Document Detail


Characterization of gap junction remodeling in epicardial border zone of healing canine infarcts and electrophysiological effects of partial reversal by rotigaptide.
MedLine Citation:
PMID:  21493965     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: The border zone of healing myocardial infarcts is an arrhythmogenic substrate, partly the result of structural and functional remodeling of the ventricular gap junction protein, Connexin43 (Cx43). Cx43 in arrhythmogenic substrates is a potential target for antiarrhythmic therapy.
METHODS AND RESULTS: We characterized Cx43 remodeling in the epicardial border zone (EBZ) of healing canine infarcts 5 days after coronary occlusion and examined whether the gap junction-specific agent rotigaptide could reverse it. Cx43 remodeling in the EBZ was characterized by a decrease in Cx43 protein, lateralization, and increased Cx43 phosphorylation at serine (S) 368. Rotigaptide partially reversed the loss of Cx43 but did not affect the increase in S368 phosphorylation, nor did it reverse Cx43 lateralization. Rotigaptide did not prevent conduction slowing in the EBZ, nor did it decrease the induction of sustained ventricular tachycardia by programmed stimulation, although it did decrease the EBZ effective refractory period.
CONCLUSIONS: We conclude that partial reversal of Cx43 remodeling in healing infarct border zone may not be sufficient to restore normal conduction or prevent arrhythmias.
Authors:
Ester Macia; Elena Dolmatova; Candido Cabo; Alexandra Z Sosinsky; Wen Dun; James Coromilas; Edward J Ciaccio; Penelope A Boyden; Andrew L Wit; Heather S Duffy
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-04-14
Journal Detail:
Title:  Circulation. Arrhythmia and electrophysiology     Volume:  4     ISSN:  1941-3084     ISO Abbreviation:  Circ Arrhythm Electrophysiol     Publication Date:  2011 Jun 
Date Detail:
Created Date:  2011-06-15     Completed Date:  2011-09-01     Revised Date:  2013-06-30    
Medline Journal Info:
Nlm Unique ID:  101474365     Medline TA:  Circ Arrhythm Electrophysiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  344-51     Citation Subset:  IM    
Affiliation:
Department of Pharmacology, Center for Molecular Therapeutics, Columbia University, New York, NY, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Disease Models, Animal
Dogs
Electrophysiological Phenomena / drug effects,  physiology*
Gap Junctions / drug effects,  physiology*
Heart Conduction System / drug effects,  metabolism,  physiopathology
Myocardial Infarction / complications*,  metabolism,  physiopathology
Oligopeptides / pharmacology*
Pericardium / metabolism*,  physiopathology
Recovery of Function / physiology*
Tachycardia, Ventricular / drug therapy,  etiology,  metabolism*
Grant Support
ID/Acronym/Agency:
HL066140/HL/NHLBI NIH HHS; HL083205/HL/NHLBI NIH HHS; R01 HL083205-05/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Oligopeptides; GFA1W6KO7N/rotigaptide
Comments/Corrections

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