Effect of sotalol, aprindine and their combination on maximum upstroke velocity of action potential in guinea-pig papillary muscle.

Microelectrode experiments were performed on papillary muscle of 11 guinea-pigs at driven heart rates of 60 and 120 b.p.m. to study the effect of sotalol 10(-4) M, aprindine 10(-6) M and the combination of both on Vmax, action potential duration and effective refractory period. Only sotalol exerted tonic Vmax block. Aprindine, sotalol and their combination produced an increase in phasic, combined tonic and phasic, and in steady state Vmax block: the effect of the combination on these parameters being larger than the effect of the single agents alone. Action potential duration was lengthened by both drugs and their combination. A statistically significant increase in effective refractory period was observed for sotalol and the combination sotalol-aprindine but not for aprindine. It can be concluded that simultaneous application of sotalol and aprindine enhances phasic, combined tonic and phasic, and steady state Vmax block with an unchanged effect of sotalol on repolarization. The effect of combinations can be explained on the basis of competition for the same receptor in the Na+ channel.