Acute effects of amiodarone in the isolated dog heart.

Abstract

Direct injection of amiodarone (10-1000 micrograms) into the sinus node artery of the isolated blood-perfused dog atrium produced dose-dependent negative inotropic and chronotropic responses that were unaffected by atropine. Intraarterial amiodarone also had a negative inotropic action on isolated left ventricular muscle preparations electrically paced at 1.5 to 2.0 Hz. A continuous infusion of 100 micrograms/min of amiodarone significantly suppressed the positive chronotropic effect of norepinephrine whether expressed in percent change or in absolute values; its positive inotropic effect expressed in percent change was not suppressed but rather enhanced by amiodarone. Calcium chloride induced positive chronotropic and inotropic effects expressed in percent change were, respectively, slightly suppressed and enhanced by amiodarone. Intravenous injection of amiodarone (5 mg/kg) decreased the heart rate and blood pressure of the support dog and produced a negative inotropic response in the isolated left ventricular muscle preparation perfused with arterial blood from the support dog. These results suggest first, that amiodarone has direct negative inotropic and chronotropic effects that are not mediated by cholinergic mechanisms and second, that it has a depressive action on norepinephrine and calcium-induced positive chronotropic effects and an enhancing action on their positive inotropic effects.