Reduced Ventricular Proarrhythmic Potential of the Novel Combined Ion-Channel Blocker AZD1305 Versus Dofetilide in Dogs With Remodeled Hearts

Daniel M. Johnson, Monique M. J. de Jong, Harry J. G. M. Crijns, Leif G. Carlsson, Paul G. A. Volders*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

14 Citations (Web of Science)

Abstract

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
Original languageEnglish
Pages (from-to)201-U328
JournalCirculation-Arrhythmia and Electrophysiology
Volume5
Issue number1
DOIs
Publication statusPublished - Feb 2012

Keywords

  • antiarrhythmic drugs
  • ion channels
  • remodeling
  • torsade de pointes

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