Document Detail

Repetitive ischemia by coronary stenosis induces a novel window of ischemic preconditioning.
MedLine Citation:
PMID:  18936329     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: The hypothesis of the present study was that molecular mechanisms differ markedly when mediating ischemic preconditioning induced by repetitive episodes of ischemia versus classic first- or second-window preconditioning.
METHODS AND RESULTS: To test this, chronically instrumented conscious pigs were subjected to either repetitive coronary stenosis (RCS) or a traditional protocol of second-window ischemic preconditioning (SWIPC). Lethal ischemia, induced by 60 minutes of coronary artery occlusion followed by reperfusion, resulted in an infarct size/area at risk of 6+/-3% after RCS and 16+/-3% after SWIPC (both groups P<0.05, less than shams 42+/-4%). Two molecular signatures of SWIPC, the increased expression of the inducible isoform of nitric oxide synthase and the translocation of protein kinase Cepsilon to the plasma membrane, were observed with SWIPC but not with RCS. Confirming this, pretreatment with a nitric oxide synthase inhibitor prevented the protection conferred by SWIPC but not by RCS. Microarray analysis revealed a qualitatively different genomic profile of cardioprotection between ischemic preconditioning induced by RCS and that induced by SWIPC. The number of genes significantly regulated was greater in RCS (5739) than in SWIPC (2394) animals. Of the 5739 genes regulated in RCS, only 31% were also regulated in SWIPC. Broad categories of genes induced by RCS but not SWIPC included those involved in autophagy, endoplasmic reticulum stress, and mitochondrial oxidative metabolism. The upregulation of these pathways was confirmed by Western blotting.
CONCLUSIONS: RCS induces cardioprotection against lethal myocardial ischemia that is at least as powerful as traditional ischemic preconditioning but is mediated through radically different mechanisms.
You-Tang Shen; Christophe Depre; Lin Yan; Ji Yeon Park; Bin Tian; Komal Jain; Li Chen; Yan Zhang; Raymond K Kudej; Xin Zhao; Junichi Sadoshima; Dorothy E Vatner; Stephen F Vatner
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2008-10-20
Journal Detail:
Title:  Circulation     Volume:  118     ISSN:  1524-4539     ISO Abbreviation:  Circulation     Publication Date:  2008 Nov 
Date Detail:
Created Date:  2008-11-04     Completed Date:  2008-11-26     Revised Date:  2014-09-24    
Medline Journal Info:
Nlm Unique ID:  0147763     Medline TA:  Circulation     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1961-9     Citation Subset:  AIM; IM    
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MeSH Terms
Coronary Circulation
Coronary Stenosis / metabolism*,  physiopathology*
Disease Models, Animal
Enzyme Inhibitors / pharmacology
Ischemic Preconditioning, Myocardial*
Myocardial Reperfusion Injury / metabolism*,  physiopathology*
Myocardial Stunning / metabolism,  physiopathology
Nitric Oxide / metabolism
Nitric Oxide Synthase Type II / metabolism
Nitroarginine / pharmacology
Oligonucleotide Array Sequence Analysis
Protein Kinase C-epsilon / metabolism
Grant Support
AG014121/AG/NIA NIH HHS; AG023137/AG/NIA NIH HHS; AG023567/AG/NIA NIH HHS; AG027211/AG/NIA NIH HHS; HL033107/HL/NHLBI NIH HHS; HL059139/HL/NHLBI NIH HHS; HL069020/HL/NHLBI NIH HHS; HL069752/HL/NHLBI NIH HHS; P01 AG027211/AG/NIA NIH HHS; P01 AG027211-02/AG/NIA NIH HHS; P01 HL059139/HL/NHLBI NIH HHS; P01 HL059139-10/HL/NHLBI NIH HHS; P01 HL069020/HL/NHLBI NIH HHS; P01 HL069020-08/HL/NHLBI NIH HHS; R01 AG014121/AG/NIA NIH HHS; R01 AG014121-11/AG/NIA NIH HHS; R01 AG023137/AG/NIA NIH HHS; R01 AG023137-05/AG/NIA NIH HHS; R01 AG023567/AG/NIA NIH HHS; R01 AG023567-03/AG/NIA NIH HHS; R01 HL033107/HL/NHLBI NIH HHS; R01 HL033107-24/HL/NHLBI NIH HHS; T32 HL069752/HL/NHLBI NIH HHS; T32 HL069752-05/HL/NHLBI NIH HHS
Reg. No./Substance:
0/Enzyme Inhibitors; 2149-70-4/Nitroarginine; 31C4KY9ESH/Nitric Oxide; EC Oxide Synthase Type II; EC Kinase C-epsilon
Comment In:
Circulation. 2008 Nov 4;118(19):1915-9   [PMID:  18981312 ]

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

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