Naloxone improves arterial blood pressure and hypoxic ventilatory depression, but not survival, of rats during acute hypoxia

Objective: To investigate the effects of naloxone and morphine during acute hypoxia. Design: Prospective, randomized animal study. Setting: University laboratory. Subjects: Twenty-eight adult male Sprague Dawley rats, weighing 300-350 g. Interventions: The rats were implanted with a femoral catheter and subcutan eous electrodes for electrocardiogram recording and were randomly assigned to receive morphine (5 mg/kg), naloxone (5 mg and 10 mg/kg), or normal sali ne (control) (n = 7 in each). Fifteen minutes after intraperitoneal injecti on of the drug, each rat was exposed to hypoxic gas (5% oxygen, 95% N-2) fo r 70 mins. Hypoxic survival time was measured. Mean arterial pressure (MAP) , arterial pH, PaCO2, Pao(2), and base excess were measured before injectio n (baseline), 14 mins after injection (HO), and 6 mins (H1), 33 mins (H2), and 48 mins (H3) after exposure to hypoxia. Measurements and Main Results: Hypoxic survival was similar between the nal oxone 5 mg/kg and control groups (p = .183), significantly tower in the nal oxone 10 mg/kg group (p <.01), and significantly higher in the morphine 5 m g/kg group (p < .05) compared with controls. MAP significantly decreased in all groups. However, at H2-H3, MAP was better preserved in both naloxone g roups and was lower in the morphine group compared with controls. Pace, was maintained higher at H0-H3 in the morphine group and lower at H2-H3 in bot h naloxone groups compared with controls. Conclusion: During acute hypoxia, naloxone preserves arterial blood pressur e and attenuates hypoxic ventilatory depression by antagonizing endogenous opiates, but it does not improve hypoxic survival. In contrast, morphine, w hich enhances the action of endogenous opiates, does improve hypoxic surviv al. The acute hypoxic tolerance of morphine may be partly attributable to a depression of oxygen consumption, increased cerebral blood flaw secondary to high PaCO2, and protective actions mediated by delta -oploid receptors.