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

Effects of a new antiarrhythmic drug, E047/1, on atrial fibrillation were s tudied. Atrial conduction velocity and effective refractory period (ERP), e lectrocardiogram parameters (RR, PR, QRS. QT, and QTc intervals), systolic and diastolic blood pressure, and plasma concentrations of E047/1 were dete rmined 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-che st dogs with vagally induced atrial fibrillation. Epicardial mapping (using 224 unipolar electrodes) was used to determine atrial fibrillation cycle l ength 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 t o 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 i nfluence there was gradual reduction of wavelet number until termination of the reentrant excitation. Atrial fibrillation cycle length increased befor e atrial fibrillation termination from 93 +/- 4 to 137 +/- 12 ms (p < 0.05) . The ability of E047/1 to terminate and prevent reinduction of experimenta l atrial fibrillation appears associated more with a significant prolongati on of the atrial ERP than with a slowing of conduction. E047/1 appears to b e a promising antifibrillatory agent.