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

doi:10.1161/CIRCEP.111.963025

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 journal › Article › Academic › peer-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 language	English
Pages (from-to)	201-U328
Journal	Circulation-Arrhythmia and Electrophysiology
Volume	5
Issue number	1
DOIs	https://doi.org/10.1161/CIRCEP.111.963025
Publication status	Published - Feb 2012

Keywords

antiarrhythmic drugs
ion channels
remodeling
torsade de pointes

Access to Document

10.1161/CIRCEP.111.963025

Cite this

@article{8e9efb3d3d9a446d95467fb4718d3a5c,

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

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",

keywords = "antiarrhythmic drugs, ion channels, remodeling, torsade de pointes",

author = "Johnson, {Daniel M.} and {de Jong}, {Monique M. J.} and Crijns, {Harry J. G. M.} and Carlsson, {Leif G.} and Volders, {Paul G. A.}",

year = "2012",

month = feb,

doi = "10.1161/CIRCEP.111.963025",

language = "English",

volume = "5",

pages = "201--U328",

journal = "Circulation-Arrhythmia and Electrophysiology",

issn = "1941-3149",

publisher = "LIPPINCOTT WILLIAMS & WILKINS",

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Reduced Ventricular Proarrhythmic Potential of the Novel Combined Ion-Channel Blocker AZD1305 Versus Dofetilide in Dogs With Remodeled Hearts. / Johnson, Daniel M.; de Jong, Monique M. J.; Crijns, Harry J. G. M. et al.

In: Circulation-Arrhythmia and Electrophysiology, Vol. 5, No. 1, 02.2012, p. 201-U328.

Research output: Contribution to journal › Article › Academic › peer-review

TY - JOUR

T1 - Reduced Ventricular Proarrhythmic Potential of the Novel Combined Ion-Channel Blocker AZD1305 Versus Dofetilide in Dogs With Remodeled Hearts

AU - Johnson, Daniel M.

AU - de Jong, Monique M. J.

AU - Crijns, Harry J. G. M.

AU - Carlsson, Leif G.

AU - Volders, Paul G. A.

PY - 2012/2

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AB - 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

KW - antiarrhythmic drugs

KW - ion channels

KW - remodeling

KW - torsade de pointes

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