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Further insights into the underlying electrophysiological mechanisms for reduction of atrial fibrillation by ranolazine in an experimental model of chronic heart failure.
MedLine Citation:
PMID:  23099358     Owner:  NLM     Status:  Publisher    
AIMS: Ranolazine (RAN) was reported to be effective and safe in converting atrial fibrillation (AF) to sinus rhythm by administration of a single dose ('pill in the pocket') to patients with structural heart disease. This study examines the underlying mechanisms for the antiarrhythmic benefit of RAN application in chronic heart failure (CHF). METHODS AND RESULTS: In 10 female rabbits, CHF was induced by rapid ventricular pacing, leading to a significant decrease in ejection fraction in the presence of a dilated left ventricle and atrial enlargement. Twelve rabbits were sham-operated and served as controls. Isolated hearts were perfused using the Langendorff method. Burst pacing was used to induce AF. Monophasic action potential recordings showed an increase of atrial action potential duration (aAPD) and effective refractory period (aERP) in CHF hearts compared with sham hearts. Infusion of acetylcholine (1 µM) and isoproterenol (1 µM) led to AF in all failing hearts and in 11 sham hearts. Simultaneous infusion of RAN (10 µM) remarkably reduced inducibility of AF in 50% of sham and 50% of failing hearts. RAN had no effect on aAPD but significantly increased aERP, leading to a marked increase in atrial post-repolarization refractoriness. Moreover, RAN application moderately increased interatrial conduction time. CONCLUSION: RAN has been shown to be effective in reducing the inducibility of AF in an experimental model of AF. The antiarrhythmic effect is mainly due to development of atrial post-repolarization refractoriness and a moderate increase in conduction time. The described electrophysiological mechanisms remain preserved in the setting of CHF.
Gerrit Frommeyer; Marco Schmidt; Catharina Clauß; Sven Kaese; Jörg Stypmann; Christian Pott; Lars Eckardt; Peter Milberg
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-10-25
Journal Detail:
Title:  European journal of heart failure     Volume:  -     ISSN:  1879-0844     ISO Abbreviation:  Eur. J. Heart Fail.     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-10-26     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100887595     Medline TA:  Eur J Heart Fail     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Division of Electrophysiology, Department of Cardiovascular Medicine, University Hospital of Münster, Germany.
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