Influence of cerebral blood flow on central sleep apnea at high altitude

Keith R. Burgess*, Samuel J E Lucas, Kelly Shepherd, Andrew Dawson, Marianne Swart, Kate N. Thomas, Rebekah A I Lucas, Joseph Donnelly, Karen C. Peebles, Rishi Basnyat, Philip N. Ainslie

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)


Study Objectives: 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.

Design: The study was a randomized, placebo-controlled single-blind study.

Setting: A field study at 5,050 m in Nepal.

Patients or Participants: We studied 12 normal volunteers.

Interventions: Between days 5 to10 at high altitude, CBF velocity (CBFv) was increased by intravenous (IV) acetazolamide (10 mg/kg) and reduced by oral indomethacin (100 mg).

Measurements and 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 PaCO 2 or pH.

Conclusion: Our findings indicate an important role for cerebral blood flow regulation in the pathophysiology of central sleep apnea at high altitude.

Original languageEnglish
Pages (from-to)1679-1687
Number of pages9
Issue number10
Publication statusPublished - 1 Oct 2014
Externally publishedYes


  • Central sleep apnea
  • Cerebral blood flow
  • Cerebral vascular reactivity
  • High altitude
  • Ventilatory responses


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