Circulatory and myocardial effects of different sodium antagonistic drugs in comparison to the calcium antagonist verapamil

The hemodynamic effects of intravenous class I and class IV antiarrhythmic drugs were investigated at different doses in comparison. In open-chest rats hemodynamic measurements in the intact circulation and isovolumic registrations 5 min after infusion of flecainide (2, 4, 8 mg/kg), disopyramide (1, 2, 4, 8 mg/kg), quinidine (5 and 10 mg/kg) and verapamil (0.35, 0.7, 1.5 mg/kg) were compared to saline controls. After clinically usual doses all investigated drugs had no effects on stroke volume, cardiac output, dp/dtmax and systemic resistance. The isovolumic pressure generating capacity of the left ventricle was not decreased at these doses. High intravenous doses of the drugs, however, caused a significant depression of myocardial performance (pressure generating capacity). Furthermore, flecainide decreased mean aortic pressure and heart rate, while disopyramide had no significant effect on the peripheral circulation. Blocking of the autonomic system (1 mg/kg propranolol and 0.1 mg/kg atropine) did not change significantly the action of disopyramide. Quinidine lowered heart rate and pressures. Verapamil reduced the heart rate and tended to decrease the mean aortic pressure. Besides the negative inotropic action of high doses the different hemodynamic profiles of class I and class IV antiarrhythmic drugs might be of importance for intravenous application in patients with left ventricular dysfunction.