CARDIAC EFFECTS OF VECURONIUM AND ITS INTERACTION WITH AUTONOMIC NERVOUS-SYSTEM IN ISOLATED PERFUSED CANINE HEARTS

The chronotropic and inotropic effects of vecuronium bromide and its interaction with the autonomic nervous system were investigated in the isolated, cross-circulated right atrial and left ventricular preparations of the dog. Vecuronium, injected into the external jugular vein of the support dog, induced dose-dependent decreases in heart rate and arterial blood pressure, and increased atrial contractile force with no change in sinus rate in isolated atrial preparations. Vecuronium (1-3,000-mu-g), injected into the sinus node artery of the isolated atrium, induced dose-dependent increases in atrial contractile force with small increases in sinus rate. Vecuronium also increased the ventricular contractile force in a dose-dependent manner. The positive inotropic effect was attenuated in part by propranolol, but not by either tetrodotoxin or imipramine. Vecuronium inhibited in a dose-related manner the negative chronotropic and inotropic responses to parasympathetic nerve stimulation and carbachol (CCh) and the negative followed by positive cardiac responses to nicotine, but did not attenuate the positive responses to sympathetic nerve stimulation. The ID50s for the responses to parasympathetic stimulation, CCh, and nicotine were not significantly different. Vecuronium enhanced the positive chronotropic and inotropic responses to sympathetic nerve stimulation, tyramine, norepinephrine, and isoproterenol. These results indicate that (a) vecuronium causes the positive inotropic responses mediated by nonadrenergic mechanisms and beta-adrenoceptors, (b) vecuronium blocks ganglionic and presynaptic nicotinic and postsynaptic muscarinic receptor-mediated responses similarly, and (c) vecuronium enhances beta-adrenoceptor-mediated responses in the dog heart.