Document Detail


Downregulation of immunodetectable connexin43 and decreased gap junction size in the pathogenesis of chronic hibernation in the human left ventricle.
MedLine Citation:
PMID:  9495300     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: The regional wall motion impairment and predisposition to arrhythmias in human ventricular hibernation may plausibly result from abnormal intercellular propagation of the depolarizing wave front. This study investigated the hypothesis that altered patterns of expression of connexin43, the principal gap junctional protein responsible for passive conduction of the cardiac action potential, contribute to the pathogenesis of hibernation. METHODS AND RESULTS: Patients with poor ventricular function and severe coronary artery disease underwent thallium scanning and MRI to predict regions of normally perfused, reversibly ischemic, or hibernating myocardium. Twenty-one patients went on to coronary artery bypass graft surgery, during which biopsies representative of each of the above classes were taken. Hibernation was confirmed by improvement in segmental wall motion at reassessment 6 months after surgery. Connexin43 was studied by quantitative immunoconfocal laser scanning microscopy and PC image software. Analysis of en face projection views of intercalated disks revealed a significant reduction in relative connexin43 content per unit area in reversibly ischemic (76.7+/-34.6%, P<.001) and hibernating (67.4+/-24.3%, P<.001) tissue compared with normal (100+/-30.3%); ANOVA P<.001. The hibernating regions were further characterized by loss of the larger gap junctions normally seen at the disk periphery, reflected by a significant reduction in mean junctional plaque size in the hibernating tissues (69.5+/-20.8%) compared with reversibly ischemic (87.4+/-31.2%, P=.012) and normal (100+/-31.5%, P<.001) segments; ANOVA P<.001. CONCLUSIONS: These results indicate progressive reduction and disruption of connexin43 gap junctions in reversible ischemia and hibernation. Abnormal impulse propagation resulting from such changes may contribute to the electromechanical dysfunction associated with hibernation.
Authors:
R R Kaprielian; M Gunning; E Dupont; M N Sheppard; S M Rothery; R Underwood; D J Pennell; K Fox; J Pepper; P A Poole-Wilson; N J Severs
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Circulation     Volume:  97     ISSN:  0009-7322     ISO Abbreviation:  Circulation     Publication Date:  1998 Feb 
Date Detail:
Created Date:  1998-03-17     Completed Date:  1998-03-17     Revised Date:  2009-09-29    
Medline Journal Info:
Nlm Unique ID:  0147763     Medline TA:  Circulation     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  651-60     Citation Subset:  AIM; IM    
Affiliation:
Cardiac Medicine, Imperial College School of Medicine at the National Heart and Lung Institute, London, England.
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MeSH Terms
Descriptor/Qualifier:
Adult
Aged
Cell Communication*
Connexin 43 / analysis,  biosynthesis*,  genetics
Coronary Disease / complications*,  physiopathology,  surgery
Female
Follow-Up Studies
Gap Junctions / physiology*
Gene Expression Regulation*
Heart Ventricles
Humans
Image Processing, Computer-Assisted
Male
Microscopy, Confocal
Microscopy, Fluorescence
Microscopy, Immunoelectron
Middle Aged
Myocardial Infarction / complications
Myocardial Stunning / etiology*,  genetics,  physiopathology
Ventricular Function, Left
Grant Support
ID/Acronym/Agency:
//Wellcome Trust
Chemical
Reg. No./Substance:
0/Connexin 43
Comments/Corrections
Comment In:
Circulation. 1998 Feb 24;97(7):630-2   [PMID:  9495295 ]

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


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