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.
Kuban' State Medical University, Sedina, 4, Krasnodar, Russia.
Saida K
SK
Bogus
Lomonosov Moscow State University, Leninskie Gory, 1, Moscow, Russia; Pirogov Russian National Research Medical University, Ostrovityanova, 1, Moscow, Russia.
Vladislav S
VS
Kuzmin
Lomonosov Moscow State University, Leninskie Gory, 1, Moscow, Russia; Pirogov Russian National Research Medical University, Ostrovityanova, 1, Moscow, Russia. Electronic address: abram340@mail.ru.
Denis V
DV
Abramochkin
Chemical Department of Southern Federal University, Zorge, 7, Rostov-on-Don, Russia.
Konstantin F
KF
Suzdalev
Kuban' State Medical University, Sedina, 4, Krasnodar, Russia.
Pavel A
PA
Galenko-Yaroshevsky
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D006329:Heart Conduction System / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D011667:Pulmonary Veins / Q000187:drug effects* / Q000502:physiology; D011690:Purkinje Fibers / Q000187:drug effects* / Q000502:physiology; D011817:Rabbits; D017208:Rats, Wistar
D000889:Anti-Arrhythmia Agents; D007211:Indoles
Action potential; Antiarrhythmic drug; Arrhythmia; Conduction; Pulmonary veins