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Electrophysiologic profile of dronedarone on the ventricular level: beneficial effect on post-repolarization refractoriness in the presence of rapid phase-III-repolarization.
MedLine Citation:
PMID:  21964157     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
BACKGROUND: Dronedarone (D) is developed to maintain sinus rhythm in patients suffering from atrial fibrillation. The aim of the present study was to investigate, whether dronedarone also has an antiarrhythmic potential in the ventricle and to elucidate the mechanisms for its low proarrhythmic potential in an experimental whole heart model. METHODS AND RESULTS: 35 rabbits underwent chronic treatment with D (n=15; 50mg/kg/d) and amiodarone (A; n=20; 50mg/kg/d). Hearts were perfused on a Langendorff apparatus. Results were compared with hearts acutely treated with sotalol (S; 50-100μM; n=14). A 12-lead ECG and up to eight ventricular epi- and endocardial monophasic action potentials (MAP) showed a significant prolongation of QT interval (D: +24ms, A: +28ms, S: +35ms (50μM), +56ms (100μM); p<0.02) as compared with baseline. In contrast to D and A, S led to a significant increase in dispersion of repolarization and exhibited reverse-use dependence. D, A and S increased refractory period, resulting in a significant increase in post-repolarization refractoriness (effective refractory period minus action potential duration; D=+12ms, A=+14ms, S=+25ms; p<0.05). S led to a triangular action potential configuration whereas D and A caused a fast phase-III prolongation. After lowering of potassium concentration, 50% of S-treated hearts showed torsade de pointes (TdP), in contrast to an absence of TdP in D and A. CONCLUSION: Prolongation of myocardial repolarization and post-repolarization refractoriness by D may act antiarrhythmic. A fast phase-3 repolarization in the absence of both - increased dispersion of repolarization and reverse-use dependence - prevents proarrhythmia.
Authors:
Peter Milberg; Gerrit Frommeyer; Timo Uphaus; Dennis Kaiser; Nani Osada; Breithardt Günter; Lars Eckardt
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-9-29
Journal Detail:
Title:  Journal of cardiovascular pharmacology     Volume:  -     ISSN:  1533-4023     ISO Abbreviation:  -     Publication Date:  2011 Sep 
Date Detail:
Created Date:  2011-10-3     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7902492     Medline TA:  J Cardiovasc Pharmacol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
1= Department of Cardiology and Angiology, Division of Clinical and Experimental Electrophysiology, Hospital of the Westfälische Wilhelms-University, Münster, Germany 2 = Department of Medical Informatics and Biomathematics, University of Münster, Germany.
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