title: Adenosine and opioid receptors do not trigger the cardioprotective effect of mild hypothermia.
abstract: Mild hypothermia (32°C-34°C) exerts a potent cardioprotection in animal models of myocardial infarction. Recently, it has been proposed that this beneficial effect is related to survival signaling. We, therefore, hypothesized that the well-known cardioprotective pathways dependent on adenosine and/or opioid receptors could be the trigger of hypothermia-induced salvage. Open-chest rabbits were accordingly exposed to 30 minutes of coronary artery occlusion (CAO) under normothermic (NT) or hypothermic ([HT] 32°C) conditions. In the latter, hypothermia was induced by total liquid ventilation with temperature-controlled perfluorocarbons in order to effect ultrafast cooling and to accurately control cardiac temperature. After 4 hours of reperfusion, infarct and no-reflow zone sizes were assessed and quantified as a percentage of the risk zone. In animals experiencing HT ischemia, the infarct size was dramatically reduced as compared to NT animals (9% ± 3% vs 55% ± 2% of the risk zone, respectively). Importantly, administration of opioid and adenosine receptor antagonists (naloxone [6 mg/kg iv] and 8-(p-sulfophenyl) theophylline [20 mg/kg iv], respectively) did not alter the infarct size or affect the cardioprotective effect of hypothermia. Doses of these 2 antagonists were appropriately chosen since they blunted infarct size reduction induced by selective opioid or adenosine receptor stimulation with morphine (0.3 mg/kg iv) or N               (6)-cyclopentyladenosine ([CPA] 100 μg/kg iv), respectively. Therefore, the cardioprotective effect of mild hypothermia is not triggered by either opioid or adenosine receptor activation, suggesting the involvement of other cardioprotective pathways.
authors: Université Paris-Est, Laboratoire de Pharmacologie, Faculté de Médecine, Créteil, France.
authors: Lys
authors: L
authors: Darbera
authors: Mourad
authors: M
authors: Chenoune
authors: Fanny
authors: F
authors: Lidouren
authors: Bijan
authors: B
authors: Ghaleh
authors: Michael V
authors: MV
authors: Cohen
authors: James M
authors: JM
authors: Downey
authors: Alain
authors: A
authors: Berdeaux
authors: Renaud
authors: R
authors: Tissier
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D005466:Fluorocarbons / Q000737:chemistry; D007036:Hypothermia, Induced / Q000379:methods*; D009020:Morphine / Q000494:pharmacology; D009203:Myocardial Infarction / Q000503:physiopathology / Q000628:therapy*; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D058915:Purinergic P1 Receptor Antagonists / Q000494:pharmacology; D011817:Rabbits; D011957:Receptors, Opioid / Q000187:drug effects / Q000378:metabolism*; D018047:Receptors, Purinergic P1 / Q000187:drug effects / Q000378:metabolism*; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology; D013997:Time Factors
chemical_list: D000701:Analgesics, Opioid; D005466:Fluorocarbons; D009292:Narcotic Antagonists; D058915:Purinergic P1 Receptor Antagonists; D011957:Receptors, Opioid; D018047:Receptors, Purinergic P1; D009270:Naloxone; C048599:N(6)-cyclopentyladenosine; D009020:Morphine; C031433:8-(4-sulfophenyl)theophylline; D013806:Theophylline; D000241:Adenosine