Document Detail


Inhibitory effect of a hydrophilic alpha-tocopherol analogue, MDL 74,405, on generation of free radicals in stunned myocardium in dogs.
MedLine Citation:
PMID:  7633559     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
A previous study has demonstrated that the hydrophilic (alpha-tocopherol analogue, MDL 74,405, attenuates postischemic myocardial dysfunction ("stunning") in dogs. The present study was undertaken to determine directly whether the salutary effect of this drug on myocardial stunning results from inhibition of the generation of oxygen-derived free radicals. Open-chest dogs undergoing a 15-min coronary artery occlusion and 3 h of reperfusion received an intravenous infusion of either saline (controls, n = 7) or MDL 74,405 (n = 6) starting 30 min before coronary occlusion and ending 60 min after reflow at a dose of 0.3 mg/kg/h. To measure free radical production, all dogs received an intravenous infusion of the spin trap alpha-phenyl N-tert-butyl nitrone (PBN) and local coronary venous plasma was analyzed by electron paramagnetic resonance (EPR). In control dogs, the myocardial production of PBN adducts exhibited an initial burst immediately after the onset of reflow and remained elevated until 10 min after reperfusion. Dogs treated with MDL 74,405 demonstrated a marked decrease in PBN adduct production. This effect of MDL 74,405 could not be attributed to nonspecific factors such as differences in ischemic zone size, collateral flow, arterial pressure, heart rate, coronary flow or other hemodynamic variables. These results demonstrate that the hydrophilic vitamin E analogue, MDL 74,405, inhibits free radical generation after myocardial ischemia-reperfusion in vivo. This finding provides direct evidence that the salutary effects of MDL 74,405 on myocardial stunning are due to attenuation of oxidative stress.
Authors:
X L Tang; P B McCay; J Z Sun; C J Hartley; M Schleman; R Bolli
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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:  Free radical research     Volume:  22     ISSN:  1071-5762     ISO Abbreviation:  Free Radic. Res.     Publication Date:  1995 Apr 
Date Detail:
Created Date:  1995-09-14     Completed Date:  1995-09-14     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  9423872     Medline TA:  Free Radic Res     Country:  SWITZERLAND    
Other Details:
Languages:  eng     Pagination:  293-302     Citation Subset:  IM    
Affiliation:
Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Blood Pressure
Body Temperature
Coronary Circulation
Cyclic N-Oxides
Dogs
Electron Spin Resonance Spectroscopy
Free Radicals / metabolism*
Heart Rate
Myocardial Reperfusion
Myocardial Stunning / metabolism*
Myocardium / metabolism*
Nitrogen Oxides / metabolism
Oxidative Stress
Time Factors
Vitamin E / analogs & derivatives*,  chemistry,  metabolism,  pharmacology
Grant Support
ID/Acronym/Agency:
HL-42267/HL/NHLBI NIH HHS; HL-43151/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Cyclic N-Oxides; 0/Free Radicals; 0/Nitrogen Oxides; 130573-32-9/MDL 73404; 1406-18-4/Vitamin E; 3376-24-7/phenyl-N-tert-butylnitrone

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


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