[Comparative study of electrophysiological mechanisms of anti-arrhythmia III class agents, cardiocyclide, nibentan, and sotalol during experimental myocardial infarction and sympathetic stimulation].
Electrophysiological mechanisms of the action of cardiocyclide, nibentan, and sotalol--antiarrhythmic agents of class III--was studied in dogs with experimental myocardial infarction induced by a two-step occlusion of the coronary artery. Cardiocyclide exhibited the properties typical of the class III antiarrhythmics by prolonging the ventricular repolarization and increasing the effective refractory periods in the atrium and ventricles. The degree of manifestation of these antiarrhythmic effects of cardiocyclide is independent of the induced heart rate, which is related to the ability of this drug to block the slow activation component (IKs) of the delayed rectified potassium current. Nibentan elongates the QT interval and increases the effective atrial and ventricular refractory periods, but the effect was dependent of the stimulation frequency. Sotalol, which also exhibited the properties of a class III antiarrhythmogen possessing beta-blocking activity, produced more pronounced inhibiting action upon the sinus node function and conduction (in comparison with the analogous effects of cardiocyclide). This is probably related to the ability of sotalol to block the cardiac adrenoreceptors. The effect of sotalol is also frequency-dependent, which is related to the blocking of rapid activating component (IKr) of) of the delayed rectified potassium current. On the background of isoproterenol infusion, cardiocyclide completely retained the electrophysiological and antiarrhythmic effects. The efficacy of nibentan and sotalol with respect to the repolarization and refractoriness significantly decrease under the conditions of sympathetic nervous system activation. The ability of sotalol to suppress the sinus node function and conduction on the background of isoproterenol infusion is retained.
Kaverina
N V
NV
Laboratory of Circulation System Pharmacology, Institute of Pharmacology, Russian Academy of Medical Sciences, Baltiiskaya Str., 8, Moscow, 125315 Russia.
Lyskovtsev
V V
VV
Popova
E P
EP
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D001549:Benzamides / Q000494:pharmacology*; D002036:Bundle of His / Q000187:drug effects / Q000503:physiopathology; D004285:Dogs; D004562:Electrocardiography / Q000187:drug effects*; D007545:Isoproterenol / Q000494:pharmacology; D009203:Myocardial Infarction / Q000503:physiopathology*; D024661:Potassium Channels, Inwardly Rectifying / Q000037:antagonists & inhibitors; D012032:Refractory Period, Electrophysiological / Q000187:drug effects / Q000502:physiology; D013015:Sotalol / Q000494:pharmacology*
D000318:Adrenergic beta-Agonists; D000889:Anti-Arrhythmia Agents; D001549:Benzamides; D024661:Potassium Channels, Inwardly Rectifying; D013015:Sotalol; D007545:Isoproterenol; C105049:nibentan