• 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, and Philip N Ainslie.
• Peninsula Sleep Laboratory, Sydney, New South Wales, Australia and Department of Medicine, University of Sydney, Sydney, New South Wales, Australia.
• Sleep. 2014 Oct 1;37(10):1679-87.

Study ObjectivesTo 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.DesignThe study was a randomized, placebo-controlled single-blind study.SettingA field study at 5,050 m in Nepal.Patients Or ParticipantsWe studied 12 normal volunteers.InterventionsBetween 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).Measurements And ResultsArterial 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.ConclusionOur findings indicate an important role for cerebral blood flow regulation in the pathophysiology of central sleep apnea at high altitude.© 2014 Associated Professional Sleep Societies, LLC.

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