Document Detail


Electrophysiological consequences of acute regional ischemia/reperfusion in neonatal rat ventricular myocyte monolayers.
MedLine Citation:
PMID:  19015404     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Electrophysiological changes promoting arrhythmias during acute regional ischemia/reperfusion are challenging to study in intact cardiac tissue because of complex 3-dimensional myocardial and vascular geometry. We characterized electrophysiological alterations and arrhythmias during regional ischemia/reperfusion in a simpler 2-dimensional geometry of cultured neonatal rat ventricular myocyte monolayers.
METHODS AND RESULTS: Optical mapping of intracellular Ca (Ca(i)) and voltage was performed with the use of Rhod 2-AM and Rh-237, respectively. Regional ischemia was mimicked by covering the central portion of monolayer with a glass coverslip, and reperfusion was mimicked by removing the coverslip. Monolayers were stained with fluorescent antibodies to detect total and dephosphorylated connexin-43 at various time points. During coverslip ischemia, action potential duration shortened, Ca(i) transient duration was prolonged, and local conduction velocity (CV) slowed progressively, with loss of excitability after 10.6 +/- 3.6 minutes. CV slowing was accompanied by connexin-43 dephosphorylation. During ischemia, spontaneous reentry occurred in 5 of 11 monolayers, initiated by extrasystoles arising from the border zone or unidirectional conduction block of paced beats. On reperfusion, excitability recovered within 1.0 +/- 0.8 minutes, but CV remained depressed for 9.0 +/- 3.0 minutes, promoting reentry in the reperfused zone. As connexin-43 phosphorylation recovered in the reperfused zone, CV normalized, and arrhythmias resolved.
CONCLUSIONS: Acute regional ischemia/reperfusion in neonatal rat ventricular myocyte monolayers recapitulates electrophysiological alterations and arrhythmias similar to those observed during acute coronary occlusion/reperfusion in intact hearts. During early reperfusion, slow recovery from connexin-43 dephosphorylation leads to persistent CV slowing, creating a highly arrhythmogenic substrate.
Authors:
Carlos de Diego; Rakesh K Pai; Fuhua Chen; Lai-Hua Xie; Jan De Leeuw; James N Weiss; Miguel Valderrábano
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2008-11-17
Journal Detail:
Title:  Circulation     Volume:  118     ISSN:  1524-4539     ISO Abbreviation:  Circulation     Publication Date:  2008 Dec 
Date Detail:
Created Date:  2008-12-02     Completed Date:  2008-12-17     Revised Date:  2013-06-04    
Medline Journal Info:
Nlm Unique ID:  0147763     Medline TA:  Circulation     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2330-7     Citation Subset:  AIM; IM    
Affiliation:
UCLA Cardiovascular Research Laboratory, Department of Medicine, Division of Cardiology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Animals, Newborn
Arrhythmias, Cardiac
Connexin 43 / metabolism
Electrophysiology*
Heart Ventricles / pathology*
Models, Cardiovascular
Muscle Cells / pathology*
Myocardial Reperfusion Injury / physiopathology*
Phosphorylation
Rats
Grant Support
ID/Acronym/Agency:
P01 HL078931/HL/NHLBI NIH HHS; P01 HL078931-01A1/HL/NHLBI NIH HHS; P01 HL078931-02/HL/NHLBI NIH HHS; P01 HL078931-02S1/HL/NHLBI NIH HHS; P01 HL078931-03/HL/NHLBI NIH HHS; P01 HL078931-04/HL/NHLBI NIH HHS; P01 HL078931-05/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Connexin 43
Comments/Corrections

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