ELECTROPHYSIOLOGICAL EFFECTS OF DRIDOCAINIDE ON ISOLATED CANINE, GUINEA-PIG AND HUMAN CARDIAC TISSUES

The cellular electrophysiological effects of dridocainide (EGIS-3966), a novel class I antiarrhythmic agent, was studied using conventional microelectrode techniques in canine cardiac Purkinje fibres and papill ary muscle preparations obtained from humans and guinea-pigs. In each preparation, dridocainide (0.6-2 mu mol/l) decreased the maximum veloc ity of action potential upstroke (V-max) in a frequency-dependent mann er, although marked differences were observed in its effects in Purkin je fibre and ventricular muscle preparations. In canine Purkinje fibre s, action potential duration measured at 50% and 90% of repolarization was decreased, while action potential duration measured at 10% of rep olarization was increased by dridocainide. In addition, the plateau of the action potential was depressed by the drug. These changes in acti on potential configuration were not observed in guinea pig or human pa pillary muscles. The offset kinetics of the dridocainide-induced V-max block were different in Purkinje fibres and in ventricular muscle: th e slow time constant of recovery of V-max was estimated to be 2.5 s in dog Purkinje fibre and 5-6 s in human and guinea-pig papillary muscle . In guinea-pig papillary muscle, the rate of onset of the V-max block was 0.15 and 0.2 per action potential in the presence of 0.6 and 2 mu mol/l dridocainide, respectively. Dridocainide also decreased the for ce of contraction in this preparation. On the basis of the present res ults, dridocainide appears to posess mixed class I.C and I.A propertie s, with I.C predominance in human and guinea-pig ventricular muscle. P resent results also indicate that results of conventional classificati on of class I drugs may depend on the parameters chosen, as well as on the preparation selected.