Premium
Alterations in arterial CO 2 rather than pH affect the kinetics of neurovascular coupling in humans
Author(s) -
Caldwell Hannah G.,
Howe Connor A.,
Hoiland Ryan L.,
Carr Jay M.J.R.,
Chalifoux Carter J.,
Brown Courtney V.,
Patrician Alexander,
Tremblay Joshua C.,
Panerai Ronney B.,
Robinson Thompson G.,
Minhas Jatinder S.,
Ainslie Philip N.
Publication year - 2021
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jp281615
Subject(s) - kinetics , affect (linguistics) , neurovascular bundle , chemistry , coupling (piping) , biophysics , neuroscience , medicine , anatomy , biology , materials science , physics , psychology , communication , quantum mechanics , metallurgy
Key points We investigated the influence of arterial P C O 2( P aC O 2) with and without acute experimental metabolic alkalosis on neurovascular coupling (NVC). We assessed stepwise iso‐oxic alterations in P aC O 2prior to and following intravenous NaHCO 3 to acutely elevate arterial pH and [HCO 3 – ]. The NVC response was not altered following NaHCO 3 between stepwise P aC O 2stages; therefore, NVC is acutely mediated by P aC O 2rather than the prevailing arterial [H + ]/pH. The NVC response was attenuated by 27–38% with −10 mmHg P aC O 2and the absolute peak change was reduced by −19% with +10 mmHg P aC O 2irrespective of acutely elevated arterial pH/[HCO 3 – ]. The NVC kinetics (i.e. time to peak) were markedly slower with hypercapnia versus hypocapnia (24 ± 5 vs . 7 ± 5 s, respectively) likely indicating an influence of resting cerebrovascular tone on NVC responsiveness.Abstract 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 P C O 2( P aC O 2) 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, P aC O 2would 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 P aC O 2(hypocapnia: −5, −10 mmHg; hypercapnia: +5, +10 mmHg) prior to and following intravenous NaHCO 3 (8.4%, 50 mEq/50 ml) that elevated arterial pH (7.406 ± 0.019 vs . 7.457 ± 0.029; P < 0.001) and [HCO 3 – ] (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 P aC O 2(stage post hoc : all P < 0.05), this response was unaltered following NaHCO 3 (all P > 0.05) irrespective of the higher pH ( P = 0.002) at each matched stage of P aC O 2( P = 0.417). The absolute peak change was reduced by −19 ± 41% with +10 mmHg P aC O 2irrespective of acutely elevated arterial pH/[HCO 3 – ] (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 P aC O 2rather than arterial pH per se in the setting of acute metabolic alkalosis in humans.