Effects of bepridil on transmembrane action potentials recorded from isolated canine cardiac tissues. Studies on normal and infarct-zone Purkinje fibres and ventricular muscle cells.

Abstract

The electrophysiological effects of bepridil (1.9 mumol/l), a drug with antianginal and antiarrhythmic actions, were studied on transmembrane action potentials recorded from isolated cardiac tissues using standard microelectrode techniques. Recordings were made (a) from normal canine cardiac Purkinje fibres in major false tendons, (b) from partially depolarized subendocardial Purkinje fibres in 24 h infarct zones, and (c) from ventricular muscle preparations. It was found that at cycle lengths between 1000 and 300 ms, bepridil exerted use-dependent effects on the maximum rate of depolarization of phase zero (dV/dtmax) and action potential amplitude (APA) in both normal and infarct zone Purkinje fibres (IZPF), but that the effects in the IZPF were relatively greater. Bepridil did not affect maximum diastolic potential (MDP) in normal Purkinje fibres, but decreased it in IZPF. Bepridil lengthened total action potential duration under all conditions, but exerted variable effects on the duration of the plateau (APD-60 mV). In normal ventricular muscle cells (basic cycle length = 1000 ms), bepridil only decreased dV/dtmax. In regard to effects on automatic activity in canine Purkinje fibres, bepridil resembled slow inward current blocking drugs: it did not decrease the rate of normal automaticity or the slope of phase 4 depolarization in normal fibres (with MDPs greater than -80 mV), but it did slow or abolish abnormal automaticity in IZPF (with MDPs less than -60 mV). Bepridil also abolished triggering in 24 h IZPF.