Antiarrhythmic Effect of Ranolazine in Combination with Selective NCX-Inhibition in an Experimental Model of Atrial Fibrillation
Open Access
- 20 October 2020
- journal article
- research article
- Published by MDPI AG in Pharmaceuticals
- Vol. 13 (10), 321
- https://doi.org/10.3390/ph13100321
Abstract
The aim of this study was to investigate the effects of a combination of ranolazine with different selective inhibitors of the Na+/Ca2+-exchanger (NCX) in an established experimental model of atrial fibrillation (AF). Eighteen hearts of New Zealand white rabbits were retrogradely perfused. Atrial catheters were used to record monophasic action potentials (aPRR). Hearts were paced at three different cycle lengths. Thereby, atrial action potential durations (aAPD90), atrial effective refractory periods (aERP) and atrial post-repolarization refractoriness were obtained. Isoproterenol and acetylcholine were employed to increase the occurrence of AF. Thereafter, the hearts were assigned to two groups (n = 9 each group) and additionally perfused with a combination of 10 µM ranolazine and 1 µM of the selective NCX-inhibitor ORM-10103 (group A: Rano-ORM) or 10 µM ranolazine and 1 µM of another NCX-inhibitor, SEA0400 (group B: Rano-SEA). The infusion of Iso/ACh led to a shortening of aAPD90, aERP, aPRR and the occurrence of AF episodes was significantly increased. Additional perfusion with ranolazine and ORM-10103 (group A) significantly prolonged the refractory periods and aPRR and AF episodes were effectively reduced. In group B, Rano-SEA led to a slight decrease in aAPD90 while aERP and aPRR were prolonged. The occurrence of AF episodes was consecutively reduced. To our knowledge, this is the first study investigating the effect of ranolazine combined with different selective NCX-inhibitors in an isolated whole-heart model of AF. Both combinations prolonged aERP and aPRR and thereby suppressed the induction of AF.This publication has 28 references indexed in Scilit:
- Antiarrhythmic Properties of Ranolazine: Inhibition of Atrial Fibrillation Associated TASK-1 Potassium ChannelsFrontiers in Pharmacology, 2019
- Mechanisms by Which Ranolazine Terminates Paroxysmal but Not Persistent Atrial FibrillationCirculation: Arrhythmia and Electrophysiology, 2019
- Antiarrhythmic Effects of Combining Dofetilide and Ranolazine in a Model of Acutely Induced Atrial Fibrillation in HorsesJournal of Cardiovascular Pharmacology, 2018
- Triggered activity in atrial myocytes is influenced by Na+/Ca2+ exchanger activity in genetically altered miceJournal of Molecular and Cellular Cardiology, 2016
- New antiarrhythmic targets in atrial fibrillationFuture Cardiology, 2015
- Antiarrhythmic properties of ranolazine: A review of the current evidenceInternational Journal of Cardiology, 2015
- Antiarrhythmic Effect of Ranolazine in Combination with Class III Drugs in an Experimental Whole-Heart Model of Atrial FibrillationCardiovascular Therapeutics, 2013
- Further insights into the underlying electrophysiological mechanisms for reduction of atrial fibrillation by ranolazine in an experimental model of chronic heart failureEuropean Journal of Heart Failure, 2012
- Comparison of Effectiveness and Safety of Ranolazine Versus Amiodarone for Preventing Atrial Fibrillation After Coronary Artery Bypass GraftingThe American Journal of Cardiology, 2011
- Pharmacological Rhythm and Rate Control Treatment for Atrial FibrillationThe Patient - Patient-Centered Outcomes Research, 2010