ELECTROPHYSIOLOGIC EFFECTS OF DETAJMIUM ON ISOLATED DOG CARDIAC VENTRICULAR AND PURKINJE-FIBERS

We studied the electrophysiologic effects of the antiarrhythmic compou nd detajmium (Tachmalcor) on isolated dog and rabbit cardiac preparati ons, applying the conventional intracellular microelectrode techniques . In dog ventricular muscle fibers (37 degrees C, stimulation frequenc y 1 Hz), 1 mu M detajmium did not change resting potential (RP), actio n potential amplitude (APA), AP duration measured at 90% of repolariza tion (APD(90)), or effective refractory period (ERP) significantly, bu t reduced maximum rate of depolarization (V-max) significantly from 23 6.7 +/- 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 mu M detajmium si gnificantly decreased APA from 111.1 +/- 12.3 to 100.0 +/- 2.5 mV (n = 8, p < 0.003), APD(90) from 359.0 +/- 17.5 to 262.1 +/- 12.3 ms (n = 8, p < 0.001) and V-max, from 687.5 +/- 57.2 to 523.7 +/- 58.2 V/s (n = 8, p < 0.001) without changing maximal diastolic potential or ERP/ A PD ratio significantly. The effect of detajmium on V-max in both dog v entricular muscle and Purkinje fibers was frequency dependent. Fractio nal V-max block was 0.185 +/- 0.008 1/AP. The recovery kinetics of V-m ax (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 mu M did not influe nce the beta-adrenoceptors or slow response APs in dog ventricular tis sue significantly. On the basis of its electrophysiologic effects, det ajmium, like prajmaline, encainide, or flecainide, can be best classif ied as a class I/C antiarrhythmic drug according to the Vaughan Willia ms' classification scheme.