Gerrit Frommeyer1, Jochen Schulze Grotthoff2, Christina Fischer2, Harilaos Bogossian3, Florian Reinke2, Simon Kochhäuser2, Dirk G Dechering2, Michael Fehr4, Peter Milberg2, Lars Eckardt2. 1. Division of Electrophysiology, Department of Cardiovascular Medicine, University of Münster, Münster, Germany. Electronic address: gerrit.frommeyer@ukmuenster.de. 2. Division of Electrophysiology, Department of Cardiovascular Medicine, University of Münster, Münster, Germany. 3. Märkische Kliniken, Department of Cardiology and Angiology, Klinikum Lüdenscheid, University of Witten-Herdecke, Witten-Herdecke, Germany. 4. Clinic of Exotic Pets, Reptiles, and Exotic and Feral Birds, University of Hanover, Hanover, Germany.
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.
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; Henning von der Ahe; Benedict Brücher; Dirk G Dechering; Philipp S Lange; Florian Reinke; Kristina Wasmer; Julia Köbe; Christian Pott; Gerold Mönnig; Lars Eckardt Journal: Naunyn Schmiedebergs Arch Pharmacol Date: 2016-07-12 Impact factor: 3.000