Effects of E047/1, a new antiarrhythmic drug, on experimental atrial fibrillation in anesthetized dogs.

Abstract

Effects of a new antiarrhythmic drug, E047/1, on atrial fibrillation were studied. Atrial conduction velocity and effective refractory period (ERP), electrocardiogram parameters (RR, PR, QRS, QT, and QTc intervals), systolic and diastolic blood pressure, and plasma concentrations of E047/1 were determined during the first 30 min after sequential administration of 1, 3, and 6 mg/kg of E047/1 in polysorbate 60 (Tween 60) to anesthetized, opened-chest dogs with vagally induced atrial fibrillation. Epicardial mapping (using 224 unipolar electrodes) was used to determine atrial fibrillation cycle length and activation sequence before and after drug administration. E0471, 3 mg/kg, prevented atrial fibrillation reinduction, and 6 mg/kg terminated atrial fibrillation. E047/1, 6 mg/kg, increased atrial ERP from 124 +/- 9 to 168 +/- 14 ms (p < 0.05). Conduction velocity decreased from 103 +/- 4 cm/s to 87 +/- 3 cm/s (p < 0.05). Epicardial mapping showed that under drug influence there was gradual reduction of wavelet number until termination of the reentrant excitation. Atrial fibrillation cycle length increased before atrial fibrillation termination from 93 +/- 4 to 137 +/- 12 ms (p < 0.05). The ability of E047/1 to terminate and prevent reinduction of experimental atrial fibrillation appears associated more with a significant prolongation of the atrial ERP than with a slowing of conduction. E047/1 appears to be a promising antifibrillatory agent.