Document Detail


Exogenous GSH protection during hypoxia-reoxygenation of the isolated rat heart: impact of hypoxia duration.
MedLine Citation:
PMID:  10625216     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The objective of this study was to determine the interaction between duration of myocardial hypoxia and presence of exogenous glutathione (GSH) on functional recovery upon subsequent reoxygenation. Isolated perfused rat hearts were subjected to 20, 30, 40, or 50 min hypoxia (HYP), which resulted in a progressive decline in the amount of contractile recovery (% of normoxic rate-pressure product (RPP) and developed pressure) during 30 min reoxygenation. Supplementation with 5 mM GSH throughout normoxia, hypoxia, and reoxygenation significantly improved contractile recovery during reoxygenation after 20 and 30 min hypoxia (p < 0.05), but had no effect after longer durations of hypoxia when contractile recovery was typically below 40% of RPP and significant areas of no-reflow were observed. ECG analysis revealed that GSH shifted the bell-shaped curve for reperfusion ventricular fibrillation to the right resulting in attenuated fibrillation after 20 and 30 min hypoxia then increased incidences after 40 min when Control hearts were slow to resume electrical activity. ECG conduction velocity was well preserved in all hearts after 20 and 30 min hypoxia, but GSH administration significantly attenuated the decline that occurred with longer durations. GSH supplementation did not attenuate the 35% decline in intracellular thiols during 30 min of hypoxia. When 5 mM GSH was added only during 40 min of hypoxia, RPP recovery after reoxygenation was improved compared to unsupplemented Controls (73% vs. 55% of pre-hypoxia value, p < 0.05). Administration of GSH only during reoxygenation following 40 min of hypoxia did not alter RPP recovery compared to Control hearts. We conclude that cardioprotection by exogenous GSH is dependent on the duration of hypoxia and the functional parameter being evaluated. It is not due to an enhancement of intracellular GSH suggesting that exogenous GSH acts extracellularly to protect sarcolemmal proteins against thiol oxidation during the phase of hypoxia when oxidative stress is a major contributor to cardiac dysfunction. Furthermore, if enough damage accrues during oxygen deprivation, supplementing with GSH during reoxygenation will not impact recovery.
Authors:
K S Seiler; J W Starnes
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Free radical research     Volume:  32     ISSN:  1071-5762     ISO Abbreviation:  Free Radic. Res.     Publication Date:  2000 Jan 
Date Detail:
Created Date:  2000-02-18     Completed Date:  2000-02-18     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  9423872     Medline TA:  Free Radic Res     Country:  SWITZERLAND    
Other Details:
Languages:  eng     Pagination:  41-55     Citation Subset:  IM    
Affiliation:
Department of Kinesiology and Health, The University of Texas at Austin, 78712, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Anoxia / drug therapy*,  metabolism
Coronary Circulation
Electric Conductivity
Electrocardiography
Glutathione / metabolism,  pharmacology*
Heart / drug effects
Male
Myocardial Contraction / drug effects
Myocardium / metabolism*
Rats
Rats, Sprague-Dawley
Reference Values
Sulfhydryl Compounds / metabolism
Time Factors
Ventricular Function
Grant Support
ID/Acronym/Agency:
HL-51005/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Sulfhydryl Compounds; 70-18-8/Glutathione

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


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