Mechanism of the antifibrillatory action of Chinoin-103, a new antiarrhythmic drug.

The studies deal with the relationship between antifibrillatory and electrophysiological effects of Chinoin-103 (CH-103) on right ventricular myocardium of cats. In experiments carried out on right ventricles of open-chested cats, CH-103 markedly increased the fibrillation threshold in a dose-dependent manner. In electrophysiological experiments performed on isolated, electrically driven right ventricular papillary muscles of cats, the drug, at the concentrations needed to increase the fibrillation threshold, decreased the maximum rate of rise of action potential (Vmax) without changing the resting membrane potential. The reduction of Vmax was found to be voltage- and use-dependent. Steady state inactivation of Vmax, an index of the fast inward Na current, was shifted to more negative potentials by CH-103. During a train of stimuli applied after a long resting period, the amplitude of Vmax decreased gradually and reached a new steady state within 8-10 action potentials, thus suggesting that CH-103 inhibited the rate of recovery from inactivation of the fast inward Na+ current. It is concluded that the antifibrillatory effect of CH-103 may be due to a use-dependent block of fast inward Na+ current, which can suppress extrasystoles and tachycardias.