O. Hala et al., ELECTROPHYSIOLOGIC EFFECTS OF DETAJMIUM ON ISOLATED DOG CARDIAC VENTRICULAR AND PURKINJE-FIBERS, Journal of cardiovascular pharmacology, 24(4), 1994, pp. 559-565
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.