Metabolic and inotropic effects of verapamil in perfused rat heart

The effect of verapamil on myocardial contractility, heart adenosine 3', 5'-monophosphate (cyclic AMP) and cardiac phosphorylase a activity was studied in isolated perfused rat hearts. In a concentration of 0.025 mug/ml, verapamil decreased force of contraction 50% and caused a significant fall in heart cyclic AMP within 4 to 5 min after perfusion with the drug was begun. When perfusion of the heart with medium containing verapamil was continued for 60 min, contractile force gradually returned to control. at the end of 60 min of perfusion with verapamil, the myocardial concentration of cyclic AMP was not different from that measured in hearts perfused with contro medium for a similar time period. Isoproterenol, given at the point of maximal contractile depression induced by verapamil, restored normal force of contraction and raised cardiac cyclic AMP to the same level as that observed when the catecholamine was given to untreated hearts; When methoxamine was administered to hearts depressed by verapamil, contractility returned to normal, but cyclic AMP content remained below control values.