The class III antiarrhythmic drugs dofetilide and sotalol prevent AF induction by atrial premature complexes at doses that fail to terminate AF

Background: Clinical trials suggest that sotalol and dofetilide are much mo re effective in preventing atrial fibrillation (AF) than in terminating it. This study evaluated potential mechanisms of discordant sotalol and dofeti lide effects on AF termination vs, prevention. Methods: We applied 240-elec trode epicardial mapping and programmed stimulation in a vagotonic dog mode l of AF before and after dofetilide or sotalol. Results: Under control cond itions, sustained AF could be induced by single S-2 extrastimuli that cause d unidirectional block and macroreentry. Sotalol (2 mg/kg) and dofetilide ( 0.04 mg/kg) failed to terminate AF in any dog, but prevented AF induction b y S-2 stimuli in 19/22 (86%) and 4/5 (80%) of animals, respectively. With s otalol and dofetilide, unidirectional block still occurred, but wavefront r eentry failed. The prevention of S-2-induced reentry was related to large i ncreases in the effective refractory period (ERP) at a BCL of 1000 ms, lead ing to ERPs that exceeded the conduction delay following S-2. Reverse use-d ependent effects resulted in smaller ERP increases at BCLs closer to the AF cycle length. Although the number of zones of reactivation per cycle durin g sustained AF were decreased by sotalol and dofetilide, the changes were s mall and insufficient to terminate AF. Conclusions: Sotalol and dofetilide prevent AF initiation by premature depolarizations at doses that fail to te rminate vagotonic AF, by increasing ERP at the basic cycle length beyond th e associated conduction delay that leads to reentry. (C) 2001 Elsevier Scie nce B.V. All rights reserved.