Consequences of atrial electrical remodeling for the anti-arrhythmic action of class IC and class III drugs

Objective: Atrial fibrillation (AF) induces electrical and ionic remodeling of the atria. We investigated whether AF-induced remodeling alters the electrophysiological and anti-fibrillatory effects of class I (flecamide) and class III (D-sotalol, ibutilide) anti-arrhythmic drugs. Methods: In 9 goats, the effects of flecainide (6 mg/kg) and D-sotalol (6 mg/kg) on atrial electrophysiology were measured both before and after 48 h of electrically induced AF. During a 1-h infusion period the atrial effective refractory period (AERP) and conduction velocity (CV) were measured both during slow and rapid pacing (interval 400 and 200 ms). In 8 other goats, the rate-dependent effects of ibutilide (0.12 mg/kg) on AERP were determined. Results: The effects of flecainide on atrial conduction and refractoriness were not altered after 48 h of AF. At a dose of 6 mg/kg flecainide reduced the CV200 by 19 +/- 5% in nomial atria and by 21 +/- 9% after 48 h of AF (p = 0.20). The AERP200 was prolonged by 10 +/- 6% and 8 +/- 7%, respectively (p = 0.40). In contrast, the effect Of D-sotalol on atrial refractoriness was markedly diminished. During control D-sotalol prolonged the AERP400 by 17 6% compared to only 6 +/- 5% after 2 days of AF (p < 0.01). Also ibutilide lost much of its class III effect on the AERP by electrical remodeling (from 15 to 5%; p < 0.05). The loss of class III action was less pronounced at rapid heart rates. Conclusions: AF-induced atrial electrical remodeling in the goat did not modulate the action of flecamide on atrial conduction and refractoriness. In contrast, the class III effects of D-sotalol and ibutilide on the atria were, strongly reduced after 2 days of AF. The prolongation of QT-duration was not affected. (c) 2005 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.