Enalaprilat, a new parenteral angiotensin-converting enzyme inhibitor: rapid changes in systemic and coronary hemodynamics and humoral profile in chronic heart failure

Systemic and coronary hemodynamic, metabolic and humoral effects of a new intravenous angiotensin-converting enzyme inhibitor, enalaprilat, were evaluated in 14 patients with chronic heart failure. Onset of hemodynamic action occurred within 15 minutes and persisted for 6 hours. At the time of peak effect, there was a significant reduction in mean arterial pressure (-21%) and pulmonary capillary wedge pressure (-33%). Systemic vascular resistance decreased by 32% and stroke volume index increased by 20%. These systemic hemodynamic changes indicate improved left ventricular function. There was a substantial sustained reduction in rate-pressure product initially without a change in coronary sinus blood flow or myocardial oxygen consumption. There was also reduced myocardial oxygen extraction and augmented coronary sinus oxygen saturation at 30 minutes and 1 hour. In three patients, abnormal myocardial lactate extraction, present before enalaprilat, changed to uptake after enalaprilat, indicating amelioration of myocardial ischemia that was not clinically manifest. Systemic catecholamine levels and myocardial catecholamine balance did not change. Plasma renin activity increased and plasma aldosterone decreased. These findings suggest that enalaprilat produces inhibition of the angiotensin-converting enzyme and consequent beneficial systemic hemodynamic changes in heart failure. In some patients with heart failure, silent myocardial ischemia at rest can occur and can be alleviated with enalaprilat. Decreased myocardial oxygen extraction, increased coronary sinus oxygen saturation and lack of expected decrease in coronary sinus blood flow despite reduced rate-pressure product suggest transient coronary vasodilation by enalaprilat.

This article has been cited by other articles:

				G. K. Lund, M. F. Wendland, A. Shimakawa, H. Arheden, F. Ståhlberg, C. B. Higgins, and M. Saeed Coronary Sinus Flow Measurement by Means of Velocity-encoded Cine MR Imaging: Validation by Using Flow Probes in Dogs Radiology, November 1, 2000; 217(2): 487 - 493. [Abstract] [Full Text]

				J. A. Taylor, D. L. Carr, C. W. Myers, and D. L. Eckberg Mechanisms Underlying Very-Low-Frequency RR-Interval Oscillations in Humans Circulation, August 11, 1998; 98(6): 547 - 555. [Abstract] [Full Text] [PDF]

				D. Annane, E. Bellissant, E. Pussard, R. Asmar, F. Lacombe, E. Lanata, O. Madonna, M. Safar, J.-F. Giudicelli, and P. Gajdos Placebo-Controlled, Randomized, Double-Blind Study of Intravenous Enalaprilat Efficacy and Safety in Acute Cardiogenic Pulmonary Edema Circulation, September 15, 1996; 94(6): 1316 - 1324. [Abstract] [Full Text]

				K. Sudhir, T. M. Chou, S. J. Hutchison, and K. Chatterjee Coronary Vasodilation Induced by Angiotensin-Converting Enzyme Inhibition In Vivo : Differential Contribution of Nitric Oxide and Bradykinin in Conductance and Resistance Arteries Circulation, May 1, 1996; 93(9): 1734 - 1739. [Abstract] [Full Text]