Effects of a new class III antiarrhythmic drug nibentan in a canine model of vagally mediated atrial fibrillation

Nibentan, a new class III antiarrhythmic drug, is highly effective in patie nts with atrial flutter and fibrillation. However, its mechanism of action remains unclear. The aim of this study was to investigate the effects of ni bentan using a canine model of vagally sustained atrial fibrillation (AF). Nibentan was intravenously infused to anesthetized open-chest dogs during v agally induced AF. Cumulative doses of nibentan (0.063, 0.125, and 0.250 mg /kg) successfully terminated AF in 78, 88, and 100% as well as prevented AF reinduction in 11, 63, and 90% of cases, respectively. All doses of nibent an significantly and rate-independently increased atrial effective refracto ry period (AERP) with and without vagal stimulation. Activation mapping (22 4 epicardial electrodes) during occurring reentrant wavelets. Herewith the atrial excitation slowed down until conduction failure of reentrant wavelet s led to arrhythmia termination. These changes in activation patterns can b e accounted for by nibentan-induced increase of AERP (55 +/- 9%, 82 +/- 12% , and 90 +/- 6%; p < 0.01) and wavelength for reentry (47 +/- 7%, 68 +/- 12 %, and 72 +/- 4%; p < 0.01) at rapid atrial rates in the presence of vagal stimulation. In conclusion: the high efficacy of nibentan against AF was as sociated with significant rate-independent increase in AERP and in waveleng th, and might be in part explained by block of both delayed rectifier (I-K) and muscarinic I-K.ACh currents.