Trans-cerebral HCO3- and PCO2 exchange during acute respiratory acidosis and exercise-induced metabolic acidosis in humans

Hannah G. Caldwell, Ryan Hoiland, Kurt J Smith, Patrice Brassard, Anthony R. Bain, Michael M. Tymko, Connor Howe, Jay MRJ Carr, Benjamin Stacey, Damian Bailey, Audrey Drapeau, Mypinder S. Sekhon, David B. MacLeod, Philip Ainslie

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This study investigated trans-cerebral internal jugular venous-arterial bicarbonate ([HCO3-]) and carbon dioxide tension (PCO2) exchange utilizing two separate interventions to induce acidosis: 1) acute respiratory acidosis via elevations in arterial PCO2 (PaCO2) (n = 39); and 2) metabolic acidosis via incremental cycling exercise to exhaustion (n = 24). During respiratory acidosis, arterial [HCO3-] increased by 0.15 ± 0.05 mmol ⋅ l-1 per mmHg elevation in PaCO2 across a wide physiological range (35 to 60 mmHg PaCO2; P < 0.001). The narrowing of the venous-arterial [HCO3-] and PCO2 differences with respiratory acidosis were both related to the hypercapnia-induced elevations in cerebral blood flow (CBF) (both P < 0.001; subset n = 27); thus, trans-cerebral [HCO3-] exchange (CBF × venous-arterial [HCO3-] difference) was reduced indicating a shift from net release toward net uptake of [HCO3-] (P = 0.004). Arterial [HCO3-] was reduced by -0.48 ± 0.15 mmol ⋅ l-1 per nmol ⋅ l-1 increase in arterial [H+] with exercise-induced acidosis (P < 0.001). There was no relationship between the venous-arterial [HCO3-] difference and arterial [H+] with exercise-induced acidosis or CBF; therefore, trans-cerebral [HCO3-] exchange was unaltered throughout exercise when indexed against arterial [H+] or pH (P = 0.933 and P = 0.896, respectively). These results indicate that increases and decreases in systemic [HCO3-] - during acute respiratory/exercise-induced metabolic acidosis, respectively - differentially affect cerebrovascular acid-base balance (via trans-cerebral [HCO3-] exchange).
Original languageEnglish
Pages (from-to)559-571
Number of pages13
JournalJournal of Cerebral Blood Flow and Metabolism
Issue number4
Early online date14 Dec 2021
Publication statusPublished - 1 Apr 2022


  • Acidosis
  • bicarbonate
  • carbon dioxide
  • exercise
  • trans-cerebral exchange


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