Cardiovascular effects of dobutamine, dopamine and isoproterenol on the whole animal and isolated cross-perfused atrium in dogs.

Abstract

Abstract-The right atrium of the dog was isolated and cross-perfused with arterial blood of another (donor) dog anesthetized with pentobarbital. When dobutamine, dopamine or isoproterenol was administered intravenously to the donor dog, the following changes were elicited in them: Dobutamine caused slight biphasic changes in heart rate. Dopamine induced biphasic changes in blood pressure and heart rate. Isoproterenol produced a decrease in blood pressure and a marked increase in heart rate. All these 3 catecholamines, however, induced positive chronotropic and inotropic effects in a similar fashion on the isolated atrium cross-perfused with blood of the donor dog. When injected into the cannulated sinus node artery of the isolated dog atrium, dobutamine, dopamine or isoproterenol induced monophasic positive chronotropic and inotropic effects in a dose-related manner, although the potency of each of the drugs was different. Dobutamine-induced effects were abolished by propranolol, but not modified by imi pramine which suppressed significantly tyramine-and dopamine-induced effects. The difference in dobutamine-induced chronotropic effect between the whole animal and the isolated atrium may be due mainly to modification by extracardiac factors in the whole animal.Dobutamine is a synthetic catecholamine developed by Tuttle and Mills (1) to provide a clinically more useful inotropic agent having less side effects. Indeed, dobutamine directly increases myocardial contractility without inducing marked tachycardia or greatly changing peripheral arterial resistance in intact dogs (1-3). In the cat papillary muscle, dobutamine increases the con tractility more but the automaticity less than did isoproterenol (1). However, no report is available concerning the effect of dobutamine assessed in isolated dog heart preparations. Thus, in the present study, we attempted to compare chronotropic and inotropic effects of dobutamine, dopamine and isoproterenol using the isolated dog atrial preparation which was perfused with the arterial blood of the donor dog (4, 5). We administered these three catecholamines intravenously to the donor dog or intraarterially to the isolated atrium to observe their direct cardiac chrono tropic and inotropic effects and probable modification of these effects by extracardiac factors. Materials and MethodsTwenty mongrel dogs weighing 11-25 kg were anesthetized with sodium pentobarbital (30 mg/kg, i.v.). The right atrium was quickly removed and immersed in Tyrode solution at 4-10°C. The right atrium was then perfused with blood from the carotid artery of a heparinized donor dog. Perfusion pressure was kept constant at 100 mm Hg. The atrium which was usually subjected to a resting tension of 2 g was suspended in the bath filled with blood maintained at a constant temperature of 37'C. Atrial rate and isometric tension development of the isolated atrium and systemic blood pressure and heart rate of the donor dog were simultaneously measured during the experiments. The details of the preparation are descri...

Pharmacological analysis of positive chronotropic and inotropic responses to etilefrine in isolated dog heart preparations

“…These results suggest that etilefrine is a highly selective 13-1 adrenergic agonist like dobutamine. From our laboratory, Chiba et al [31] and Akahane et al [15] reported that the potency of dobutamine, i.e., sinus rate ED (40%) and atrial tension ED (100%) were 4.1-5.6nmol and 1.6-1.8nmol, respectively, in the atrial preparations, and ventricular tension ED (100%) was 5.1nmol in the ventricular preparations. Therefore, etilefrine is 5 times less potent than dobutamine in chronotropism and 7-16 times less potent than dobutamine in inotropism.…”