Hypoxemia, oxygen content, and the regulation of cerebral blood flow

Ryan L Hoiland, Anthony R Bain, Mathew G Rieger, Damian M Bailey, Philip Ainslie

Research output: Contribution to journalArticlepeer-review


This review highlights the influence of oxygen (O2) availability on cerebral blood flow (CBF). Evidence for reductions in O2 content (CaO2 ) rather than arterial O2 tension (PaO2 ) as the chief regulator of cerebral vasodilation, with deoxyhemoglobin as the primary O2 sensor and upstream response effector, is discussed. We review in vitro and in vivo data to summarize the molecular mechanisms underpinning CBF responses during changes in CaO2 . We surmise that 1) during hypoxemic hypoxia in healthy humans (e.g., conditions of acute and chronic exposure to normobaric and hypobaric hypoxia), elevations in CBF compensate for reductions in CaO2 and thus maintain cerebral O2 delivery; 2) evidence from studies implementing iso- and hypervolumic hemodilution, anemia, and polycythemia indicate that CaO2 has an independent influence on CBF; however, the increase in CBF does not fully compensate for the lower CaO2 during hemodilution, and delivery is reduced; and 3) the mechanisms underpinning CBF regulation during changes in O2 content are multifactorial, involving deoxyhemoglobin-mediated release of nitric oxide metabolites and ATP, deoxyhemoglobin nitrite reductase activity, and the downstream interplay of several vasoactive factors including adenosine and epoxyeicosatrienoic acids. The emerging picture supports the role of deoxyhemoglobin (associated with changes in CaO2 ) as the primary biological regulator of CBF. The mechanisms for vasodilation therefore appear more robust during hypoxemic hypoxia than during changes in CaO2 via hemodilution. Clinical implications (e.g., disorders associated with anemia and polycythemia) and future study directions are considered.

Original languageEnglish
Pages (from-to)398-413
JournalAmerican Journal of Physiology - Regulatory, Integrative and Comparative Physiology
Issue number5
Publication statusPublished - 1 Mar 2016


  • Acclimatization
  • Adenosine Triphosphate
  • Altitude
  • Altitude Sickness
  • Animals
  • Cerebral Arteries
  • Cerebrovascular Circulation
  • Hemodilution
  • Hemoglobins
  • Homeostasis
  • Humans
  • Hypoxia
  • Nitric Oxide
  • Oxygen
  • Signal Transduction
  • Vasodilation


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