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.
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/kg (-)-verapamil (P less than 0.001) and 0.6 mg (+)-verapamil (P less than 0.01). 4. Intravenous administration of CaCl2 to dogs treated with either isomer of verapamil restored the contractile state and reversed atrioventricular blockade to sinus rhythm. Dog ventricles under the influence of concentrations of isomers of verapamil which, with normal plasmatic Ca2+-content, prevent fibrillation, consistently fibrillated after coronary artery occlusion when high doses of CaCl2 were administered. 5. The effects of the optical isomers of verapamil may occur predominantly via a blockade of the slow inward Ca2+-current.
D000818:Animals; D002118:Calcium / Q000097:blood; D002122:Calcium Chloride / Q000494:pharmacology; D002496:Central Venous Pressure / Q000187:drug effects; D003331:Coronary Vessels / Q000502:physiology; D003864:Depression, Chemical; D004285:Dogs; D004347:Drug Interactions; D005260:Female; D006321:Heart / Q000187:drug effects*; D006329:Heart Conduction System / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D008026:Ligation; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D012849:Sinoatrial Node / Q000187:drug effects; D013237:Stereoisomerism; D014693:Ventricular Fibrillation; D014700:Verapamil / Q000494:pharmacology*
D014700:Verapamil; D002122:Calcium Chloride; D002118:Calcium