Document Detail


Postconditioning inhibits mitochondrial permeability transition.
MedLine Citation:
PMID:  15642769     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Brief periods of ischemia performed just at the time of reperfusion can reduce infarct size, a phenomenon called "postconditioning." After reflow, opening of the mitochondrial permeability transition pore (mPTP) has been involved in lethal reperfusion injury. We hypothesized that postconditioning may modulate mPTP opening. METHODS AND RESULTS: Anesthetized open-chest rabbits underwent 30 minutes of ischemia and 4 hours of reperfusion. Control hearts underwent no additional intervention. Postconditioning consisted of 4 episodes of 1 minute of coronary occlusion and 1 minute of reperfusion performed after 1 minute of reflow after the prolonged ischemia. Preconditioning consisted of 5 minutes of ischemia and 5 minutes of reperfusion before the 30-minute ischemia. An additional group of rabbits received 5 mg/kg IV of NIM811, a specific inhibitor of the mPTP, 1 minute before reperfusion. Infarct size was assessed by triphenyltetrazolium staining. Mitochondria were isolated from the risk region myocardium, and Ca2+-induced mPTP opening was assessed by use of a potentiometric method. Postconditioning, preconditioning, and NIM811 significantly limited infarct size, which averaged 29+/-4%, 18+/-4%, and 20+/-4% of the risk region, respectively, versus 61+/-6% in controls (P< or =0.001 versus control). The Ca2+ load required to open the mPTP averaged 41+/-4, 47+/-5, and 67+/-9 micromol/L CaCl2 per mg of mitochondrial proteins in postconditioning, preconditioning, and NIM811, respectively, significantly higher than the value of 16+/-4 micromol/L per mg in controls (P< or =0.05). CONCLUSIONS: Postconditioning inhibits opening of the mPTP and provides a powerful antiischemic protection.
Authors:
Laurent Argaud; Odile Gateau-Roesch; Olivier Raisky; Joseph Loufouat; Dominique Robert; Michel Ovize
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't     Date:  2005-01-10
Journal Detail:
Title:  Circulation     Volume:  111     ISSN:  1524-4539     ISO Abbreviation:  Circulation     Publication Date:  2005 Jan 
Date Detail:
Created Date:  2005-01-19     Completed Date:  2005-07-12     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  0147763     Medline TA:  Circulation     Country:  United States    
Other Details:
Languages:  eng     Pagination:  194-7     Citation Subset:  AIM; IM    
Affiliation:
INSERM E 0226, Université Claude Bernard Lyon I, France.
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MeSH Terms
Descriptor/Qualifier:
Animals
Apoptosis / drug effects,  physiology
Calcium / metabolism*
Coronary Disease / physiopathology*
Cyclosporine / therapeutic use*
Extracellular Signal-Regulated MAP Kinases / physiology
Ion Channel Gating / drug effects,  physiology*
Ion Channels / drug effects,  physiology*
Ion Transport / drug effects,  physiology
MAP Kinase Signaling System / drug effects,  physiology
Male
Membrane Potentials
Mitochondria, Heart / drug effects,  physiology*
Mitochondrial Membrane Transport Proteins
Myocardial Infarction / etiology,  pathology
Myocardial Ischemia / complications,  drug therapy,  therapy*
Myocardial Reperfusion Injury / enzymology,  physiopathology,  prevention & control*
Necrosis
Oxidative Stress
Protein-Serine-Threonine Kinases / physiology
Proto-Oncogene Proteins / physiology
Proto-Oncogene Proteins c-akt
Rabbits
Random Allocation
Time Factors
Chemical
Reg. No./Substance:
0/Ion Channels; 0/Mitochondrial Membrane Transport Proteins; 0/Proto-Oncogene Proteins; 0/mitochondrial permeability transition pore; 143205-42-9/(melle-4)cyclosporin; 59865-13-3/Cyclosporine; 7440-70-2/Calcium; EC 2.7.11.1/Protein-Serine-Threonine Kinases; EC 2.7.11.1/Proto-Oncogene Proteins c-akt; EC 2.7.11.24/Extracellular Signal-Regulated MAP Kinases
Comments/Corrections
Comment In:
Circulation. 2005 Jun 21;111(24):e442; author reply e442   [PMID:  15967857 ]
Circulation. 2005 Jan 18;111(2):120-1   [PMID:  15657384 ]

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