Direct myocardial and coronary effects of enalaprilat in patients with dilated cardiomyopathy: Assessment by a bilateral intracoronary infusion technique

Abstract

Angiotensin II elicits contractile responses in the coronary arteries and myocardial tissue, which suggests that blockade of the renin-angiotensin system by specific agents should lead to both coronary vasodilation and an alteration of left ventricular inotropism. The present work was designed to delineate - independently from its systemic effects - the intrinsic actions of an angiotensin converting-enzyme inhibitor on the coronary circulation and left ventricular function. To minimize peripheral effects, a bilateral intracoronary infusion of enalaprilat (0.05 mg·min-1, 1 ml·min-1 in each coronary artery) was performed in 16 patients with dilated cardiomyopathy. All patients had normal coronary arteriograms. In 12 patients (group I) the intracoronary infusion of enalaprilat resulted in minimal peripheral changes, with a 5% reduction in the mean aortic pressure (p < .05) and no significant alteration in indexes of preload, i.e., left ventricular end-diastolic pressure and volume, or of afterload, i.e., left ventricular end-systolic stress and systemic resistances. Myocardial oxygen consumption was also unaffected by the intracoronary infusion of enalaprilat. Coronary vasodilation was demonstrated by a significant elevation of coronary sinus blood flow (+19%, from 181 ± 73 to 214 ± 79 ml·min-1, p < .001) and a reduction of coronary resistance (-18%, from 0.51 ± 0.17 to 0.41 ± 0.15 mm Hg·ml-1·min, p < .001), with a parallel increase in coronary sinus oxygen content and pressure (both p < .05). Oxygen extraction by the myocardium was reduced (p < .01). The intracoronary infusion of enalaprilat resulted, on the other hand, in a significant deterioration of all indexes of left ventricular function: cardiac index (-9%, from 2.59 ± 0.61 to 2.36 ± 0.64 liters·min-1·m-2, p < .01), ejection fraction (-12%, from 0.32 ± 0.11 to 0.28 ± 0.10, p < .01). In 4 patients (group II) with similar baseline characteristics, intracoronary enalaprilat induced the same hemodynamic alterations, with return to basal values after cessation of the intracoronary infusion and no significant alteration of plasma renin activity and plasma aldosterone. This study demonstrates that, when its peripheral effects are avoided by a bilateral intracoronary infusion technique, enalaprilat produces both a selective vasodilation of the coronary arteries and a negative inotropic effect on left ventricular contractility in patients with dilated cardiomyopathy.