Effects of beta-adrenergic blocking drug pindolol (LB46) on cardiac fibers in relation to its membrane effects.

Direct membrane effects and beta-adrenergic blocking action of pindolol were studied comparatively on isolated perfused cardiac fibers of dogs. In Purkinje fibers, the duration of transmembrane action potential decreased in concentrations higher than 0.5 mg/L. Maximum rate of depolarization also decreased in higher concentrations (5.0 mg/L or more). The functional refractory period decreased to a lesser degree compared with the decrease of the action potential duration. Nevertheless, slow-rising action potentials could not be abolished in premature responses, probably because of membrane depressant effects of this drug. In ventricular muscle fibers, these changes were minimum in the same range of concentrations. On the other hand, 0.05 mg/L of pindolol which was close to the therapeutic plasma concentrations and had no effect on action potentials of both Purkinje and ventricular muscle fibers, minimized the increase in automaticity of Purkinje fibers induced by 0.2 mg/L of isoproterenol. It is rationally speculated that the mechanism of antiarrhthmic action of pindolol is mainly due to its beta-adrenergic blocking action.