title: Post-conditioning protects from cardioplegia and cold ischemia via inhibition of mitochondrial permeability transition pore.
abstract: BACKGROUND
  The aim of this study was to evaluate the role of the mitochondrial permeability transition pore (MPTP) in the protection achieved by post-conditioning of hearts submitted to hypothermic cardioplegia and ischemia.
  
  
  METHODS
  Isolated rat hearts (n = 30) underwent cold cardioplegia (4 degrees C, Celsior solution) and 8 hours of ischemia at 4 degrees C, followed by a 60-minute Langendorff reperfusion. Hearts were randomly assigned to one of two groups: post-conditioning (post-C, consisting of episodes of 30-second ischemia and 30-second reperfusion at onset of reperfusion) or control (no intervention). A sham group was added for which hearts were harvested and immediately reperfused without ischemia. Coronary flow, heart rate, dP/dt and rate-pressure product were measured. Infarct size was assessed by triphenyltetrazolium chloride (TTC) staining and lactate dehydrogenase (LDH), creatine phosphokinase (CPK) and troponin I release analysis. After reperfusion, heart mitochondria were isolated and calcium overload necessary to induce MPTP opening was measured. From the onset of reperfusion, all functional parameters were significantly improved in post-C vs control hearts.
  
  
  RESULTS
  Infarct size, measured both by TTC staining and LDH, and CPK and troponin I leakage were lower in post-C hearts (p < 0.01). Mean calcium load needed to induce MPTP opening was higher in post-C mitochondria vs controls (p < 0.01).
  
  
  CONCLUSIONS
  Post-conditioning protects the rat heart against cold ischemia-reperfusion injury. Our data suggest that this protection involves inhibition of MPTP opening.
authors.affiliation: INSERM U 886, Faculté de Médecine Lyon-Nord, Université Claude Bernard Lyon-1, Lyon, France. ferrera@lyon.inserm.fr
authors.forename: René
authors.initials: R
authors.lastname: Ferrera
authors.forename: Jean-Chrisostome
authors.initials: JC
authors.lastname: Bopassa
authors.forename: Denis
authors.initials: D
authors.lastname: Angoulvant
authors.forename: Michel
authors.initials: M
authors.lastname: Ovize
mesh_terms: D000818:Animals; D002118:Calcium / Q000502:physiology; D003080:Cold Temperature; D004195:Disease Models, Animal; D006323:Heart Arrest / Q000517:prevention & control; D006324:Heart Arrest, Induced; D007511:Ischemia / Q000517:prevention & control; D008297:Male; D033681:Mitochondrial Membrane Transport Proteins / Q000187:drug effects / Q000502:physiology*; D000083162:Mitochondrial Permeability Transition Pore; D009203:Myocardial Infarction / Q000503:physiopathology / Q000517:prevention & control*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D019172:Transplantation Conditioning / Q000379:methods*
chemical_list: D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D002118:Calcium