Antiarrhythmic effect of vernakalant in an experimental model of Long-QT-syndrome.

Abstract

AIMS:

The antiarrhythmic drug vernakalant exerts antiarrhythmic effects in atrial fibrillation. Recent experimental data suggest interactions with the late sodium current and antiarrhythmic effects in ventricular arrhythmias. We aimed at investigating whether treatment with vernakalant reduces polymorphic ventricular tachycardia (VT) in an experimental model of Long-QT-syndrome (LQTS).

METHODS AND RESULTS:

Twenty-nine isolated rabbit hearts were assigned to two groups and treated with erythromycin (300 µM, n = 15) or veratridine (0.5 µM, n = 14) after obtaining baseline data. Thereafter, vernakalant (10 µM) was additionally infused. Infusion of erythromycin or veratridine significantly increased action potential duration (APD90) and QT interval. Erythromycin and veratridine also significantly augmented spatial dispersion of repolarization (erythromycin: +43 ms; veratridine: +55 ms, P < 0.01, respectively) and temporal dispersion of repolarization. After lowering extracellular [K+] in bradycardic hearts, 11 of 15 erythromycin-treated hearts and 4 of 14 veratridine-treated hearts showed early afterdepolarizations and subsequent polymorphic VT. Additional treatment with vernakalant resulted in a significant reduction of spatial dispersion of spatial dispersion in both groups (erythromycin: -32 ms; veratridine: -35 ms, P < 0.05 each) and a stabilization of temporal dispersion. After additional treatment with vernakalant, only 5 of 15 erythromycin-treated hearts (P = 0.07) and 1 of 14 veratridine-treated hearts (P = 0.32) presented polymorphic VT.

CONCLUSION:

Vernakalant has antiarrhythmic effects in this experimental model of acquired LQTS. A reduction of spatial dispersion of repolarization and a stabilization of temporal dispersion in hearts showing polymorphic VT represent the major underlying electrophysiological mechanisms.

• Authors: Gerrit Frommeyer, Catharina Clauss, Christian Ellermann, Harilaos Bogossian, Dirk G Dechering, Simon Kochhäuser, Florian Reinke, Christian Pott, Lars Eckardt
• Journal: Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology (Europace) Vol. 19 Issue 5 Pg. 866-873 (May 01 2017) ISSN: 1532-2092 [Electronic] England
• PMID: 27702859 (Publication Type: Journal Article)
• Copyright: Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: [email protected].

Chemical References

• Anisoles
• Anti-Arrhythmia Agents
• Pyrrolidines
• vernakalant

Topics

• Animals
• Anisoles (administration & dosage)
• Anti-Arrhythmia Agents (administration & dosage)
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Heart Conduction System (drug effects, physiopathology)
• In Vitro Techniques
• Long QT Syndrome (diagnosis, drug therapy, physiopathology)
• Pyrrolidines (administration & dosage)
• Rabbits
• Tachycardia, Ventricular (drug therapy, physiopathology)
• Treatment Outcome