title: Rapid cooling preserves the ischaemic myocardium against mitochondrial damage and left ventricular dysfunction.
abstract: OBJECTIVE
  We investigated whether rapid cooling instituted by total liquid ventilation (TLV) improves cardiac and mitochondrial function in rabbits submitted to ischaemia-reperfusion.
  
  
  RESULTS
  Rabbits were chronically instrumented with a coronary artery occluder and myocardial ultrasonic crystals for assessment of segment length-shortening. Two weeks later they were re-anaesthetized and underwent either a normothermic 30-min coronary artery occlusion (CAO) (Control group, n = 7) or a comparable CAO with cooling initiated by a 10-min hypothermic TLV and maintained by a cold blanket placed on the skin. Cooling was initiated after 5 or 15 min of CAO (Hypo-TLV and Hypo-TLV(15') groups, n = 6 and 5, respectively). A last group underwent normothermic TLV during CAO (Normo-TLV group, n = 6). Wall motion was measured in the conscious state over three days of reperfusion before infarct size evaluation and histology. Additional experiments were done for myocardial sampling in anaesthetized rabbits for mitochondrial studies. The Hypo-TLV procedure induced a rapid decrease in myocardial temperature to 32-34 degrees C. Throughout reperfusion, segment length-shortening was significantly increased in Hypo-TLV and Hypo-TLV(15') vs. Control and Normo-TLV (15.1 +/- 3.3%, 16.4 +/- 2.3%, 1.8 +/- 0.6%, and 1.1 +/- 0.8% at 72 h, respectively). Infarct sizes were also considerably attenuated in Hypo-TLV and Hypo-TLV(15') vs. Control and Normo-TLV (4 +/- 1%, 11 +/- 5%, 39 +/- 2%, and 42 +/- 5% infarction of risk zones, respectively). Mitochondrial function in myocardial samples obtained at the end of ischaemia or after 10 min of reperfusion was improved by Hypo-TLV with respect to ADP-stimulated respiration and calcium-induced opening of mitochondrial permeability transition pores (mPTP). Calcium concentration opening mPTP was, e.g., increased at the end of ischaemia in the risk zone in Hypo-TLV vs. Control (157 +/- 12 vs. 86 +/- 12 microM). Histology and electron microscopy also revealed better preservation of lungs and of cardiomyocyte ultrastructure in Hypo-TLV when compared with Control.
  
  
  CONCLUSIONS
  Institution of rapid cooling by TLV during ischaemia reduces infarct size as well as other sequelae of ischaemia, such as post-ischaemic contractile and mitochondrial dysfunction.
authors.affiliation: INSERM U955, Equipe 3, 94010 Créteil cedex, France.
authors.forename: Renaud
authors.initials: R
authors.lastname: Tissier
authors.forename: Nicolas
authors.initials: N
authors.lastname: Couvreur
authors.forename: Bijan
authors.initials: B
authors.lastname: Ghaleh
authors.forename: Patrick
authors.initials: P
authors.lastname: Bruneval
authors.forename: Fanny
authors.initials: F
authors.lastname: Lidouren
authors.forename: Didier
authors.initials: D
authors.lastname: Morin
authors.forename: Roland
authors.initials: R
authors.lastname: Zini
authors.forename: Alain
authors.initials: A
authors.lastname: Bize
authors.forename: Mourad
authors.initials: M
authors.lastname: Chenoune
authors.forename: Marie-France
authors.initials: MF
authors.lastname: Belair
authors.forename: Chantal
authors.initials: C
authors.lastname: Mandet
authors.forename: Martine
authors.initials: M
authors.lastname: Douheret
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Dubois-Rande
authors.forename: James C
authors.initials: JC
authors.lastname: Parker
authors.forename: Michael V
authors.initials: MV
authors.lastname: Cohen
authors.forename: James M
authors.initials: JM
authors.lastname: Downey
authors.forename: Alain
authors.initials: A
authors.lastname: Berdeaux
mesh_terms: D000244:Adenosine Diphosphate / Q000378:metabolism; D000818:Animals; D001512:Bedding and Linens; D002118:Calcium / Q000378:metabolism; D004195:Disease Models, Animal; D006439:Hemodynamics; D007036:Hypothermia, Induced / Q000295:instrumentation / Q000379:methods; D021061:Liquid Ventilation; D008297:Male; D008929:Mitochondria, Heart / Q000378:metabolism / Q000473:pathology*; D033681:Mitochondrial Membrane Transport Proteins / Q000378:metabolism; D000083162:Mitochondrial Permeability Transition Pore; D009200:Myocardial Contraction; D017202:Myocardial Ischemia / Q000150:complications / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D011817:Rabbits; D015427:Reperfusion Injury / Q000209:etiology / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D013997:Time Factors; D018487:Ventricular Dysfunction, Left / Q000209:etiology / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*
chemical_list: D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D000244:Adenosine Diphosphate; D002118:Calcium