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 × 10-7 or 10-6 M increased the basal conduction times in the following order: His-Purkinje system>ventricular and atrial muscles> 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 × 10-6 M significantly prolonged the functional and/or effective refractory periods of the AV node and ventricle. Disopyramide (3×10-6-3×10-5M) 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