Effects of antiarrhythmic drugs on the monophasic action potential of the canine isolated, blood-perfused ventricular septum preparation

The present study was designed to combine the monophasic action potential (MAP) recording technique with a well-established canine isolated, blood-perfused ventricular septum preparation for examining, simultaneously, electrical and mechanical drug-induced changes. A MAP catheter was positioned onto the base of a papillary muscle for recording the local MAP, using a manual micromanipulator together with a commercially available catheter sheath to keep the optimal contact pressure against the Ventricular wall. The catheter sheath was filled with saline to eliminate the background electrical noise. Tetrodotoxin, disopyramide, lidocaine, and verapamil were used to clarify the potential utility of the preparation. Tetrodotoxin and lidocaine shortened the MAP duration, while disopyramide prolonged it. Verapamil slightly shortened the MAP duration but not significantly. Each drug showed negative inotropic and coronary vasodilator effects. Sodium channel blockers slowed intraventricular conduction and decreased the maximum upstroke velocity of MAP, while verapamil showed no effects. These results suggest that utilization of the blood-perfused ventricular septum preparation together with MAP recording will become a valuable model for evaluating drugs with multiple sites of action on cardiac muscles.