Cardiovascular action of verapamil in the dog with particular reference to myocardial contractility and atrioventricular conduction

Abstract
Verapamil (Isoptin®) caused a dose-dependent peripheral vasodilation, increase in myocardial contractility, and tachycardia in the anaesthetized dog. Propranolol pre-treatment blocked the cardiac stimulation following verapamil but the vasodilation was unaltered. Inflation of a thoracic aortic balloon prevented the fall in intravascular pressure and reduced the tachycardia and positive inotropic responses. These experiments suggest that clinical doses of verapamil cause peripheral vasodilation which leads to a sympathetic reflex induced increase in heart rate and myocardial contractility. Verapamil also had a direct myocardial depressant action which became evident at doses above the range used clinically. The drug increased the PR interval in conscious dogs for up to 60 minutes. This effect was partly mediated through cholinergic stimulation and partly through a direct depression on atrioventricular conduction.