IS CYCLIC-AMP INVOLVED IN THE DEFIBRILLATING EFFECT OF SOTALOL

Ventricular fibrillation induced in animals pretreated with sotalol, a class III antiarrhythmic agent, would spontaneously terminate and rev ert into a sinus rhythm. This phenomenon has been atributed to the cla ss III action of this drug, prolongation of myocardial action potentia l duration and effective refractory period. Since various observations suggested that these alone cannot explain the defibrillating phenomen on, we hypothesised that sotalol affeced ventricular intercellular syn chronization by increasing intercellular coupling. Our recent experime ntal studies have shown that sotalol antagonized the cellular decoupli ng to guinea pig ventricular muscle strip caused by perfusion with eit her a hypoxic normal Tyrode's solution or an oxygenated high Ca2+ Tyro de's solution. We assumed that the most likely mechanism for the resto ration of intercellular coupling would be by increasing intracellular cAMP concentration. In order to test this hypothesis, we studied the m odification of this sotalol-induced recoupling by a cAMP dependent pro tein kinase inhibitor. The results clearly supported our assumption si nce the addition of Arg-Gly-Tyr-Ala-Leu-Gly (pure A- kinase inhibitor) prevented the aforementioned cellular recoupling action of sotalol in a dose-dependent manner. It can thus be concluded that changes in int racellular cAMP level are involved in the synchronizing/defibrillating effect of sotalol.