Document Detail


Effect of ranolazine on ventricular repolarization in class III antiarrhythmic drug-treated rabbits.
MedLine Citation:
PMID:  23044390     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
BACKGROUND: Ranolazine exhibits a synergistic effect in combination with class III drugs to suppress atrial fibrillation. OBJECTIVE: To investigate whether a combination therapy affects repolarization and provokes ventricular tachyarrhythmias (VT) in a sensitive model of proarrhythmia. METHODS: Thirty-seven rabbits were assigned to 3 groups and fed with amiodarone (50 mg/kg/d; n = 10) or dronedarone (50 mg/kg/d; n = 10) over a period of 6 weeks. A third group was used as control (n = 17). After obtaining baseline data in Langendorff-perfused control hearts, sotalol (100 μM) was administered in this group. Thereafter, ranolazine (10 μM) was additionally infused on top of amiodarone, dronedarone, or sotalol. RESULTS: Chronic treatment with amiodarone or dronedarone as well as sotalol significantly increased action potential duration at 90% repolarization (APD(90)). Additional treatment with ranolazine further increased APD(90) in amiodarone- and dronedarone-pretreated hearts but not in sotalol-treated hearts. Ranolazine increased postrepolarization refractoriness as compared with amiodarone or dronedarone alone owing to a marked effect on the refractory period. In contrast to amiodarone and dronedarone, acute application of sotalol increased dispersion of repolarization (P < .05). Additional treatment with ranolazine did not further increase spatial or temporal dispersion. After lowering extracellular [K(+)] in bradycardic hearts, no proarrhythmia occurred in amiodarone- or dronedarone-treated hearts whereas 11 of 17 sotalol-treated hearts showed early afterdepolarizations and subsequent polymorphic VT. Additional treatment with ranolazine reduced the number of VT episodes in sotalol-treated hearts and did not cause proarrhythmia in combination with amiodarone or dronedarone. CONCLUSIONS: Application of ranolazine on top of class III drugs does not cause proarrhythmia despite a marked effect on ventricular repolarization. The effect of ranolazine on the repolarization reserve is associated with the lack of effect on early afterdepolarizations and dispersion of repolarization.
Authors:
Gerrit Frommeyer; Dennis Kaiser; Timo Uphaus; Sven Kaese; Nani Osada; Sridharan Rajamani; Luiz Belardinelli; Günter Breithardt; Lars Eckardt; Peter Milberg
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-8-28
Journal Detail:
Title:  Heart rhythm : the official journal of the Heart Rhythm Society     Volume:  -     ISSN:  1556-3871     ISO Abbreviation:  Heart Rhythm     Publication Date:  2012 Aug 
Date Detail:
Created Date:  2012-10-9     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101200317     Medline TA:  Heart Rhythm     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2012 The Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.
Affiliation:
Division of Clinical and Experimental Electrophysiology, Department of Cardiology and Angiology, and.
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