Document Detail

Changes in connexin expression and the atrial fibrillation substrate in congestive heart failure.
MedLine Citation:
PMID:  19875729     Owner:  NLM     Status:  MEDLINE    
RATIONALE: Although connexin changes are important for the ventricular arrhythmic substrate in congestive heart failure (CHF), connexin alterations during CHF-related atrial arrhythmogenic remodeling have received limited attention. OBJECTIVE: To analyze connexin changes and their potential contribution to the atrial fibrillation (AF) substrate during the development and reversal of CHF. METHODS AND RESULTS: Three groups of dogs were studied: CHF induced by 2-week ventricular tachypacing (240 bpm, n=15); CHF dogs allowed a 4-week nonpaced recovery interval after 2-week tachypacing (n=16); and nonpaced sham controls (n=19). Left ventricular (LV) end-diastolic pressure and atrial refractory periods increased with CHF and normalized on CHF recovery. CHF caused abnormalities in atrial conduction indexes and increased the duration of burst pacing-induced AF (DAF, from 22+/-7 seconds in control to 1100+/-171 seconds, P<0.001). CHF did not significantly alter overall atrial connexin (Cx)40 and Cx43 mRNA and protein expression levels, but produced Cx43 dephosphorylation, increased Cx40/Cx43 protein expression ratio and caused Cx43 redistribution toward transverse cell-boundaries. All of the connexin-alterations reversed on CHF recovery, but CHF-induced conduction abnormalities and increased DAF (884+/-220 seconds, P<0.001 versus control) remained. The atrial fibrous tissue content increased from 3.6+/-0.7% in control to 14.7+/-1.5% and 13.3+/-2.3% in CHF and CHF recovery, respectively (both P<0.01 versus control), with transversely running zones of fibrosis physically separating longitudinally directed muscle bundles. In an ionically based action potential/tissue model, fibrosis was able to account for conduction abnormalities associated with CHF and recovery. CONCLUSIONS: CHF causes atrial connexin changes, but these are not essential for CHF-related conduction disturbances and AF promotion, which are rather related primarily to fibrotic interruption of muscle bundle continuity.
Brett Burstein; Philippe Comtois; Georghia Michael; Kunihiro Nishida; Louis Villeneuve; Yung-Hsin Yeh; Stanley Nattel
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-10-29
Journal Detail:
Title:  Circulation research     Volume:  105     ISSN:  1524-4571     ISO Abbreviation:  Circ. Res.     Publication Date:  2009 Dec 
Date Detail:
Created Date:  2009-12-04     Completed Date:  2009-12-17     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0047103     Medline TA:  Circ Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1213-22     Citation Subset:  IM    
Department of Medicine and Physiology/Institute of Biomedical Engineering, Research Center Montreal Heart Institute and Universit?? de Montr??al, Montreal, Quebec, Canada.
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MeSH Terms
Action Potentials
Atrial Fibrillation / etiology,  metabolism*,  pathology,  physiopathology
Atrial Function
Cardiac Pacing, Artificial
Connexin 43 / genetics,  metabolism*
Connexins / genetics,  metabolism*
Disease Models, Animal
Electrophysiologic Techniques, Cardiac
Heart Failure / complications,  metabolism*,  pathology,  physiopathology
Models, Cardiovascular
Myocardium / metabolism*,  pathology
RNA, Messenger / metabolism
Recovery of Function
Refractory Period, Electrophysiological
Time Factors
Ventricular Function, Left
Ventricular Pressure
Grant Support
MGP 6957//Canadian Institutes of Health Research
Reg. No./Substance:
0/Connexin 43; 0/Connexins; 0/RNA, Messenger; 0/connexin 40

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

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