| Changes in connexin expression and the atrial fibrillation substrate in congestive heart failure. | |
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MedLine Citation:
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PMID: 19875729 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Brett Burstein; Philippe Comtois; Georghia Michael; Kunihiro Nishida; Louis Villeneuve; Yung-Hsin Yeh; Stanley Nattel |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2009-10-29 |
Journal Detail:
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Title: Circulation research Volume: 105 ISSN: 1524-4571 ISO Abbreviation: Circ. Res. Publication Date: 2009 Dec |
Date Detail:
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Created Date: 2009-12-04 Completed Date: 2009-12-17 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0047103 Medline TA: Circ Res Country: United States |
Other Details:
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Languages: eng Pagination: 1213-22 Citation Subset: IM |
Affiliation:
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Department of Medicine and Physiology/Institute of Biomedical Engineering, Research Center Montreal Heart Institute and Universit?? de Montr??al, Montreal, Quebec, Canada. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Action Potentials Animals Atrial Fibrillation / etiology, metabolism*, pathology, physiopathology Atrial Function Cardiac Pacing, Artificial Connexin 43 / genetics, metabolism* Connexins / genetics, metabolism* Disease Models, Animal Dogs Electrophysiologic Techniques, Cardiac Fibrosis Heart Failure / complications, metabolism*, pathology, physiopathology Models, Cardiovascular Myocardium / metabolism*, pathology Phosphorylation RNA, Messenger / metabolism Recovery of Function Refractory Period, Electrophysiological Time Factors Ventricular Function, Left Ventricular Pressure |
| Grant Support | |
ID/Acronym/Agency:
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MGP 6957//Canadian Institutes of Health Research |
| Chemical | |
Reg. No./Substance:
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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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