Increasing cerebral blood flow reduces the severity of central sleep apnea at high altitude

Research output: Contribution to journalArticle

Authors

  • Keith R Burgess
  • Katie Me Burgess
  • Kate E Sprecher
  • Joseph Donnelly
  • Aparna S Basnet
  • Michael M Tymko
  • Trevor A Day
  • Kurt Jason Smith
  • Nia C S Lewis
  • Philip Ainslie

External organisations

  • Peninsula Sleep Laboratory, Sydney, New South Wales, Australia and Department of Medicine, University of Sydney, Sydney, New South Wales, Australia.
  • University of Birmingham, Birmingam/UNITED KINGDOM.
  • Peninsula Sleep Clinic.
  • University of Cambridge
  • Banner Good Samaritan Medical Centre.
  • Centre for Heart, Lung and Vascular Health, School of Health and Exercise Sciences, University of British Columbia, Okanagan Campus, Canada.
  • Department of Biology, Faculty of Science and Technology, Mount Royal University, Canada.
  • Cardiovascular Research Group, University of Western Australia, Australia.
  • University of British Columbia

Abstract

Earlier studies have indicated an important role for cerebral blood flow in the pathophysiology of central sleep apnea (CSA) at high altitude, but were not decisive. To test the hypothesis that pharmacologically altering cerebral blood flow (CBF) without altering arterial blood gas (ABGs) values would alter the severity of CSA at high altitude, we studied 11 healthy volunteers. (8M, 3F; 31{plus minus}7 years) in a randomized placebo-controlled single-blind study at 5,050 metres in Nepal. CBF was increased by intravenous (iv) acetazolamide (Az; 10mg/kg) plus iv dobutamine (Dob) infusion (2-5 ug/kg/min) and reduced by oral indomethacin (Indo; 100mg). ABG samples were collected and ventilatory responses to hypercapnia (HCVR) and hypoxia (HVR) were measured by rebreathing and steady-state techniques before and after drug/placebo. Duplex ultrasound of blood flow in the internal carotid and vertebral arteries was used to measure global CBF. The initial 3-4 hours of sleep were recorded by full polysomnography. Iv Az+Dob increased global CBF by 37{plus minus}15% compared to placebo (P<0.001), whereas it was reduced by 21{plus minus}8% by oral Indo (P<0.001). ABGs and HVR were unchanged in both interventions. HCVR was reduced by 28%{plus minus}43% (P=0.1) during iv Az{plus minus}Dob administration and was elevated by 23%{plus minus}30% (P=0.05) by Indomethacin. During iv Az+Dob, the CSA index fell from 140{plus minus}45 (control night) to 48{plus minus}37 events/hour of sleep (P<0.001). Oral Indo had no significant effect on CSA. We conclude that increasing cerebral blood flow reduced the severity of CSA at high altitude; the likely mechanism is via a reduction in the background stimulation of central chemoreceptors.

Details

Original languageEnglish
JournalJournal of Applied Physiology
Early online date1 Feb 2018
Publication statusE-pub ahead of print - 1 Feb 2018