Elsevier

American Heart Journal

Volume 111, Issue 2, February 1986, Pages 271-279
American Heart Journal

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

https://doi.org/10.1016/0002-8703(86)90139-0Get rights and content

Abstract

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 μg/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 dVdtmax of phase 0 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 μg/ml bepridil, Vmax fell by 22.2% (p < 0.05) in Purkinje fibers and by 11.8% (NS) in ventricular muscle; at 10.0 μg/ml, Vmax fell by 46.5% (p < 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. The APD50 and APD90 in Purkinje fibers were shortened, respectively, by 29.6% (p < 0.05) and 5.5% (NS) at 1.0 μg/ml, and by 45.0% (p < 0.01) and 14.1% (p < 0.05) at 10.0 μg/ml. By contrast, in ventricular muscle, they were lengthened by 17.1% (NS) and 16.7% (p < 0.05) at 1.0 μg/ml, and by 37.9% (p < 0.05) and 33.7% (p < 0.01) at 10.0 μg/ml. Slow-response potentials induced by high K+ (20 mM) and isoproterenol (2 × 10−6M) were suppressed by bepridil (0.1 μg/ml) but reversed by high Ca2+ concentrations (7.2mM). Automatic firing induced by isoproterenol (1 × 10−6M) in Purkinje fibers was slowed by bepridil (0.01 μg/ml) by both the depression of phase 4 depolarization and the elevation of the threshold potential. The data indicate that bepridil has a relative selectivity of inhibitory action for the slow channel with a significant depressant effect on the fast sodium inward current at higher concentrations. Bepridil differs from most fast-channel inhibitors in exerting a differential effect on repolarization in Purkinje fibers vs ventricular muscle.

References (24)

  • R Dibianco et al.

    Bepridil for chronic stable angina pectoris: Results of a prospective multicenter, placebo-controlled, dose-ranging study in 77 patients

    Am J Cardiol

    (1984)
  • JA Hill et al.

    Effect of bepridil in patients with chronic stable angina: Results of a multicenter trial

    Circulation

    (1984)
  • Cited by (0)

    Supported in part by grants from the Medical Research Service of the Veterans Administration and the American Heart Association Greater Los Angeles Affiliate.

    View full text