Neurohumoral activation during acute myocardial ischaemia. Effects of ACE inhibition

Abstract

ACE inhibition may be useful in several manifestations of ischaemic heart disease, such as heart failure due to ischaemic cardiomyopathy. Recent evidence suggests that these effects may also be present in normotensive patients with ischaemic heart disease without heart failure. Theoretically, converting-enzyme inhibition, through coronary and systemic vasodilating effects and negative inotropic properties, should have a favourable effect on the myocardial oxygen supply/demand ratio and, hence, affect the incidence and severity of myocardial ischaemia. It is doubtful, however, whether these cardiac and extracardiac properties of ACE inhibitors really underlie its potential antiischaemic effects, at least in the average patient with ischaemic heart disease without concomitant heart failure and hypertension. Recent animal and human studies indicate that converting-enzyme inhibitors may modulate myocardial ischaemia by reducing ischaemia-induced circulating neurohumoral activation. It has been shown that, depending on the severity of ischaemia, the circulating renin-angiotensin system may become activated together with an increase in circulating catecholamine levels. ACE inhibition suppresses this neuroendocrine stimulation during ischaemia and modulates subsequent systemic and, presumably, also coronary vasoconstriction. In addition to these effects on circulating neurohormones, ACE inhibition could affect myocardial ischaemia through a number of local actions, e.g. modulation of tissue (cardiac) angiotensin II formation and bradykinin breakdown, stimulation of prostaglandin synthesis and, in the use of sulphydryl compounds, by affecting EDRF formation. Whether ACE inhibitors have clear antiischaemic effects in all clinical conditions is uncertain. Their efficacy to limit exercise-induced ischaemia has been questioned. In contrast, pacing-induced ischaemia in patients at rest is clearly prevented by ACE inhibition. This differential effect may be related to a more pronounced difference in circulating neurohormones during exercise per se. It also suggests that ACE inhibitors may be particularly useful as (additional) antiischaemic therapy in patients with angina at rest, e.g. unstable angina and the acute phase of myocardial infarction.