Electrophysiologic effects of detajmium on isolated dog cardiac ventricular and Purkinje fibers

Abstract

We studied the electrophysiologic effects of the antiarrhythmic compound detajmium (Tachmalcor) on isolated dog and rabbit cardiac preparations, applying the conventional intracellular microelectrode techniques. In dog ventricular muscle fibers (37 degrees C, stimulation frequency 1 Hz), 1 microM detajmium did not change resting potential (RP), action potential amplitude (APA), AP duration measured at 90% of repolarization (APD90), or effective refractory period (ERP) significantly, but reduced maximum rate of depolarization (Vmax) significantly from 236.7 +/- 28.9 to 177.3 +/- 22.5 V/s (n = 6, p < 0.01). In dog Purkinje fibers (37 degrees C, stimulation frequency 1 Hz), 1 microM detajmium significantly decreased APA from 111.1 +/- 12.3 to 100.0 +/- 2.5 mV (n = 8, p < 0.003), APD90 from 359.0 +/- 17.5 to 262.1 +/- 12.3 ms (n = 8, p < 0.001) and Vmax from 687.5 +/- 57.2 to 523.7 +/- 58.2 V/s (n = 8, p < 0.001) without changing maximal diastolic potential or ERP/APD ratio significantly. The effect of detajmium on Vmax in both dog ventricular muscle and Purkinje fibers was frequency dependent. Fractional Vmax block was 0.185 +/- 0.008 1/AP. The recovery kinetics of Vmax (offset kinetics) was extremely slow (time constant = 348.16 +/- 57.43 s) considerably slower than most of those of other antiarrhythmic drugs yet reported. Detajmium in concentration < 32 microM did not influence the beta-adrenoceptors or slow response APs in dog ventricular tissue significantly. On the basis of its electrophysiologic effects, detajmium, like prajmaline, encainide, or flecainide, can be best classified as a class I/C antiarrhythmic drug according to the Vaughan Williams' classification scheme.