Effects of new antiarrhythmic agent SS-68 on excitation conduction,electrical activity in Purkinje fibers and pulmonary veins: Assessment of safety and side effects risk

The compound ss-68 has been selected among numerous new derivatives of indole and demonstrated antiarrhythmic effects in animal models. the present study concerns several aspects of ss-68 safety and efficacy as a potential antiarrhythmic drug. the first estimation of atrioventricular conduction in mammalian heart under ss-68 has been carried out; effects of ss-68 in purkinje fibers and myocardium of pulmonary veins have been investigated. the drug weakly affects cardiac atrioventricular conduction: only high concentrations of ss-68 (≥10 μmol/l) significantly decrease this parameter. also,the drug weakly affects purkinje fibers automaticity,but effectively alters action potential waveform in purkinje fibers in a concentration-dependent manner. ss-68 (0.1–100 μmol/l) failed to induce any early or delayed afterdepolarizations in purkinje fibers both in basal conditions and under provocation of proarrhythmic activity by norepinephrine (ne). moreover,10 μmol/l ss-68 suppressed ne-induced extra-beats and rapid firing in purkinje fibers. in pulmonary veins only high concentrations of ss-68 significantly increased action potential duration,while lower concentrations (0.1–1 μmol/l) were ineffective. also,0.1–100 μmol/l ss-68 was unable to elicit arrhythmogenic alternations of action potential waveform in pulmonary veins. in conclusion,ss-68 has no proarrhythmic effects,such as afterdepolarizations or abnormal automaticity in used experimental models. © 2017 the authors