Effects of bepridil on the electrophysiologic properties of isolated canine and rabbit myocardial fibers.

Bepridil hydrochloride is a relatively new calcium antagonist which appears to have a complex pharmacologic profile, but its concentration-response characteristics with respect to its electrophysiologic properties of varying concentrations (0.1 to 10.0 micrograms/ml) of the drug were therefore determined in rabbit and canine myocardial fiber preparations in vitro by standard microelectrode techniques. The following were measured: sinus cycle length (SCL), action potential amplitude (APA), maximum diastolic potential (MDP), threshold potential (TP), slope of phase 4 depolarization, action potential duration (APD), and dV/dtmax of phase O depolarization (Vmax) in rabbit sinoatrial (SA) node. Also measured were APA, membrane resting potential (MRP), Vmax, APD at 50% and 90% repolarization (APD50 and APD90), and effective refractory period (ERP) in rabbit atria and canine Purkinje fibers and ventricular muscle. At the lowest concentrations bepridil selectively prolonged SCL by reducing the slope of phase 4 and decreased APA and MDP in a concentration-dependent manner in the sinus node. At higher concentrations, bepridil exerted additional effects in producing concentration-dependent decreases in APA and Vmax in rabbit atria and in canine Purkinje fibers and ventricular muscle. During superfusion with 1.0 micrograms/ml bepridil, Vmax fell by 22.2% (p less than 0.05) in Purkinje fibers and by 11.8% (NS) in ventricular muscle; at 10.0 micrograms/ml, Vmax fell by 46.5% (p less than 0.01), respectively. The depression of Vmax was frequency dependent. There was a differential effect of bepridil on repolarization in Purkinje fibers as compared to that in ventricular muscle.(ABSTRACT TRUNCATED AT 250 WORDS)