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. 2024 Sep;240(9):e14197.
doi: 10.1111/apha.14197. Epub 2024 Jul 3.

Evidence for direct CO2 -mediated alterations in cerebral oxidative metabolism in humans

Hannah G Caldwell  1 , Ryan L Hoiland  1   2   3   4   5 , Anthony R Bain  6 , Connor A Howe  1 , Jay M J R Carr  1 , Travis D Gibbons  1 , Cody G Durrer  7 , Michael M Tymko  8   9 , Benjamin S Stacey  10 , Damian M Bailey  10 , Mypinder S Sekhon  4   5   8   11 , David B MacLeod  12 , Philip N Ainslie  1
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Evidence for direct CO2 -mediated alterations in cerebral oxidative metabolism in humans

Hannah G Caldwell et al. Acta Physiol (Oxf). 2024 Sep.

Abstract

Aim: How the cerebral metabolic rates of oxygen and glucose utilization (CMRO2 and CMRGlc, respectively) are affected by alterations in arterial PCO2 (PaCO2) is equivocal and therefore was the primary question of this study.

Methods: This retrospective analysis involved pooled data from four separate studies, involving 41 healthy adults (35 males/6 females). Participants completed stepwise steady-state alterations in PaCO2 ranging between 30 and 60 mmHg. The CMRO2 and CMRGlc were assessed via the Fick approach (CBF × arterial-internal jugular venous difference of oxygen or glucose content, respectively) utilizing duplex ultrasound of the internal carotid artery and vertebral artery to calculate cerebral blood flow (CBF).

Results: The CMRO2 was altered by 0.5 mL × min-1 (95% CI: -0.6 to -0.3) per mmHg change in PaCO2 (p < 0.001) which corresponded to a 9.8% (95% CI: -13.2 to -6.5) change in CMRO2 with a 9 mmHg change in PaCO2 (inclusive of hypo- and hypercapnia). The CMRGlc was reduced by 7.7% (95% CI: -15.4 to -0.08, p = 0.045; i.e., reduction in net glucose uptake) and the oxidative glucose index (ratio of oxygen to glucose uptake) was reduced by 5.6% (95% CI: -11.2 to 0.06, p = 0.049) with a + 9 mmHg increase in PaCO2.

Conclusion: Collectively, the CMRO2 is altered by approximately 1% per mmHg change in PaCO2. Further, glucose is incompletely oxidized during hypercapnia, indicating reductions in CMRO2 are either met by compensatory increases in nonoxidative glucose metabolism or explained by a reduction in total energy production.

Keywords: Fick principle; blood flow; carbon dioxide; cerebral metabolic rate of oxygen; metabolism; ultrasound.

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