Document Detail


Suppression of re-entrant and multifocal ventricular fibrillation by the late sodium current blocker ranolazine.
MedLine Citation:
PMID:  21232675     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVES: The purpose of this study was to test the hypothesis that the late Na current blocker ranolazine suppresses re-entrant and multifocal ventricular fibrillation (VF).
BACKGROUND: VF can be caused by either re-entrant or focal mechanism.
METHODS: Simultaneous voltage and intracellular Ca(+)² optical mapping of the left ventricular epicardial surface along with microelectrode recordings was performed in 24 isolated-perfused aged rat hearts. Re-entrant VF was induced by rapid pacing and multifocal VF by exposure to oxidative stress with 0.1 mM hydrogen peroxide (H₂O₂).
RESULTS: Rapid pacing induced sustained VF in 7 of 8 aged rat hearts, characterized by 2 to 4 broad propagating wavefronts. Ranolazine significantly (p < 0.05) reduced the maximum slope of action potential duration restitution curve and converted sustained to nonsustained VF lasting 24 ± 8 s in all 7 hearts. Exposure to H₂O₂ initiated early afterdepolarization (EAD)-mediated triggered activity that led to sustained VF in 8 out of 8 aged hearts. VF was characterized by multiple foci, appearing at an average of 6.8 ± 3.2 every 100 ms, which remained confined to a small area averaging 2.8 ± 0.85 mm² and became extinct after a mean of 43 ± 16 ms. Ranolazine prevented (when given before H₂O₂) and suppressed H₂O₂-mediated EADs by reducing the number of foci, causing VF to terminate in 8 out of 8 hearts. Simulations in 2-dimensional tissue with EAD-mediated multifocal VF showed progressive reduction in the number of foci and VF termination by blocking the late Na current.
CONCLUSIONS: Late Na current blockade with ranolazine is effective at suppressing both pacing-induced re-entrant VF and EAD-mediated multifocal VF.
Authors:
Norishige Morita; Jong Hwan Lee; Yuanfang Xie; Ali Sovari; Zhilin Qu; James N Weiss; Hrayr S Karagueuzian
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of the American College of Cardiology     Volume:  57     ISSN:  1558-3597     ISO Abbreviation:  J. Am. Coll. Cardiol.     Publication Date:  2011 Jan 
Date Detail:
Created Date:  2011-01-14     Completed Date:  2011-02-14     Revised Date:  2013-03-21    
Medline Journal Info:
Nlm Unique ID:  8301365     Medline TA:  J Am Coll Cardiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  366-75     Citation Subset:  AIM; IM    
Copyright Information:
Copyright © 2011 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
Affiliation:
Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California 90095, USA.
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MeSH Terms
Descriptor/Qualifier:
Acetanilides / pharmacology,  therapeutic use*
Action Potentials / drug effects*,  physiology*
Animals
Male
Piperazines / pharmacology,  therapeutic use*
Rats
Rats, Inbred F344
Sodium Channel Blockers / pharmacology,  therapeutic use*
Ventricular Fibrillation / drug therapy*,  metabolism,  physiopathology*
Grant Support
ID/Acronym/Agency:
P01 HL078931/HL/NHLBI NIH HHS; P01 HL78931/HL/NHLBI NIH HHS; R01 HL103662/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Acetanilides; 0/Piperazines; 0/Sodium Channel Blockers; 110445-25-5/ranolazine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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