Antiarrhythmic properties of ivabradine in an experimental model of Short-QT- Syndrome.

Abstract

The If channel inhibitor ivabradine is recommended for treatment of chronic heart failure. However, ivabradine also inhibits human ether-a-go-go (hERG) mediated potassium currents. The aim of the present study was to assess the electrophysiologic effects of ivabradine in an experimental model of short-QT-syndrome. Twelve rabbit hearts were isolated and Langendorff-perfused. After obtaining baseline data, pinacidil, an IK-ATP channel opener, was infused (1 μmol/L). Eight endo- and epicardial monophasic action potentials and a 12-lead ECG showed a significant abbreviation of QT interval (-32 ms, P<.05) and shortening of action potential duration at 90% of repolarization (APD90; -22 ms, P<.05). The shortening of ventricular repolarization was accompanied by a reduction of effective refractory period (ERP; -20 ms, P<.05). Thereafter, hearts were additionally treated with ivabradine (5 μmol/L) leading to an increase of QT interval (+31 ms, P<.05), APD90 (+15 ms, P<.05) as well as of ERP (+38 ms, P<.05) and post-repolarization refractoriness (PRR, +33 ms, P<.05) as compared with sole pinacidil infusion. Under baseline conditions, ventricular fibrillation (VF) was inducible by a standardized pacing protocol including programmed stimulation and burst stimulation in 3 of 12 hearts (6 episodes). After application of 1 μmol/L pinacidil, 6 of 12 hearts were inducible (22 episodes). Additional infusion of 5 μmol/L ivabradine led to a significant suppression of VF. Only two episodes could be induced in 1 of 12 hearts. In the present study ivabradine reversed the electrophysiologic effects of pharmacologically simulated short-QT syndrome. Ivabradine demonstrated antiarrhythmic properties based on an increase of both ERP and PRR.

• Authors: Gerrit Frommeyer, Jan Weller, Christian Ellermann, Sven Kaese, Simon Kochhäuser, Philipp S Lange, Dirk G Dechering, Lars Eckardt
• Journal: Clinical and experimental pharmacology & physiology (Clin Exp Pharmacol Physiol) Vol. 44 Issue 9 Pg. 941-945 (Sep 2017) ISSN: 1440-1681 [Electronic] Australia
• PMID: 28556923 (Publication Type: Journal Article)
• Copyright: © 2017 John Wiley & Sons Australia, Ltd.

Chemical References

• Anti-Arrhythmia Agents
• Benzazepines
• Ivabradine

Topics

• Animals
• Anti-Arrhythmia Agents (pharmacology, therapeutic use)
• Arrhythmias, Cardiac (drug therapy, physiopathology)
• Benzazepines (pharmacology, therapeutic use)
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Ivabradine
• Refractory Period, Electrophysiological (drug effects)
• Ventricular Dysfunction (drug therapy)