[ACE inhibition: mechanisms of cardioprotection in chronic experimental heart failure]

Abstract

In 1984 we demonstrated in an animal model of chronic congestive heart failure due to rapid right ventricular pacing in chronically instrumented dogs, that the inhibition of the renin-angiotensin-aldosterone system by captopril from the onset of pacing has beneficial effects on hemodynamic and neurohumoral mechanisms. In contrast to control animals, dogs on a chronic therapy with the ACE-inhibitor showed no significant increase in peripheral vascular resistance, a reduced decline of cardiac output and no significant increase of mean pulmonary arterial pressure. Chronic ACE-inhibition led to a significant reduction of the secretion of aldosterone, to an attenuation of the activation of the sympathetic activity and to a prevention of inappropriate stimulation of vasopressin secretion. This was associated with a reduction in symptoms and a lack of fluid retention, whereas control animals developed pleural infusions and ascites. Similar beneficial effects have been demonstrated in rats following myocardial infarction during a long-term therapy with captopril on hemodynamic parameters, heart size, and survival. Thus, early inhibition of the renin-angiotensin-aldosterone system in heart failure may be an attractive approach for treatment in patients with ventricular dysfunction even before symptoms develop.