ELECTROPHYSIOLOGIC EFFECTS OF DIPHENIDOL IN ISOLATED CARDIAC TISSUE

¹ Department of Cardiology, Cedars-Sinai Medical Center, Department of Medicine, University of California, Los Angeles, California

Diphenidol, a potent antiemetic, has previously been shown to possess significant antiarrhythmic effects in the intact animal. In the present investigation the effects of diphenidol (1 x 10^-7 to 1 x 10^-4 M) were studied in canine Purkinje fiber and rabbit right atrial preparations. In Purkinje fiber, low concentrations (1 x 10^-7 M) of diphenidol resulted in significant depression of dv/dt, shortening of action potential duration and shift of the membrane responsiveness curve down and to the right. Diphenidol, 1 x 10^-5 M, resulted in depression of total action potential amplitude (-11%), overshoot (-33%), dv/dt (-29%), action potential duration at 95% repolarization (-21%), effective refractory period (-4%), and conduction velocity (-17%), as well as membrance responsiveness. Toxic concentrations of diphenidol (1 x 10^-4 M) resulted in further depression of these variables. At all concentrations tested, the Purkinje fiber effective refractory period to action potential duration ratio was greater than 1. After induction of arrhythmias secondary to exposure to toxic concentrations of ouabain (2 x 10^-7 M), the addition of diphenidol (1 x 10^-6 M) to the ouabain perfusate promptly (15 minutes) reversed the rhythm disturbrance. Enhanced automaticity induced in Purkinje fiber by epinephrine perfusion was also reversed following the addition of diphenidol (1 x 1^-6 M). Superfusion of isolated rabbit right atrial preparations with increasing diphenidol concentrations resulted in progressive slowing of the sinus rate. However, exposure to 1 x 10^-4 M diphenidol resulted in marked sinus slowing with resultant escape beating. The present data support previous in vivo studies suggesting that diphenidol has marked antiarrhythmic effects, especially for rhythm disturbances secondly to digitalis overdosage.