Please use this identifier to cite or link to this item: https://hdl.handle.net/2440/116823
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Type: Journal article
Title: Antiarrhythmic effect of vernakalant in electrically remodeled goat atria is caused by slowing of conduction and prolongation of postrepolarization refractoriness
Author: Van Hunnik, A.
Lau, D.
Zeemering, S.
Kuiper, M.
Verheule, S.
Schotten, U.
Citation: Heart Rhythm, 2016; 13(4):964-972
Publisher: Elsevier
Issue Date: 2016
ISSN: 1547-5271
1556-3871
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Responsibility: 
Arnevan Hunnik, Dennis H.Lau, Stef Zeemering, Marion Kuiper, Sander Verheule, Ulrich Schotten
Abstract: Vernakalant inhibits several potassium currents and causes a rate- and voltage-dependent inhibition of the sodium current.The aim of this study was to evaluate the antiarrhythmic mechanism of vernakalant in normal and electrically remodeled atria.Fourteen goats were instrumented with electrodes on both atria. Drug effects on refractory period (ERP), conduction velocity (CV), and atrial fibrillation cycle length (AFCL) were determined in normal goats (control) and after 2 (2dAF) or 11 (11dAF) days of pacing-induced atrial fibrillation (AF) in awake goats. To evaluate the contribution of changes in conduction and ERP, the same experiments were performed with flecainide and AVE0118. In a subset of goats, monophasic action potentials were recorded during anesthesia.Vernakalant dose-dependently prolonged ERP and decreased CV in CTL experiments. Both effects were maintained after 2dAF and 11dAF. After 11dAF, conduction slowed down by 8.2 ± 1.5 cm/s and AFCL increased by 55 ± 3 ms, leading to AF termination in 5 out of 9 goats. Monophasic action potential measurements revealed that ERP prolongation was due to enhanced postrepolarization refractoriness. During pacing, vernakalant had comparable effects on CV as flecainide, while effect on ERP was comparable to AVE0118. During AF, all compounds had comparable effects on median AFCL and ERP despite differences in their effects on CV during pacing.The antiarrhythmic effect of vernakalant in the goat, at clinically relevant plasma concentrations, is based on both conduction slowing and ERP prolongation due to postrepolarization refractoriness. These electrophysiological effects were not affected by long-term electrical remodeling of the atria.
Keywords: Vernakalant; atrial fibrillation; remodeling; antiarrhythmic drugs; in vivo model; flecainide; AVE0118
Rights: © 2016 Heart Rhythm Society. All rights reserved.
DOI: 10.1016/j.hrthm.2015.12.009
Published version: http://dx.doi.org/10.1016/j.hrthm.2015.12.009
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