Double-blind comparison of the acute effects of two relevant doses of oral nicorandil on central hemodynamics, left ventricular function, and myocardial contractility

Abstract

Nicorandil is a nicotinamide derivative with potent vasodilator properties. Oral and sublingual administration of this compound in patients with coronary artery disease resulted in a predominant reduction of afterload and a small decrease in left ventricular preload. The effects of nicorandil in different doses on contractile left ventricular (LV) function, however, are not well defined. The aim of the present study was to assess the effects of nicorandil on hemodynamics, left ventricular volume and function, as well as the LV contractility index dP/dt measured by Millar-tip manometers. A total of 16 patients with coronary artery disease were included in this study. After diagnostic coronary angiography and ventriculography, the patients randomly received either 10 or 20 mg of oral nicorandil. The hemodynamic parameters, cardiac output, and LV end-diastolic and systolic pressures were determined after 15, 30, and 60 minutes, and a second angiogram was performed 60 minutes after administration. The predominant effect was a decrease in the mean aortic pressure with a concomitant decrease in the peripheral arterial resistance. Clinically relevant changes in aortic pressure, systemic vascular resistance, and rate-pressure product, however, were documented only after oral administration of 20 mg nicorandil, as opposed to minimal changes in the 10 mg group. LV volume and cardiac output were not changed significantly. LV contractility remained unchanged during the observation period. The hemodynamic profile of this compound is dose-dependent afterload reduction without a change in contractility. Because there was no concomitant increase in heart rate, calculated oxygen consumption was reduced, especially in the higher dose group.