Reduced Ventricular Proarrhythmic Potential of the Novel Combined Ion-Channel Blocker AZD1305 Versus Dofetilide in Dogs With Remodeled Hearts
| Autor: | Harry J.G.M. Crijns, Paul G.A. Volders, Daniel M. Johnson, Monique M.J. de Jong, Leif G. Carlsson |
|---|---|
| Přispěvatelé: | Cardiologie, MUMC+: MA Cardiologie (9), CTC, RS: CARIM School for Cardiovascular Diseases |
| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
Male
medicine.medical_specialty medicine.medical_treatment Dofetilide Torsades de pointes Antiarrhythmic agent QT interval Dogs Heart Rate antiarrhythmic drugs Physiology (medical) Internal medicine Phenethylamines Potassium Channel Blockers medicine Animals Repolarization Atrioventricular Block remodeling Sulfonamides Ventricular Remodeling business.industry ion channels Potassium channel blocker medicine.disease Disease Models Animal Treatment Outcome Anesthesia Cardiology Female torsade de pointes Carbamates Electrophysiologic Techniques Cardiac Cardiology and Cardiovascular Medicine business Azabicyclo Compounds Atrioventricular block Ion channel blocker Follow-Up Studies medicine.drug |
| Zdroj: | Circulation-Arrhythmia and Electrophysiology, 5(1), 201-U328. LIPPINCOTT WILLIAMS & WILKINS |
| ISSN: | 1941-3149 |
| Popis: | Background— AZD1305 is an investigational antiarrhythmic agent for management of atrial fibrillation. It blocks various cardiac ion currents at different potencies and has atrial-predominant electrophysiological effects. We investigated the electrophysiological and proarrhythmic effects of AZD1305 versus dofetilide in dogs with chronic complete atrioventricular block and myocardial hypertrophic remodeling. Methods and Results— AZD1305 was administered to anesthetized mongrel dogs before and >2 weeks after the induction of atrioventricular block and ventricular and atrial electrophysiological parameters were assessed. In all dogs, the selective I Kr blocker dofetilide was used to examine susceptibility to acquired torsades de pointes in chronic atrioventricular block and for comparison. At normal sinus rhythm, AZD1305 increased QT and RR intervals from 290±7 to 397±15 ms (+37%, P P =0.002), respectively. In the same animals at chronic atrioventricular block, AZD1305 increased the QT interval from 535±28 to 747±36 ms (+40%, P P P P =0.20) despite similar left-ventricular monophasic-action-potential duration prolongations. Conclusions— Despite causing similar degrees of repolarization delay as the selective I Kr blocker dofetilide, the combined ion-channel blocker AZD1305 induces less repolarization instability and has a lower ventricular proarrhythmic potential in the remodeled dog heart. |
| Databáze: | OpenAIRE |
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