Optical isomers of verapamil on canine heart. Prevention of ventricular fibrillation induced by coronary artery occlusion, impaired atrioventricular conductance and negative inotropic and chronotropic effects
Abstract
Effects of optical isomers of verapamil on the canine heart were measured with a pressure catheter in the left ventricle and with the electrocardiogram. 1. Both isomers of verapamil caused impaired atrioventricular conduction. slowed the rate of the sinus pacemaker and depressed the contractile state of the myocardium. (-)-Verapamil was consistently more potent than (+)-verapamil in producing these effects. (-)/(+) potency ratios of 10 and 3 were estimated for atrioventricular blockade and for the negative chronotropic effect, respectively. 2. Negative inotropic effects of 0.06-2.0 mg/kg of (+)-verapamil were determined on hearts paced at constant rate. A similar dose-response relationship could not be established with (-)-verapamil because at concentration higher than 0.06 mg/kg the hearts did not follow the supraventricular driving stimulus. With doses of (-)- and (+)-verapamil which produced the same slowing of the sinus pacemaker rate in spontaneously beating hearts, (-)-verapamil caused greater negative inotropic effects than (+)-verapamil. 3. The following doses of isomers of verapamil reduced the incidence of ventricular fibrillation induced by coronary artery ligation: 0.2 mg/kg (-)-verapamil (P less than 0.001), 0.6 mg...Continue Reading
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