The marked myocardial depressant effect of verapamil

An experiment was designed to measure accurately the primary effect of verapamil on myocardial contractility by infusion of the drug directly into the coronary artery of open-chested anesthetized dogs. A marked myocardial depressant effect, which was dose and time dependent, was noted during verapamil infusion at the infused area only. The percent decrease in contractile force ranged from 8.8 at an infusion rate (mg/min) of 0.55 X 10(-2) to 36.8 at 5.5 X 10(-2). Similar changes were observed in the first derivative of the contractile force. No changes were observed in the left ventricular systolic or end-diastolic pressure and only a mild increase in contractile force was noted in the control (noninfused) area. The depressant effect of verapamil was sustained. Recovery time after 5 min of verapamil infusion was dose dependent, ranging from 10 to 45 min. During the recovery period, an overshoot of the contractile force was observed in dogs on the higher doses only. We concluded that verapamil in clinically relevant doses has a marked negative inotropic effect of long duration and therefore should be used with caution in patients with depressed left ventricular function. Cessation of the verapamil treatment may cause a transient increase in myocardial contractility, which might be hazardous in patients with angina pectoris who have compromised coronary blood flow.