Vernakalant in an experimental model of pacing-induced heart failure: lack of proarrhythmia despite prolongation of repolarization.

Abstract

BACKGROUND:

The present ESC guidelines on atrial fibrillation have introduced vernakalant (VER) for pharmacologic cardioversion of atrial fibrillation. The aim of the present study was to investigate possible proarrhythmic effects of vernakalant in an experimental model of heart failure (HF).

METHODS AND RESULTS:

In 12 female rabbits, HF was induced with the use of 4 weeks of rapid ventricular pacing. Twelve rabbits were sham operated. Isolated hearts demonstrated a significant prolongation of myocardial repolarization after induction of HF. Vernakalant caused a concentration-dependent (10 μmol/L and 30 μmol/L) increase of action potential duration (APD90) and QT interval without affecting spatial and temporal dispersion of repolarization. The increase in APD90 was accompanied by a greater increase in refractory period resulting in a significant increase in post-repolarization refractoriness. In control conditions, programmed ventricular stimulation and burst pacing led to ventricular fibrillation (VF) in 2 of the 12 sham (4 episodes) and in 3 of the 12 HF (24 episodes) subjects. In the presence of 30 μmol/L vernakalant, VF was no longer inducible in both groups (0 episodes). In the presence of low K+ concentration, neither sham nor HF vernakalant-treated subjects developed early after-depolarizations or ventricular tachyarrhythmias.

CONCLUSION:

In the present study, application of vernakalant led to a significant prolongation of myocardial repolarization and increased post-repolarization refractoriness but did not induce early after-depolarization and therefore did not cause proarrhythmia in failing hearts.

• Authors: Gerrit Frommeyer, Jochen Schulze Grotthoff, Christina Fischer, Harilaos Bogossian, Florian Reinke, Simon Kochhäuser, Dirk G Dechering, Michael Fehr, Peter Milberg, Lars Eckardt
• Journal: Journal of cardiac failure (J Card Fail) Vol. 20 Issue 10 Pg. 786-792 (Oct 2014) ISSN: 1532-8414 [Electronic] United States
• PMID: 25084217 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Inc. All rights reserved.

Chemical References

• Anisoles
• Anti-Arrhythmia Agents
• Pyrrolidines
• vernakalant

Topics

• Animals
• Anisoles (pharmacology)
• Anti-Arrhythmia Agents (pharmacology)
• Atrial Fibrillation (diagnosis, drug therapy, etiology)
• Cardiac Resynchronization Therapy (adverse effects)
• Disease Models, Animal
• Electrocardiography
• Female
• Heart Conduction System (drug effects)
• Heart Failure (etiology, physiopathology)
• Heart Ventricles (pathology, physiopathology)
• Models, Cardiovascular
• Pyrrolidines (pharmacology)
• Rabbits