title: Postconditioning inhibits mitochondrial permeability transition.
abstract: 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.
  
  
  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.affiliation: INSERM E 0226, Université Claude Bernard Lyon I, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Argaud
authors.forename: Odile
authors.initials: O
authors.lastname: Gateau-Roesch
authors.forename: Olivier
authors.initials: O
authors.lastname: Raisky
authors.forename: Joseph
authors.initials: J
authors.lastname: Loufouat
authors.forename: Dominique
authors.initials: D
authors.lastname: Robert
authors.forename: Michel
authors.initials: M
authors.lastname: Ovize
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D002118:Calcium / Q000378:metabolism*; D003327:Coronary Disease / Q000503:physiopathology*; D016572:Cyclosporine / Q000627:therapeutic use*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000502:physiology; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology*; D007473:Ion Channels / Q000187:drug effects / Q000502:physiology*; D017136:Ion Transport / Q000187:drug effects / Q000502:physiology; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology; D008297:Male; D008564:Membrane Potentials; D008929:Mitochondria, Heart / Q000187:drug effects / Q000502:physiology*; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D009203:Myocardial Infarction / Q000209:etiology / Q000473:pathology; D017202:Myocardial Ischemia / Q000150:complications / Q000188:drug therapy / Q000628:therapy*; D015428:Myocardial Reperfusion Injury / Q000201:enzymology / Q000503:physiopathology / Q000517:prevention & control*; D009336:Necrosis; D018384:Oxidative Stress; D017346:Protein Serine-Threonine Kinases / Q000502:physiology; D011518:Proto-Oncogene Proteins / Q000502:physiology; D051057:Proto-Oncogene Proteins c-akt; D011817:Rabbits; D011897:Random Allocation; D013997:Time Factors
chemical_list: D007473:Ion Channels; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D011518:Proto-Oncogene Proteins; D016572:Cyclosporine; C090438:(melle-4)cyclosporin; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D002118:Calcium