Systemic and coronary hemodynamic actions of the novel inotropic agent, ibopamine, and the de-esterified metabolite and active form, epinine: relationship to left ventricular performance in the dog

GA Kopia, EH Ohlstein and RR Ruffolo

Department of Pharmacology, Smith Kline & French Laboratories, Swedeland, Pennsylvania.

The relationship between the systemic hemodynamic, inotropic and coronary blood flow actions of the novel inotropic pro-drug, ibopamine, which is the 3,4-diisobutyryl ester derivative of the active form, epinine, was examined in pentobarbital-anesthetized, vagotomized dogs prepared for the recording of systemic arterial blood pressure, heart rate, left ventricular developed pressure and end-diastolic pressure, left ventricular dP/dt, aortic blood flow, left circumflex coronary artery blood flow and lead II ECG. All animals were given i.v. infusions of vehicle followed by 10 min infusions of either epinine (1.1, 3.3, 10 and 30 micrograms/kg/min, n = 4) or ibopamine (3.3, 10, 30 and 100 micrograms/kg/min, n = 4). Both epinine and ibopamine produced dose-dependent increases in mean arterial blood pressure, heart rate, left ventricular developed pressure, left ventricular dP/dt, aortic blood flow, coronary blood flow, left ventricular minute work, stroke work, total peripheral vascular resistance and rate- pressure product. Both epinine and ibopamine decreased coronary vascular resistance, although only the decrease produced by ibopamine achieved statistical significance (P less than .05). Examination of the dose-response curves for epinine and ibopamine showed epinine to be 3- to 4-fold more potent than ibopamine with respect to increasing coronary blood flow, left ventricular stroke work, left ventricular dP/dt and rate-pressure product. However, neither drug increased myocardial work, myocardial oxygen consumption or contractility to a greater extent than the increase in coronary blood flow.(ABSTRACT TRUNCATED AT 250 WORDS)

Volume 246, Issue 2, pp. 434-440, 08/01/1988
Copyright © 1988 by American Society for Pharmacology and Experimental Therapeutics