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.