ELECTROPHYSIOLOGIC AND HEMODYNAMIC-EFFECTS OF H-234/09 (ALMOKALANT), QUINIDINE, AND (+)-SOTALOL IN THE ANESTHETIZED DOG

The electrophysiologic and hemodynamic effects of H 234/09 (Almokalant), a novel class III antiarrhythmic agent, were studied in the anesthetized dog. H 234/09 (1.0-mu-mol/kg i.v.) significantly prolonged the atrial and ventricular effective refractory periods, the ventricular monophasic action potential duration, and the paced QT interval. At this dose, atrial, ventricular, and atrioventricular conduction was not affected, aortic blood pressure was not changed, and contractile force was transiently increased. The effects on cardiac repolarization and refractoriness induced by H 234/09 were both larger and more long lasting than the effects observed after quinidine (11.8-mu-mol/kg) and (+)-sotalol (9.7-mu-mol/kg). However, both quinidine and (+)-sotalol significantly reduce the aortic blood pressure and (+)-sotalol also decreased cardiac contractility. The effect of H 234/09 on atrial refractoriness was very little influenced by the paced heart rate and was twice as large as the corresponding effect in the ventricle. In conclusion, H 234/09 has electrophysiological properties suggestive of a class III antiarrhythmic. H 234/09 may have a favorable therapeutic profile compared to both quinidine and (+)-sotalol, especially for the treatment of atrial arrhythmias.