Mechanism of antiarrhythmic action of nibentan on experimental model of vagotonic atrial fibrillation in the canine heart

Effects of a novel class III antiarrhythmic drug nibentan was studied on ca nine model of sustained vagotonic atrial fibrillation (AF) by means of the multielectrodes mapping method (224 unipolar electrodes). Intravenous niben tan (63 mu g/kg) terminated AF in 7 of 9 and prevented reinduction of AF in 1 of 9 dogs. An additional dose of 63 mu g/kg (cumulative dose 125 mu g/kg ) terminated AF in 7 of 8 and prevented AF reinduction in 5 of 8 dogs. An a dditional dose of 125 mu g/kg (cumulative dose 250 mu g/kg, n=3) and single intravenous dose of 250 mu g/kg (n=7) terminated AF in ail dogs and preven ted AF reinduction in 9 of 10 dogs. Atrial activation mapping shelved that the drug terminated AF by reducing the number and increasing the size of re entry circuits, leading to termination by mechanisms related to block in re maining circuits. These changes accounted for nibentan-induced increase of atrial effective refractory period (AERP) and wavelength (WL). So, at rapid atrial pacing rates and in the presence of vagal stimulation all doses of nibentan (63, 125 and 250 mu g/kg) significantly increased AERP by 55+/-9, 82+/-12, 90+/-6% and WL by 47+/-7, 68+/-12, 72+/-4% from control values, re spectively.