Gap junction uncoupler heptanol prevents cell-to-cell progression of hypercontracture and limits necrosis during myocardial reperfusion

The objective of this study was to test the hypothesis that chemical interaction through gap junctions may result in cell-to-cell progression of hypercontracture and that this phenomenon contributes to the final extent of reperfused infarcts. Cell-to-cell transmission of hypercontracture was studied...

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Bibliographic Details
Published in:Circulation (New York, N.Y.) N.Y.), 1997-11, Vol.96 (10), p.3579-3586
Main Authors: GARCIA-DORADO, D, INSERTE, J, RUIZ-MEANA, M, GONZALEZ, M. A, SOLARES, J, JULIA, M, BARRABES, J. A, SOLER-SOLER, J
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Cardiology. Vascular system
Cell Separation
Coronary Circulation - drug effects
Coronary Disease - physiopathology
Coronary heart disease
Disease Progression
Gap Junctions - drug effects
Heart
Heart - drug effects
Hemodynamics - drug effects
Heptanol - pharmacology
Hypoxia - physiopathology
In Vitro Techniques
Medical sciences
Myocardial Contraction - drug effects
Myocardial Reperfusion Injury - pathology
Myocardial Reperfusion Injury - physiopathology
Myocardium - pathology
Necrosis
Rats
Rats, Sprague-Dawley
Uncoupling Agents - pharmacology
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Summary:The objective of this study was to test the hypothesis that chemical interaction through gap junctions may result in cell-to-cell progression of hypercontracture and that this phenomenon contributes to the final extent of reperfused infarcts. Cell-to-cell transmission of hypercontracture was studied in pairs of freshly isolated adult rat cardiomyocytes. Hypercontracture induced by microinjection of a solution containing 1 mmol/L Ca2+ and 2% lucifer yellow (LY) was transmitted to the adjacent cell (11 of 11 pairs), and the gap junction uncoupler heptanol (2 mmol/L) prevented transmission in 6 of 8 pairs (P=.003), with a perfect association between passage of the LY and transmission of hypercontracture. In the isolated, perfused rat heart submitted to 30 minutes of hypoxia, addition of heptanol to the perfusion media during the first 15 minutes of reoxygenation had a dose-related protective effect against the oxygen paradox, as demonstrated by a reduction of diastolic pressure and marked recovery of developed pressure (P
ISSN:0009-7322
1524-4539
DOI:10.1161/01.cir.96.10.3579