Document Detail


8-epi PGF2 alpha generation during coronary reperfusion. A potential quantitative marker of oxidant stress in vivo.
MedLine Citation:
PMID:  9184579     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Myocardial reperfusion is believed to be associated with free radical injury. However, indexes of oxidative stress in vivo have been limited by their poor specificity and sensitivity. Isoprostanes are stable products of arachidonic acid formed in a nonenzymatic, free radical-catalyzed manner. We have developed a sensitive and specific assay for one of these compounds, 8-epi prostaglandin (PG) F2 alpha. METHODS AND RESULTS: To address its utility as an index of oxidative stress during coronary reperfusion, we measured urinary levels by gas chromatography/mass spectrometry in a canine model of coronary thrombolysis, in patients with acute myocardial infarction treated with thrombolytic therapy, and in patients after elective coronary artery bypass surgery. Urinary 8-epi PGF2 alpha was unchanged after circumflex artery occlusion in a canine model of coronary thrombolysis (n = 13; 437.2 +/- 56.4 versus 432.7 +/- 55.2 pmol/mmol creatinine) but increased significantly (P < .05) immediately after reperfusion (553.8 +/- 64.7 pmol/mmol). Urinary levels were increased (P < .001) in patients (n = 12) with acute myocardial infarction given lytic therapy (265.8 +/- 40.8 pmol/mmol) compared with age-matched control subjects (n = 20; 91.5 +/- 11.8 pmol/mmol) and patients with stable coronary disease (n = 20; 95.7 +/- 6.3 pmol/mmol). Preoperative levels rose from 113.2 +/- 11.8 to 248.2 +/- 86.3 pmol/mmol at 30 minutes into revascularization to 332.2 +/- 82.6 pmol/mmol by 15 minutes after global myocardial reperfusion (P < .05) and dropped to 181.2 +/- 50.4 pmol/mmol at 30 minutes and 120.2 +/- 9.9 pmol/mmol at 24 hours after bypass surgery (n = 5). Corresponding changes in spin adduct formation, found with electron paramagnetic resonance, were noted in 2 patients. CONCLUSIONS: These data support the hypothesis that free radical generation occurs during myocardial reperfusion. Measurement of isoprostane production may serve as a noninvasive index of oxidative stress.
Authors:
N Delanty; M P Reilly; D Pratico; J A Lawson; J F McCarthy; A E Wood; S T Ohnishi; D J Fitzgerald; G A FitzGerald
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Circulation     Volume:  95     ISSN:  0009-7322     ISO Abbreviation:  Circulation     Publication Date:  1997 Jun 
Date Detail:
Created Date:  1997-06-27     Completed Date:  1997-06-27     Revised Date:  2009-09-29    
Medline Journal Info:
Nlm Unique ID:  0147763     Medline TA:  Circulation     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  2492-9     Citation Subset:  AIM; IM    
Affiliation:
Center for Experimental Therapeutics, University of Pennsylvania, Philadelphia 19104, USA.
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MeSH Terms
Descriptor/Qualifier:
Adult
Aged
Aged, 80 and over
Animals
Biological Markers / urine*
Coronary Artery Bypass
Dinoprost / analogs & derivatives*,  urine*
Dogs
Electron Spin Resonance Spectroscopy
Female
Gas Chromatography-Mass Spectrometry
Humans
Lipoproteins, LDL / metabolism
Male
Middle Aged
Myocardial Infarction / urine
Myocardial Reperfusion*
Oxidative Stress / physiology*
Sensitivity and Specificity
Thrombolytic Therapy
Grant Support
ID/Acronym/Agency:
HL-54500/HL/NHLBI NIH HHS; MO 1RR00040/RR/NCRR NIH HHS; //Wellcome Trust
Chemical
Reg. No./Substance:
0/Biological Markers; 0/Lipoproteins, LDL; 551-11-1/Dinoprost

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