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Efficacy of Azimilide and Dofetilide in the Dog Right Atrial Enlargement Model of Atrial Flutter
Author(s) -
RESTIVO MARK,
HEGAZY MAHA,
ELHAMAMI MOUSTAFA,
YIN HONG,
CAREF EDWARD B.,
ASSADI MAHSHID A.,
BROOKS ROBERT R.,
ELSHERIF NABIL
Publication year - 2001
Publication title -
journal of cardiovascular electrophysiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.193
H-Index - 138
eISSN - 1540-8167
pISSN - 1045-3873
DOI - 10.1046/j.1540-8167.2001.01018.x
Subject(s) - dofetilide , atrial flutter , medicine , cardiology , flutter , anesthesia , torsades de pointes , refractory period , atrial fibrillation , qt interval , engineering , aerodynamics , aerospace engineering
Azimilide and Dofetilide Atrial Flutter Efficacy.Introduction: Azimilide dihydrochloride blocks both the rapid (I Kr ) and slow (I Ks ) components of the delayed rectified K + current; dofetilide blocks only I Kr . Their efficacies were assessed on atrial flutter reentrant circuits in dogs with surgically induced right atrial enlargement. Methods and Results: Multiple biopsies of the tricuspid valve and banding of the pulmonary artery in male mongrel dogs made them susceptible, about 3 weeks postoperatively, to stimulation‐induced sustained (5 min or longer) atrial flutter. Azimilide 3 mg/kg administered intravenously (IV) terminated flutter in 8 of 8 dogs, but a slower, nonsustained arrhythmia could be reinduced in 5. In these 5 dogs, azimilide 10 mg/kg terminated flutter and prevented reinduction. This dose increased effective refractory period significantly more in the slow conduction zone (25%) than in the normal zone (17%) and increased flutter cycle length (37%). Termination followed progressive conduction delay in the slow zone of the reentrant circuit. Dofetilide 1 μg/kg IV terminated flutter in 6 of 6 dogs, but the arrhythmia could be reinduced. At 3 μg/kg, flutter terminated in all dogs and could not be reinduced. Dofetilide also increased the effective refractory period significantly more in the slow zone (17%) than in the normal zone (12%) and increased cycle length (33%), leading to interruption of the arrhythmia circuit. Conclusion: In the canine right atrial enlargement model of circus movement atrial flutter, both azimilide 10 mg/kg IV and dofetilide 3 μg/kg IV were 100% effective in terminating flutter and preventing reinduction. Efficacy relied on a similar mechanism of differentially prolonged refractoriness in the slow conduction component of the reentrant circuit where drug‐induced termination occurred.