title: Delayed low pressure at reperfusion: A new approach for cardioprotection.
abstract: OBJECTIVE
  The aims of this study were to evaluate whether the delayed application of low-pressure reperfusion could reduce lethal reperfusion injury and whether the inhibition of the opening of the mitochondrial permeability transition pore is involved in this protection.
  
  
  METHODS
  Isolated rat hearts (n = 120) underwent 40 minutes of global ischemia followed by 60 minutes of reperfusion. Hearts were randomly assigned to the following groups: control, postconditioning (comprising 2 episodes of 30 seconds of ischemia and 30 seconds of reperfusion), and low-pressure reperfusion (using a reduction of perfusion pressure at 70 cm H2O for 10 minutes). In additional groups, postconditioning and low-pressure reperfusion were applied after a delay of 3, 10, and 20 minutes after the initial 40-minute ischemic insult.
  
  
  RESULTS
  As expected, infarct size (triphenyltetrazolium chloride staining) and lactate dehydrogenase release were significantly reduced in low-pressure reperfusion and postconditioning versus controls (P < .01), whereas functional parameters (coronary flow, rate pressure product) were improved (P < .01). Although delaying postconditioning by more than 3 minutes resulted in a loss of protection, low-pressure reperfusion still significantly reduced infarct size when applied as late as 20 minutes after reperfusion. This delayed low-pressure reperfusion protection was associated with an improved mitochondrial respiration, lower reactive oxygen species production, and enhanced calcium retention capacity, related to inhibition of permeability transition pore opening.
  
  
  CONCLUSIONS
  We demonstrated for the first time that low-pressure reperfusion can reduce lethal myocardial reperfusion injury even when performed 10 to 20 minutes after the initiation of reperfusion.
authors.affiliation: Université Lyon 1, Lyon, France. Electronic address: rene.ferrera@univ-lyon1.fr.
authors.forename: René
authors.initials: R
authors.lastname: Ferrera
authors.affiliation: Université Lyon 1, Lyon, France.
authors.forename: Souhila
authors.initials: S
authors.lastname: Benhabbouche
authors.affiliation: Université Lyon 1, Lyon, France.
authors.forename: Claire Crola
authors.initials: CC
authors.lastname: Da Silva
authors.affiliation: Université Lyon 1, Lyon, France.
authors.forename: Muhammad Rizwan
authors.initials: MR
authors.lastname: Alam
authors.affiliation: Université Lyon 1, Lyon, France; IHU OPERA and Service d'Explorations Fonctionnelles Cardiovasculaires and CIC de Lyon, Groupement Hospitalier Est, Hospices Civils of Lyon, Lyon, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Ovize
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D004195:Disease Models, Animal; D019157:Ischemic Preconditioning, Myocardial; D008297:Male; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar
chemical_list: D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore
keywords: controlled reperfusion; delayed reperfusion; mitochondria; permeability transition pore; postconditioning