Document Detail

Hemodynamic and metabolic effects of the beta-phosphorylated nitroxide 2-diethoxyphosphoryl-2,5,5-trimethylpyrrolidinoxyl during myocardial ischemia and reperfusion.
MedLine Citation:
PMID:  12706497     Owner:  NLM     Status:  MEDLINE    
In vitro, the stable six-membered ring nitroxide 2,2,6,6-tetramethyl-1-piperidine-N-oxyl (TEMPO) is known to protect the ischemic and reperfused myocardium through a mechanism likely to involve the limitation of free radical damage. In vivo, TEMPO's high rate of reduction into diamagnetic nonactive compounds could limit its pharmacological use and its potential as an ESR probe in oxymetry studies. Recently, beta-phosphorylated nitrones and pyrrolidines have been reported to protect against myocardial reperfusion injury better than their nonphosphorylated analogs. Using hemodynamic, metabolic, and enzymatic indices of reperfusion injury, the efficacy of 2-diethoxyphosphoryl-2,5,5-trimethylpyrrolidinoxyl (TMPPO), a five-membered ring beta-phosphorylated nitroxide, has been compared to that of TEMPO when added at a nontoxic concentration (1 mM) in buffer-perfused isolated rat hearts during low-flow ischemia, total ischemia, and reflow. TMPPO, which is five times as hydrophilic and eight times as resistant to reduction in a biological medium as TEMPO, was more effective in reducing postischemic contracture and myocardial enzymatic leakage. Since a diamagnetic analog of TMPPO was far less protective and both nitroxides showed an antilipoperoxidant effect and acted mainly when administered only at reflow, it was proposed that beta-phosphorylated nitroxides such as TMPPO could be interesting alternatives in pharmacological and ESR applications.
Sylvia Pietri; Anne Mercier; Corinne Mathieu; Sophie Caffaratti; Marcel Culcasi
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Free radical biology & medicine     Volume:  34     ISSN:  0891-5849     ISO Abbreviation:  Free Radic. Biol. Med.     Publication Date:  2003 May 
Date Detail:
Created Date:  2003-04-22     Completed Date:  2004-07-28     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  8709159     Medline TA:  Free Radic Biol Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1167-77     Citation Subset:  IM    
Laboratoire Structure et Réactivité des Espèces Paramagnétiques UMR 6517 du Centre National de la Recherche Scientifique, Universités d'Aix-Marseille I et III, France.
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MeSH Terms
Cardiotonic Agents / pharmacology
Creatine Kinase / metabolism
Cyclic N-Oxides / chemistry,  pharmacology*
Cyclopentanes / chemistry,  pharmacology
Electron Spin Resonance Spectroscopy
Heart / drug effects
Hemodynamics / drug effects*
L-Lactate Dehydrogenase / metabolism
Malondialdehyde / metabolism
Myocardial Ischemia / metabolism*
Myocardial Reperfusion
Myocardial Reperfusion Injury / metabolism*
Myocardium / metabolism*,  pathology
Rats, Wistar
Reg. No./Substance:
0/2-diethoxyphosphoryl-2,5,5-trimethylpyrrolidinoxyl; 0/Cardiotonic Agents; 0/Cyclic N-Oxides; 0/Cyclopentanes; 0/diethyl cyclopentylphosphonate; 2564-83-2/TEMPO; 542-78-9/Malondialdehyde; EC Dehydrogenase; EC Kinase

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