Stability of cerebral metabolism and substrate availability in humans during hypoxia and hyperoxia

Philip N. Ainslie*, Andrew D. Shaw, Kurt J. Smith, Christopher K. Willie, Keita Ikeda, Joseph Graham, David B. Macleod

*Corresponding author for this work

    Research output: Contribution to journalArticlepeer-review

    45 Citations (Scopus)


    Characterization of the influence of oxygen availability on brain metabolism is an essential step toward a better understanding of brain energy homoeostasis and has obvious clinical implications. However, how brain metabolism depends on oxygen availability has not been clearly examined in humans. We therefore assessed the influence of oxygen on CBF (cerebral blood flow) and CMRO2 (cerebral metabolic rates for oxygen) and carbohydrates. PaO2 (arterial partial pressure of oxygen) was decreased for 15 min to ~60, ~44 and ~35 mmHg [to target a SaO2 (arterial oxygen saturation) of 90, 80 and 70% respectively], and elevated to ~320 and ~430 mmHg. Isocapnia was maintained during each trial. At the end of each stage, arterial-jugular venous differences and volumetric CBF were measured to directly calculate cerebral metabolic rates. During progressive hypoxaemia, elevations in CBF were correlated with the reductions in both SaO2 (R2 =0.54, P<0.05) and CaO2 (arterial oxygen content) (R2 =0.57, P<0.05). Despite markedly reduced CaO2, cerebral oxygen delivery was maintained by increased CBF. Cerebral metabolic rates for oxygen, glucose and lactate remained unaltered during progressive hypoxia. Consequently, cerebral glucose delivery was in excess of that required, and net lactate efflux increased slightly in severe hypoxia, as reflected by a small increase in jugular venous lactate. Progressive hyperoxia did not alter CBF, CaO2, substrate delivery or cerebral metabolism. In conclusion, marked elevations in CBF with progressive hypoxaemia and related reductions in CaO2 resulted in a well-maintained cerebral oxygen delivery. As such, cerebral metabolism is still supported almost exclusively by carbohydrate oxidation during severe levels of hypoxaemia.

    Original languageEnglish
    Pages (from-to)661-670
    Number of pages10
    JournalClinical Science
    Issue number9
    Publication statusPublished - 1 May 2014


    • Cerebral blood flow
    • Cerebral metabolism
    • Hyperoxia
    • Hypoxia
    • Oxygen saturation


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