title: Naloxone improves arterial blood pressure and hypoxic ventilatory depression, but not survival, of rats during acute hypoxia.
abstract: OBJECTIVE
  To investigate the effects of naloxone and morphine during acute hypoxia.
  
  
  METHODS
  Prospective, randomized animal study.
  
  
  METHODS
  University laboratory.
  
  
  METHODS
  Twenty-eight adult male Sprague Dawley rats, weighing 300-350 g.
  
  
  METHODS
  The rats were implanted with a femoral catheter and subcutaneous electrodes for electrocardiogram recording and were randomly assigned to receive morphine (5 mg/kg), naloxone (5 mg and 10 mg/kg), or normal saline (control) (n = 7 in each). Fifteen minutes after intraperitoneal injection of the drug, each rat was exposed to hypoxic gas (5% oxygen, 95% N2) for 70 mins. Hypoxic survival time was measured. Mean arterial pressure (MAP), arterial pH, Paco2, Pao2, and base excess were measured before injection (baseline), 14 mins after injection (H0), and 6 mins (H1), 33 mins (H2), and 48 mins (H3) after exposure to hypoxia.
  
  
  RESULTS
  Hypoxic survival was similar between the naloxone 5 mg/kg and control groups (p = .183), significantly lower in the naloxone 10 mg/kg group (p < .01), and significantly higher in the morphine 5 mg/kg group (p < .05) compared with controls. MAP significantly decreased in all groups. However, at H2-H3, MAP was better preserved in both naloxone groups and was lower in the morphine group compared with controls. Paco2 was maintained higher at H0-H3 in the morphine group and lower at H2-H3 in both naloxone groups compared with controls.
  
  
  CONCLUSIONS
  During acute hypoxia, naloxone preserves arterial blood pressure and attenuates hypoxic ventilatory depression by antagonizing endogenous opiates, but it does not improve hypoxic survival. In contrast, morphine, which enhances the action of endogenous opiates, does improve hypoxic survival. The acute hypoxic tolerance of morphine may be partly attributable to a depression of oxygen consumption, increased cerebral blood flow secondary to high Paco2, and protective actions mediated by delta-opioid receptors.
authors.affiliation: Department of Emergency & Critical Care Medicine, Niigata University School of Medicine, Niigata, Japan. endoh@med.niigata-u.ac.jp
authors.forename: H
authors.initials: H
authors.lastname: Endoh
authors.forename: T
authors.initials: T
authors.lastname: Honda
authors.forename: S
authors.initials: S
authors.lastname: Ohashi
authors.forename: K
authors.initials: K
authors.lastname: Shimoji
mesh_terms: D000208:Acute Disease; D000818:Animals; D001784:Blood Gas Analysis; D001794:Blood Pressure / Q000187:drug effects*; D002245:Carbon Dioxide / Q000097:blood; D002560:Cerebrovascular Circulation / Q000187:drug effects; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D000860:Hypoxia / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality* / Q000503:physiopathology; D008297:Male; D009020:Morphine / Q000494:pharmacology / Q000627:therapeutic use*; D009270:Naloxone / Q000494:pharmacology / Q000627:therapeutic use*; D009292:Narcotic Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D009294:Narcotics / Q000494:pharmacology / Q000627:therapeutic use*; D018847:Opioid Peptides / Q000187:drug effects; D010100:Oxygen / Q000097:blood; D010101:Oxygen Consumption / Q000187:drug effects; D011446:Prospective Studies; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D016019:Survival Analysis; D013997:Time Factors
chemical_list: D009292:Narcotic Antagonists; D009294:Narcotics; D018847:Opioid Peptides; D002245:Carbon Dioxide; D009270:Naloxone; D009020:Morphine; D010100:Oxygen