| Heterogeneous Connexin43 distribution in heart failure is associated with dispersed conduction and enhanced susceptibility to ventricular arrhythmias. | |
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MedLine Citation:
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PMID: 20534605 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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AIMS: Sudden arrhythmogenic cardiac death is a major cause of mortality in patients with congestive heart failure (CHF). To investigate determinants of the increased arrhythmogenic susceptibility, we studied cardiac remodelling and arrhythmogenicity in CHF patients and in a mouse model of chronic pressure overload. METHODS AND RESULTS: Clinical and (immuno)histological data of myocardial biopsies from CHF patients with (VT+) and without (VT-) documented ventricular arrhythmia were compared with controls. In CHF patients, ejection fraction was decreased and QRS duration was increased. Cell size and interstitial fibrosis were increased, but Connexin43 (Cx43) levels, the most abundant gap junction in ventricular myocardium, were unchanged. No differences were found between VT+ and VT- patients, except for the distribution pattern of Cx43, which was significantly more heterogeneous in VT+. Mice were subjected to transverse aortic constriction (TAC) or sham operated. At 16 weeks, cardiac function was determined by echocardiography and epicardial ventricular activation mapping was performed. Transverse aortic constriction mice had decreased fractional shortening and prolonged QRS duration. Right ventricular conduction velocity was reduced, and polymorphic VTs were induced in 44% TAC and 0% sham mice. Interstitial fibrosis was increased and Cx43 quantity was unchanged in TAC mice with and without arrhythmias. Similar to CHF patients, heterogeneous Cx43 distribution was significantly associated with arrhythmias in TAC mice and with spatial heterogeneity of impulse conduction. CONCLUSION: Heterogeneous Cx43 expression during CHF is associated with dispersed impulse conduction and may underlie enhanced susceptibility to ventricular tachyarrhythmias. |
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Authors:
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Mohamed Boulaksil; Stephan K G Winckels; Markus A Engelen; Mèra Stein; Toon A B van Veen; John A Jansen; André C Linnenbank; Marti F A Bierhuizen; W Antoinette Groenewegen; Matthijs F M van Oosterhout; Johannes H Kirkels; Nicolaas de Jonge; András Varró; Marc A Vos; Jacques M T de Bakker; Harold V M van Rijen |
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Publication Detail:
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Type: Comparative Study; Journal Article; Research Support, Non-U.S. Gov't Date: 2010-06-09 |
Journal Detail:
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Title: European journal of heart failure Volume: 12 ISSN: 1879-0844 ISO Abbreviation: Eur. J. Heart Fail. Publication Date: 2010 Sep |
Date Detail:
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Created Date: 2010-08-23 Completed Date: 2011-01-11 Revised Date: 2011-06-08 |
Medline Journal Info:
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Nlm Unique ID: 100887595 Medline TA: Eur J Heart Fail Country: Netherlands |
Other Details:
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Languages: eng Pagination: 913-21 Citation Subset: IM |
Affiliation:
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Interuniversity Cardiology Institute of The Netherlands, Utrecht, The Netherlands. |
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Biopsy Connexin 43 / metabolism* Disease Models, Animal Disease Progression Echocardiography Electrocardiography Female Heart Failure / diagnosis, metabolism*, physiopathology Humans Immunohistochemistry Male Mice Mice, Inbred C57BL Middle Aged Myocardium / metabolism*, pathology Tachycardia, Ventricular / diagnosis, metabolism*, physiopathology |
| Chemical | |
Reg. No./Substance:
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0/Connexin 43 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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