title: Influence of cerebral blood flow on central sleep apnea at high altitude.
abstract: OBJECTIVE
  To further our understanding of central sleep apnea (CSA) at high altitude during acclimatization, we tested the hypothesis that pharmacologically altering cerebral blood flow (CBF) would alter the severity of CSA at high altitude.
  
  
  METHODS
  The study was a randomized, placebo-controlled single-blind study.
  
  
  METHODS
  A field study at 5,050 m in Nepal.
  
  
  METHODS
  We studied 12 normal volunteers.
  
  
  METHODS
  Between days 5 to 10 at high altitude, CBF velocity (CBFv) was increased by intravenous (IV) acetazolamide (10 mg/kg) and reduced by oral indomethacin (100 mg).
  
  
  RESULTS
  Arterial blood gases, hypoxic and hypercapnic ventilatory responses, and CBFv and its reactivity to carbon dioxide were measured awake. Overnight polysomnography was performed. The central apnea-hypopnea index was elevated following administration of indomethacin (89.2 ± 43.7 to 112.5 ± 32.9 events/h; mean ± standard deviation; P < 0.05) and was reduced following IV acetazolamide (89.2 ± 43.7 to 47.1 ± 48.1 events/h; P < 0.001). Intravenous acetazolamide elevated CBFv at high altitude by 28% (95% confidence interval [CI]: 22-34%) but did not affect ventilatory responses. The elevation in CBFv was partly mediated via a selective rise in partial pressure of arterial carbon dioxide (PaCO2) (28 ± 4 to 31 ± 3 mm Hg) and an associated fall in pH (P < 0.01). Oral indomethacin reduced CBFv by 23% (95% CI: 16-30%), blunted CBFv reactivity, and increased the hypercapnic ventilatory response by 66% (95% CI: 30-102%) but had no effect on PaCO2 or pH.
  
  
  CONCLUSIONS
  Our findings indicate an important role for cerebral blood flow regulation in the pathophysiology of central sleep apnea at high altitude.
authors.affiliation: Peninsula Sleep Laboratory, Sydney, New South Wales, Australia and Department of Medicine, University of Sydney, Sydney, New South Wales, Australia.
authors.forename: Keith R
authors.initials: KR
authors.lastname: Burgess
authors.affiliation: University of Otago, Dunedin, New Zealand.
authors.forename: Samuel J E
authors.initials: SJ
authors.lastname: Lucas
authors.affiliation: Peninsula Sleep Laboratory, Sydney, New South Wales, Australia.
authors.forename: Kelly
authors.initials: K
authors.lastname: Shepherd
authors.affiliation: Peninsula Sleep Laboratory, Sydney, New South Wales, Australia.
authors.forename: Andrew
authors.initials: A
authors.lastname: Dawson
authors.affiliation: Peninsula Sleep Laboratory, Sydney, New South Wales, Australia.
authors.forename: Marianne
authors.initials: M
authors.lastname: Swart
authors.affiliation: University of Otago, Dunedin, New Zealand.
authors.forename: Kate N
authors.initials: KN
authors.lastname: Thomas
authors.affiliation: University of Otago, Dunedin, New Zealand.
authors.forename: Rebekah A I
authors.initials: RA
authors.lastname: Lucas
authors.affiliation: University of Otago, Dunedin, New Zealand.
authors.forename: Joseph
authors.initials: J
authors.lastname: Donnelly
authors.affiliation: University of Otago, Dunedin, New Zealand.
authors.forename: Karen C
authors.initials: KC
authors.lastname: Peebles
authors.affiliation: Nepal International Clinic, Kathmandu, Nepal and Banner Good Samaritan Medical Center, Phoenix, Arizona.
authors.forename: Rishi
authors.initials: R
authors.lastname: Basnyat
authors.affiliation: Centre for Heart, Lung and Vascular Health, School of Health and Exercise Sciences, University of British Columbia, Okanagan Campus, Canada.
authors.forename: Philip N
authors.initials: PN
authors.lastname: Ainslie
mesh_terms: D000064:Acclimatization / Q000502:physiology; D000086:Acetazolamide / Q000008:administration & dosage / Q000494:pharmacology; D061605:Administration, Intravenous; D000284:Administration, Oral; D000328:Adult; D000531:Altitude; D002245:Carbon Dioxide / Q000097:blood / Q000494:pharmacology; D002317:Cardiovascular Agents / Q000008:administration & dosage / Q000494:pharmacology; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology*; D005260:Female; D006801:Humans; D006935:Hypercapnia / Q000503:physiopathology; D000860:Hypoxia / Q000503:physiopathology; D007213:Indomethacin / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D017286:Polysomnography; D016037:Single-Blind Method; D020182:Sleep Apnea, Central / Q000503:physiopathology*; D014851:Wakefulness / Q000502:physiology; D055815:Young Adult
chemical_list: D002317:Cardiovascular Agents; D002245:Carbon Dioxide; D000086:Acetazolamide; D007213:Indomethacin
keywords: central sleep apnea; cerebral blood flow; cerebral vascular reactivity; high altitude; ventilatory responses