title: Hypoxia impairs the arousal response to external resistive loading and airway occlusion during sleep.
abstract: OBJECTIVE
  Sustained hypoxia is a neurocognitive depressant, which has been shown to impair respiratory load sensation. Hypoxia has also been shown to impair arousal in animal models, but the effects of sustained hypoxia on arousal in humans have not been studied. The aim of this study was to assess the effects of sustained hypoxia on arousal from sleep in normal subjects.
  
  
  METHODS
  Twelve normal male subjects (age, 24.3 +/- 1.2 years; body mass index, 24.8 +/- 1.4 kg/m2) were studied during stable stage 2 non-rapid eye movement sleep on 2 separate nights 1 week apart.
  
  
  METHODS
  Sleep physiology laboratory.
  
  
  METHODS
  Normal healthy volunteers.
  
  
  METHODS
  Arousal responses to external resistive loads (18 cm H2O x L(-1) x sec(-1)) and occlusions were compared during room-air breathing following sustained normoxia and isocapnic hypoxia (SaO2 approximately 85%).
  
  
  RESULTS
  Time to arousal and minimum esophageal pressure preceding arousal were measured. Time to arousal was significantly increased following hypoxia compared with normoxia for resistive loads (24.6 + 4.4 seconds vs. 12.6 +/- 1.9 seconds, p = .007) but not occlusions. Minimum esophageal pressure prior to arousal was more negative following hypoxia for both external loads (-16.8 +/- 1.2 vs. -13.5 +/- 1.3 cm H2O, p = .035) and occlusions (-19.6 +/- 2.2 vs. -15.1 +/- 1.5 cm H2O, p = .029).
  
  
  CONCLUSIONS
  We conclude that sustained isocapnic hypoxia delays arousal to inspiratory loading during sleep and increases the respiratory arousal threshold. This has implications for disorders characterized by sustained nocturnal hypoxia, such as neuromuscular weakness, chronic obstructive pulmonary disease, obesity-hypoventilation syndrome, and severe obstructive sleep apnea.
authors.affiliation: Adelaide Institute for Sleep Health, Repatriation General Hospital, Daw Park, South Australia, Australia. michael.hlavac@cdhb.govt.nz
authors.forename: Michael C
authors.initials: MC
authors.lastname: Hlavac
authors.forename: Peter G
authors.initials: PG
authors.lastname: Catcheside
authors.forename: Rachel
authors.initials: R
authors.lastname: McDonald
authors.forename: Danny J
authors.initials: DJ
authors.lastname: Eckert
authors.forename: Samantha
authors.initials: S
authors.lastname: Windler
authors.forename: R Doug
authors.initials: RD
authors.lastname: McEvoy
mesh_terms: D000328:Adult; D000402:Airway Obstruction / Q000175:diagnosis / Q000453:epidemiology*; D001143:Arousal / Q000502:physiology*; D015992:Body Mass Index; D002245:Carbon Dioxide / Q000378:metabolism; D004569:Electroencephalography; D004947:Esophagus / Q000502:physiology; D006801:Humans; D000860:Hypoxia / Q000175:diagnosis* / Q000503:physiopathology*; D008297:Male; D010100:Oxygen / Q000378:metabolism; D011312:Pressure; D012720:Severity of Illness Index; D012894:Sleep Stages / Q000502:physiology*; D013997:Time Factors
chemical_list: D002245:Carbon Dioxide; D010100:Oxygen