Steady-state cerebral blood flow regulation at altitude: interaction between oxygen and carbon dioxide

Hailey C. Lafave, Shaelynn M. Zouboules, Marina A. James, Graeme M. Purdy, Jordan L. Rees, Craig D. Steinback, Peter Ondrus, Tom D. Brutsaert, Heidi E. Nysten, Cassandra E. Nysten, Ryan L. Hoiland, Mingma T. Sherpa, Trevor A. Day

Research output: Contribution to journalArticlepeer-review

17 Scopus citations


High-altitude ascent imposes a unique cerebrovascular challenge due to two opposing blood gas chemostimuli. Specifically, hypoxia causes cerebral vasodilation, whereas respiratory-induced hypocapnia causes vasoconstriction. The conflicting nature of these two superimposed chemostimuli presents a challenge in quantifying cerebrovascular reactivity (CVR) in chronic hypoxia. During incremental ascent to 4240 m over 7 days in the Nepal Himalaya, we aimed to (a) characterize the relationship between arterial blood gas stimuli and anterior, posterior and global (g)CBF, (b) develop a novel index to quantify cerebral blood flow (CBF) in relation to conflicting steady-state chemostimuli, and (c) assess these relationships with cerebral oxygenation (rSO2). On rest days during ascent, participants underwent supine resting measures at 1045 m (baseline), 3440 m (day 3) and 4240 m (day 7). These measures included pressure of arterial (Pa)CO2, PaO2, arterial O2 saturation (SaO2; arterial blood draws), unilateral anterior, posterior and gCBF (duplex ultrasound; internal carotid artery [ICA] and vertebral artery [VA], gCBF [{ICA + VA} × 2], respectively) and rSO2 (near-infrared spectroscopy). We developed a novel stimulus index (SI), taking into account both chemostimuli (PaCO2/SaO2). Subsequently, CBF was indexed against the SI to assess steady-state cerebrovascular responsiveness (SS-CVR). When both competing chemostimuli are taken into account, (a) SS-CVR was significantly higher in ICA, VA and gCBF at 4240 m compared to lower altitudes, (b) delta SS-CVR with ascent (1045 m vs. 4240 m) was higher in ICA vs. VA, suggesting regional differences in CBF regulation, and (c) ICA SS-CVR was strongly and positively correlated (r = 0.79) with rSO2 at 4240 m.

Original languageEnglish (US)
Pages (from-to)2529-2544
Number of pages16
JournalEuropean Journal of Applied Physiology
Issue number11-12
StatePublished - Dec 1 2019


  • Cerebral blood flow
  • Cerebrovascular reactivity
  • High altitude
  • Hypocapnia
  • Hypoxia

ASJC Scopus subject areas

  • Orthopedics and Sports Medicine
  • Public Health, Environmental and Occupational Health
  • Physiology (medical)


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