| Use of spin traps in intact animals undergoing myocardial ischemia/reperfusion: a new approach to assessing the role of oxygen radicals in myocardial "stunning". | |
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MedLine Citation:
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PMID: 2167254 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Numerous studies have indirectly suggested that oxygen-derived free radicals play an important pathogenetic role in the prolonged depression of contractile function observed in myocardium reperfused after reversible ischemia (myocardial "stunning"). In order to provide direct evidence for the oxy-radical hypothesis of stunning, we administered the spin trap, alpha-phenyl N-tert-butyl nitrone (PBN), to open-chest dogs undergoing a 15-min coronary artery occlusion followed by reperfusion. Plasma of local coronary venous blood was analyzed by electron paramagnetic resonance (EPR) spectroscopy. EPR signals characteristic of radical adducts of PBN appeared during ischemia and increased dramatically in the first few minutes after reperfusion. After this initial burst, the production of adducts abated but did not cease, persisting up to 3 h after reflow. The production of PBN adducts after reperfusion was inversely related to collateral flow during ischemia. PBN itself enhanced recovery of contractile function, indicating that the radicals trapped may play a pathogenetic role in myocardial stunning. Superoxide dismutase plus catalase attenuated PBN adduct production and, at the same time, improved recovery of contractile function. Antioxidant therapy given 1 min before reperfusion suppressed PBN adduct production and improved contractile recovery; however, the same therapy given 1 min after reperfusion did not suppress early radical production and did not attenuate contractile dysfunction. After i.v. administration, the elimination half-life of PBN was estimated to be approximately 4-5 h. The results demonstrate that 1) free radicals are produced in the stunned myocardium in intact animals; 2) inhibition of free radical production results in improved contractile recovery; and 3) the free radicals important in causing dysfunction are produced in the first few minutes of reperfusion. Taken together, these studies provide cogent evidence supporting the oxy-radical hypothesis of stunning in open-chest dogs. It is now critical to determine whether these results can be reproduced in conscious animal preparations. |
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Authors:
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R Bolli; P B McCay |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Free radical research communications Volume: 9 ISSN: 8755-0199 ISO Abbreviation: Free Radic. Res. Commun. Publication Date: 1990 |
Date Detail:
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Created Date: 1990-09-25 Completed Date: 1990-09-25 Revised Date: 2007-11-15 |
Medline Journal Info:
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Nlm Unique ID: 8709453 Medline TA: Free Radic Res Commun Country: SWITZERLAND |
Other Details:
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Languages: eng Pagination: 169-80 Citation Subset: IM |
Affiliation:
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Department of Medicine, Baylor College of Medicine, Houston, Texas 77030. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Catalase / pharmacology Cyclic N-Oxides Dogs Electron Spin Resonance Spectroscopy* Free Radicals* Half-Life Myocardial Reperfusion Injury / metabolism* Nitrogen Oxides / diagnostic use Oxygen / metabolism* Spin Labels* Superoxide Dismutase / pharmacology Thiopronine / pharmacology |
| Grant Support | |
ID/Acronym/Agency:
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2507RR05538-25/RR/NCRR NIH HHS; GM36512/GM/NIGMS NIH HHS; HL36277/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Cyclic N-Oxides; 0/Free Radicals; 0/Nitrogen Oxides; 0/Spin Labels; 1953-02-2/Thiopronine; 3376-24-7/phenyl-N-tert-butylnitrone; 7782-44-7/Oxygen; EC 1.11.1.6/Catalase; EC 1.15.1.1/Superoxide Dismutase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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