Arterial carbon dioxide and bicarbonate rather than pH regulate cerebral blood flow in the setting of acute experimental metabolic alkalosis

Research output: Contribution to journalJournal articleResearchpeer-review

  • Caldwell, Hannah Grace
  • Connor A Howe
  • Carter J Chalifoux
  • Ryan L Hoiland
  • Jay M J R Carr
  • Courtney V Brown
  • Alexander Patrician
  • Joshua C Tremblay
  • Ronney B Panerai
  • Thompson G Robinson
  • Jatinder S Minhas
  • Philip N Ainslie

Cerebral blood flow (CBF) regulation is dependent on the integrative relationship between arterial PCO2 (PaCO2), pH and cerebrovascular tone; however, pre-clinical studies indicate that intrinsic sensitivity to pH, independent of changes in PaCO2 or intravascular bicarbonate ([HCO3]), principally influences cerebrovascular tone. Eleven healthy males completed a standardized cerebrovascular CO2 reactivity (CVR) test utilizing radial artery catheterization and Duplex ultrasound (CBF); consisting of matched stepwise iso-oxic alterations in PaCO2 (hypocapnia: –5, –10 mmHg; hypercapnia: +5, +10 mmHg) prior to and following i.v. sodium bicarbonate (NaHCO3; 8.4%, 50 mEq 50 mL–1) to elevate pH (7.408 ± 0.020 vs. 7.461 ± 0.030; P < 0.001) and [HCO3] (26.1 ± 1.4 vs. 29.3 ± 0.9 mEq L–1; P < 0.001). Absolute CBF was not different at each stage of CO2 reactivity (P = 0.629) following NaHCO3, irrespective of a higher pH (P < 0.001) at each matched stage of PaCO2 (P = 0.927). Neither hypocapnic (3.44 ± 0.92 vs. 3.44 ± 1.05% per mmHg PaCO2; P = 0.499), nor hypercapnic (7.45 ± 1.85 vs. 6.37 ± 2.23% per mmHg PaCO2; P = 0.151) reactivity to PaCO2 were altered pre- to post-NaHCO3. When indexed against arterial [H+], the relative hypocapnic CVR was higher (P = 0.019) and hypercapnic CVR was lower (P = 0.025) following NaHCO3, respectively. These changes in reactivity to [H+] were, however, explained by alterations in buffering between PaCO2 and arterial H+/pH consequent to NaHCO3. Lastly, CBF was higher (688 ± 105 vs. 732 ± 89 mL min–1, 7% ± 12%; P = 0.047) following NaHCO3 during isocapnic breathing providing support for a direct influence of HCO3 on cerebrovascular tone independent of PaCO2. These data indicate that in the setting of acute metabolic alkalosis, CBF is regulated by PaCO2 rather than arterial pH.

Original languageEnglish
JournalJournal of Physiology
Issue number5
Pages (from-to)1439-1457
Number of pages19
Publication statusPublished - 2021
Externally publishedYes

    Research areas

  • Acid–base balance, Cerebral blood flow, CO reactivity, Metabolic alkalosis, Sodium bicarbonate

ID: 255835961