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.