Objectives: This study was designed to evaluate how the atrial electrophysiological and antiarrhythmic effects of azimilide compare Ž . with those of the specific rapid delayed rectifier I blocker dofetilide. Background: Azimilide, a new class III drug, was initially Kr Ž . believed to be a highly selective blocker of the slow delayed rectifier I , but recent studies suggest that azimilide potently blocks I . Ks Kr Thus, it has been suggested that azimilide's in vivo effects may simply be due

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... I blockade. Methods: Dose regimens producing stable Kr Ž . Ž . effects over time were developed, and two dose levels of azimilide 10 and then 20 mgrkg or dofetilide 0.08 and then 0.16 mgrkg Ž . were administered to morphinerchloralose-anesthetized dogs during sustained vagal atrial fibrillation AF . Epicardial mapping was used Ž . to measure conduction velocity and AF cycle length. Results: Azimilide terminated AF in 13r14 dogs 93% , while dofetilide terminated Ž . Ž AF in 6r12 50%, P -0.05 . While dofetilide had strong reverse use-dependent effects on atrial ERP e.g. at lower doses, dofetilide . increased ERP by 51 " 3% at a basic cycle length, BCL, of 400 ms and by 17 " 3% at a BCL of 200 ms , azimilide's effects on ERP Ž . were rate-independent ERP increased at lower dose by 38 " 6%, BCL 400 ms; 35 " 10%, BCL 200 ms . Neither drug affected conduction. Conclusions: Azimilide is effective against experimental AF, and increases ERP with a frequency dependence different from the I blocker dofetilide, suggesting that azimilide's actions on atrial tissue cannot be attributed exclusively to I block, and that effects Kr Kr Ž . on other currents such as I are likely to be important. q 1998 Elsevier Science B.V. Ks