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

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. [ABSTRACT FROM AUTHOR]