1. Electrophysiological profile of vernakalant in an experimental whole-heart model: the absence of proarrhythmia despite significant effect on myocardial repolarization.
- Author
-
Frommeyer G, Milberg P, Clauss C, Schmidt M, Ramtin S, Kaese S, Grundmann F, Grotthoff JS, Pott C, and Eckardt L
- Subjects
- Acetanilides toxicity, Action Potentials, Animals, Arrhythmias, Cardiac diagnosis, Arrhythmias, Cardiac physiopathology, Heart Conduction System physiopathology, In Vitro Techniques, Models, Animal, Perfusion, Piperazines toxicity, Potassium Channel Blockers toxicity, Rabbits, Ranolazine, Risk Assessment, Risk Factors, Sodium Channel Blockers toxicity, Sotalol toxicity, Time Factors, Anisoles toxicity, Anti-Arrhythmia Agents toxicity, Arrhythmias, Cardiac chemically induced, Electrophysiologic Techniques, Cardiac, Heart Conduction System drug effects, Pyrrolidines toxicity
- Abstract
Aim: The most recent European Society of Cardiology (ESC) update on atrial fibrillation has introduced vernakalant (VER) for pharmacological cardioversion of atrial fibrillation. The aim of the present study was to investigate the safety profile of VER in a sensitive model of proarrhythmia., Methods and Results: In 36 Langendorff-perfused rabbit hearts, VER (10, 30 µM, n = 12); ranolazine (RAN, 10, 30 µM, n = 12), or sotalol (SOT, 50; 100 µM, n = 12) were infused after obtaining baseline data. Monophasic action potentials and a 12-lead electrocardiogram showed a significant QT prolongation after application of VER as compared with baseline (10 µM: +25 ms, 30 µM: +50 ms, P < 0.05) accompanied by an increase of action potential duration (APD). The increase in APD90 was accompanied by a more marked increase in effective refractory period (ERP) leading to a significant increase in post-repolarization refractoriness (PRR, 10 µM: +30 ms, 30 µM: +36 ms, P < 0.05). Vernakalant did not affect the dispersion of repolarization. Lowered potassium concentration in bradycardic hearts did not provoke early afterdepolarizations (EADs) or polymorphic ventricular tachycardia (pVT). Comparable results were obtained with RAN. Hundred micromolars of SOT led to an increase in QT interval (+49 ms) and APD90 combined with an increased ERP and PRR (+23 ms). In contrast to VER, 100 µM SOT led to a significant increase in dispersion of repolarization and to the occurrence of EAD in 10 of 12 and pVT in 8 of 12 hearts., Conclusion: In the present study, application of VER and SOT led to a comparable prolongation of myocardial repolarization. Both drugs increased the PRR. However, VER neither affect the dispersion of repolarization nor induce EAD and therefore did not cause proarrhythmia., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.)
- Published
- 2014
- Full Text
- View/download PDF