Atypical Antiadrenergic Effect of Refralon as a Mechanism of High Antiarrhythmic Effectiveness

We studied the effect of Refralon on the electrophysiological properties of the supraventricular myocardium against the background of adrenergic (epinephrine) influence in the zone of the pulmonary veins, the area where 50-90% of atrial arrhythmias is triggered. The experiments were carried out on isolated tissue preparations of Wistar rats. The multichannel microelectrode array technique was used to record action potentials simultaneously in the atrium and in the ostium and distal parts of the pulmonary veins. Epinephrine application (12-50 nM) led to depolarization of the resting potential and the conduction block in the distal part of the pulmonary veins. Refralon (30 μg/kg) restored the resting potential in the distal part of the pulmonary veins. Against the background of epinephrine, Refralon did not significantly change the duration of the action potential at 90% repolarization in comparison with control. At the same time, the comparison drug E-4031 against the background of epinephrine significantly increased the duration of action potential in the atrium and in the ostium of the pulmonary veins, and sotalol increased it only in the ostium. Neither E-4031, nor sotalol restored conduction in their distal part. Refralon has a biphasic effect under conditions of adrenergic stimulation: the fast component is responsible for stabilizing the resting potential in the pulmonary vein and reduces the dispersion of action potential duration in the atrium and pulmonary vein and is also quickly washed away, and the slow component is responsible for the increase of the action potential duration and is slowly washed away.