Effects of S-1389 (711389-S), a new antiarrhythmic agent, on the conduction in perfused guinea pig hearts

In the His bundle and ventricular electrograms of Langendorff-perfused guinea pig hearts driven at a cycle length of 450 or 700 msec, S-1389 (711389-S), a new antiarrhythmic agent, above 3 x 10(-7) or 10(-6) M increased the basal conduction times in the following order: His-Purkinje system greater than ventricular and atrial muscles greater than atrioventricular (AV) node. Slowing of the ventricular and AV nodal conduction of extrasystoles with variable coupling intervals was also caused by S-1389. S-1389 above 10(-6) or 3 x 10(-6) M significantly prolonged the functional and/or effective refractory periods of the AV node and ventricle. Disopyramide (3 x 10(-6)-3 x 10(-5) M) also produced similar effects, but they were much less potent than those of S-1389. Although disopyramide did not produce the rate-dependent increases in the atrial and AV nodal conduction times and in the AV nodal refractory period, S-1389 increased these parameters rate-dependently.