Document Detail


Protective activity of the spin trap tert-butyl-alpha-phenyl nitrone (PBN) in reperfused rat heart.
MedLine Citation:
PMID:  1619668     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The aim of this work was to ascertain whether free radicals play a causal role in the injury occurring in myocardial ischemia and reperfusion. To this purpose we observed whether spin-trapping compounds protect the heart when used at a concentration capable of reacting with free radicals. The lipophilic spin trap alpha-phenyl-t-butyl nitrone (PBN) was used because it is taken up by the myocites. Isolated Langendorff rat hearts were subjected to ischemia according to two schemes: "Model A" = 30 min zero-flow ischemia followed by 30 min reperfusion; "Model B" = 60 min of low-flow ischemia (10% of the individual value; N2 saturated) followed by 30 min reperfusion. Treated groups received in addition 5.0 mM PBN which was supplied continuously. The following parameters were measured throughout the experiment: contractile performance (RPP); coronary flow (CF); CPK; phosphocreatine (PCr), ATP, inorganic phosphate (Pi), intracellular pH (pHi). The pathology obtained by "Model A" is more severe than that of Model B, and partly irreversible. During the ischemic phase in "Model A", contractility, PCr and ATP dropped to near zero; during initial reflow CPK rose about 13-fold and Pi rose 2.5-fold, while pHi decreased to 6.1. During reperfusion, a partial recovery of PCr, Pi and pHi was observed, while RPP and ATP did not increase; PBN treatment improved significantly PCr and CPK, while the other parameters were unaffected. During ischemia, "Model B" hearts showed a drop of contractility to near zero, of PCr to 35%, of ATP to 50%; CPK rose 7-fold and Pi 1.5-fold; pHi was not modified. During reperfusion, all parameters recovered in part, with exception of Pi. PBN developed a marked protective activity on all tested parameters, which gained a nearly normal value. The results of the present investigations show that the lipophilic spin trap PBN partly protects the heart from the ischemia/reperfusion injury, thus confirming that free radicals play a causal role in this pathology; the continuous loading of the tissue with the drug can be an important factor for obtaining the protective effect.
Authors:
S Bradamante; E Monti; L Paracchini; E Lazzarini; F Piccinini
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Publication Detail:
Type:  In Vitro; Journal Article    
Journal Detail:
Title:  Journal of molecular and cellular cardiology     Volume:  24     ISSN:  0022-2828     ISO Abbreviation:  J. Mol. Cell. Cardiol.     Publication Date:  1992 Apr 
Date Detail:
Created Date:  1992-08-06     Completed Date:  1992-08-06     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  0262322     Medline TA:  J Mol Cell Cardiol     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  375-86     Citation Subset:  IM    
Affiliation:
CNR-Centro Sintesi e Stereochimica Speciali Sistemi Organici, Università di Milano, Italy.
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MeSH Terms
Descriptor/Qualifier:
Adenosine Triphosphate / metabolism
Animals
Creatine Kinase / metabolism
Cyclic N-Oxides
Hydrogen-Ion Concentration
Male
Myocardial Reperfusion Injury / prevention & control*
Myocardium / metabolism
Nitrogen Oxides / pharmacology*
Phosphates / metabolism
Phosphocreatine / drug effects,  metabolism
Rats
Rats, Inbred Strains
Spin Labels*
Chemical
Reg. No./Substance:
0/Cyclic N-Oxides; 0/Nitrogen Oxides; 0/Phosphates; 0/Spin Labels; 3376-24-7/phenyl-N-tert-butylnitrone; 56-65-5/Adenosine Triphosphate; 67-07-2/Phosphocreatine; EC 2.7.3.2/Creatine Kinase

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


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