Evidence for direct <scp>CO<sub>2</sub></scp>‐mediated alterations in cerebral oxidative metabolism in humans
Hannah G. Caldwell, Ryan L. Hoiland, Anthony R. Bain, Connor A. Howe, Jay M. J. R. Carr, Travis D. Gibbons, Cody Durrer, Michael M. Tymko, Benjamin S. Stacey, Damian M. Bailey, Mypinder S. Sekhon, David B. MacLeod, Philip N. Ainslie
Abstract
Abstract Aim How the cerebral metabolic rates of oxygen and glucose utilization (CMRO 2 and CMR Glc , respectively) are affected by alterations in arterial PCO 2 (PaCO 2 ) 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 PaCO 2 ranging between 30 and 60 mmHg. The CMRO 2 and CMR Glc 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 CMRO 2 was altered by 0.5 mL × min −1 (95% CI: −0.6 to −0.3) per mmHg change in PaCO 2 ( p < 0.001) which corresponded to a 9.8% (95% CI: −13.2 to −6.5) change in CMRO 2 with a 9 mmHg change in PaCO 2 (inclusive of hypo‐ and hypercapnia). The CMR Glc 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 PaCO 2 . Conclusion Collectively, the CMRO 2 is altered by approximately 1% per mmHg change in PaCO 2 . Further, glucose is incompletely oxidized during hypercapnia, indicating reductions in CMRO 2 are either met by compensatory increases in nonoxidative glucose metabolism or explained by a reduction in total energy production.