infarction, 17 scavenge free radicals and preserve renal function in the diabetic 18 .…”