Document Detail


Postconditioning attenuates myocardial injury by reducing nitro-oxidative stress in vivo in rats and in humans.
MedLine Citation:
PMID:  20919993     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
In the present study, we hypothesized that postcon (postconditioning) confers cardioprotection in vivo by reducing the production of ONOO- (peroxynitrite) and nitro-oxidative stress subsequent to the inhibition of the iNOS (inducible NO synthase). Patients with AMI (acute myocardial infarct) were randomly assigned to undergo percutaneous coronary intervention without (control) or with ischaemic postcon by three episodes of 30-s inflation and 30-s deflation of the angioplasty balloon. Animal models of MI/R (myocardial ischaemia/reperfusion) injury were induced in rats by occluding the left coronary artery for 40 min followed by 4-h reperfusion. Rats were randomized to receive vehicle, postcon (three cycles of 10-s reperfusion and 10-s coronary re-occlusion preceding full reperfusion), the selective iNOS inhibitor 1400W or postcon plus 3-morpholinosydnonimine (an ONOO- donor). Postcon in patients reduced iNOS activity in white blood cells, decreased plasma nitrotyrosine, a fingerprint of ONOO- and an index of nitro-oxidative stress, and improved cardiac function (P<0.01 compared with control). In rats, postcon reduced post-ischaemic myocardial iNOS activity and nitrotyrosine formation, reduced myocardial infarct size (all P<0.05 compared with control) and improved cardiac function. Administration of 1400W resembled, whereas 3-morpholinosydnonimine abolished, the effects of postcon. In conclusion, reduction in ONOO--induced nitro-oxidative stress subsequent to the inhibition of iNOS represents a major mechanism whereby postcon confers cardioprotection in vivo.
Authors:
Qian Fan; Xin-Chun Yang; Yu Liu; Le-Feng Wang; Sheng-Hui Liu; Yong-Gui Ge; Mu-Lie Chen; Wen Wang; Li-Ke Zhang; Michael G Irwin; Zhengyuan Xia
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Publication Detail:
Type:  Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Clinical science (London, England : 1979)     Volume:  120     ISSN:  1470-8736     ISO Abbreviation:  Clin. Sci.     Publication Date:  2011 Mar 
Date Detail:
Created Date:  2010-12-03     Completed Date:  2011-02-24     Revised Date:  2011-05-25    
Medline Journal Info:
Nlm Unique ID:  7905731     Medline TA:  Clin Sci (Lond)     Country:  England    
Other Details:
Languages:  eng     Pagination:  251-61     Citation Subset:  IM    
Affiliation:
Beijing Chaoyang Hospital-Affiliate of Beijing Capital Medical University, Beijing, People's Republic of China.
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MeSH Terms
Descriptor/Qualifier:
Aged
Angioplasty, Balloon, Coronary / methods
Animals
Apoptosis
Disease Models, Animal
Dose-Response Relationship, Drug
Enzyme Inhibitors / therapeutic use
Female
Humans
Ischemic Postconditioning / methods*
Leukocyte Count
Male
Malondialdehyde / blood
Middle Aged
Molsidomine / analogs & derivatives,  therapeutic use
Myocardial Infarction / metabolism,  pathology,  therapy
Myocardial Reperfusion Injury / physiopathology,  prevention & control*
Nitric Oxide Synthase Type II / antagonists & inhibitors,  blood
Oxidative Stress / physiology
Rats
Rats, Sprague-Dawley
Treatment Outcome
Tyrosine / analogs & derivatives,  blood
Ventricular Function, Left / physiology
Chemical
Reg. No./Substance:
0/Enzyme Inhibitors; 25717-80-0/Molsidomine; 33876-97-0/3-morpholino-sydnonimine; 3604-79-3/3-nitrotyrosine; 542-78-9/Malondialdehyde; 55520-40-6/Tyrosine; EC 1.14.13.39/Nitric Oxide Synthase Type II

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


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