title: Hypoxemia, oxygen content, and the regulation of cerebral blood flow.
abstract: 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.
authors.affiliation: Centre for Heart, Lung and Vascular Health, School of Health and Exercise Sciences, University of British Columbia-Okanagan Campus, Kelowna, British Columbia, Canada; and ryanleohoiland@gmail.com.
authors.forename: Ryan L
authors.initials: RL
authors.lastname: Hoiland
authors.affiliation: Centre for Heart, Lung and Vascular Health, School of Health and Exercise Sciences, University of British Columbia-Okanagan Campus, Kelowna, British Columbia, Canada; and.
authors.forename: Anthony R
authors.initials: AR
authors.lastname: Bain
authors.affiliation: Centre for Heart, Lung and Vascular Health, School of Health and Exercise Sciences, University of British Columbia-Okanagan Campus, Kelowna, British Columbia, Canada; and.
authors.forename: Mathew G
authors.initials: MG
authors.lastname: Rieger
authors.affiliation: Neurovascular Research Laboratory, Research Institute of Science and Health, University of South Wales, Glamorgan, United Kingdom.
authors.forename: Damian M
authors.initials: DM
authors.lastname: Bailey
authors.affiliation: Centre for Heart, Lung and Vascular Health, School of Health and Exercise Sciences, University of British Columbia-Okanagan Campus, Kelowna, British Columbia, Canada; and Neurovascular Research Laboratory, Research Institute of Science and Health, University of South Wales, Glamorgan, United Kingdom.
authors.forename: Philip N
authors.initials: PN
authors.lastname: Ainslie
mesh_terms: D000064:Acclimatization; D000255:Adenosine Triphosphate / Q000378:metabolism; D000531:Altitude; D000532:Altitude Sickness / Q000097:blood / Q000503:physiopathology; D000818:Animals; D002536:Cerebral Arteries / Q000378:metabolism* / Q000503:physiopathology; D002560:Cerebrovascular Circulation; D006438:Hemodilution; D006454:Hemoglobins / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D000860:Hypoxia / Q000097:blood* / Q000503:physiopathology; D009569:Nitric Oxide / Q000378:metabolism; D010100:Oxygen / Q000097:blood*; D015398:Signal Transduction; D014664:Vasodilation
chemical_list: D006454:Hemoglobins; D009569:Nitric Oxide; D000255:Adenosine Triphosphate; C100003:deoxyhemoglobin; D010100:Oxygen
keywords: adenosine triphosphate; cerebral blood flow; cerebral oxygen delivery; hypoxia; nitric oxide