Alterations in arterial CO2 rather than pH affect the kinetics of neurovascular coupling in humans

Research output: Contribution to journalJournal articleResearchpeer-review

  • Caldwell, Hannah Grace
  • Connor A Howe
  • Ryan L Hoiland
  • Jay M J R Carr
  • Carter J Chalifoux
  • Courtney V Brown
  • Alexander Patrician
  • Joshua C Tremblay
  • Ronney B Panerai
  • Thompson G Robinson
  • Jatinder S Minhas
  • Philip N Ainslie
Elevations in cerebral metabolism necessitate appropriate coordinated and localized increases in cerebral blood flow (i.e. neurovascular coupling; NVC). Recent pre-clinical work indicates that arterial PCO2 (PaCO2) mediates NVC independently of arterial/extracellular pH; this has yet to be experimentally tested in humans. The goal of this study was to investigate the hypotheses that: (1) the NVC response would be unaffected by acute experimentally elevated arterial pH; rather, PaCO2 would regulate any changes in NVC; and (2) stepwise respiratory alkalosis and acidosis would each progressively reduce the NVC response. Ten healthy males completed a standardized visual stimulus-evoked NVC test during matched stepwise iso-oxic alterations in PaCO2 (hypocapnia: −5, −10 mmHg; hypercapnia: +5, +10 mmHg) prior to and following intravenous NaHCO3 (8.4%, 50 mEq/50 ml) that elevated arterial pH (7.406 ± 0.019 vs. 7.457 ± 0.029; P < 0.001) and [HCO3] (26.2 ± 1.5 vs. 29.3 ± 0.9 mEq/l; P < 0.001). Although the NVC response was collectively attenuated by 27–38% with −10 mmHg PaCO2 (stage post hoc: all P < 0.05), this response was unaltered following NaHCO3 (all P > 0.05) irrespective of the higher pH (P = 0.002) at each matched stage of PaCO2 (P = 0.417). The absolute peak change was reduced by −19 ± 41% with +10 mmHg PaCO2 irrespective of acutely elevated arterial pH/[HCO3] (stage post hoc: P = 0.022). The NVC kinetics (i.e. time to peak) were markedly slower with hypercapnia versus hypocapnia (24 ± 5 vs. 7 ± 5 s, respectively; stage effect: P < 0.001). Overall, these findings indicate that temporal patterns in NVC are acutely regulated by PaCO2 rather than arterial pH per se in the setting of acute metabolic alkalosis in humans.
Original languageEnglish
JournalJournal of Physiology
Issue number15
Pages (from-to)3663-3676
Number of pages14
Publication statusPublished - 2021
Externally publishedYes

ID: 273078392