Nibentan prevents atrial fibrillation caused by acetylcholine injection into the sinus node artery of the dog heart in situ

Effects of a new class III antiarrhythmic drug nibentan were studied in a m odel of atrial fibrillation (AF) induced by acetylcholine (ACh) injection i nto the sinus node artery (SNA) of the dog heart (n=6). Nibentan was inject ed intravenously at a dose of 0,25 mg/kg. before nibentan treatment, ACh in jection (7,1+/-4,8 mu M/l, 1 ml, n=3, for each dog) into the SNA always cau sed AF, but after nibentan treatment, ACh injection was not able to cause A F in 94% of cases (p<0,001). Atrial activation mapping of right atrium (112 unipolar electrodes) showed that drug prevented development of reentrant A F by mechanisms related to: 1) disappearance of provocative extrasystolic b eats, 2) or in the presence of extrasystolic beats, rapid conduction block of remaining reentry circuits, leading to AF termination. These antiarrhyth mic effects of nibentan can be caused by significant increase of atrial eff ective refractory period and wavelength (at rapid atrial pacing) by 63+/-12 % and 52+/-8%, respectively, as well as by direct anticholinergic action of nibentan.