Key points
We investigated the influence of arterial PnormalCO2 (PnormalaCO2) with and without acutely elevated arterial pH and bicarbonate ([HCO3–]) on cerebral blood flow (CBF) regulation in the internal carotid artery and vertebral artery.
We assessed stepwise iso‐oxic alterations in PnormalaCO2 (i.e. cerebrovascular CO2 reactivity) prior to and following i.v. sodium bicarbonate infusion (NaHCO3–) to acutely elevate arterial pH and [HCO3–].
Total CBF was unchanged irrespective of a higher arterial pH at each matched stage of PnormalaCO2, indicating that CBF is acutely regulated by PnormalaCO2 rather than arterial pH.
The cerebrovascular responses to changes in arterial H+/pH were altered in keeping with the altered relationship between PnormalaCO2 and H+/pH following NaHCO3– infusion (i.e. changes in buffering capacity).
Total CBF was ∼7% higher following NaHCO3– infusion during isocapnic breathing providing initial evidence for a direct vasodilatory influence of HCO3– independent of PnormalaCO2 levels.
Abstract
Cerebral blood flow (CBF) regulation is dependent on the integrative relationship between arterial PnormalCO2 (PnormalaCO2), pH and cerebrovascular tone; however, pre‐clinical studies indicate that intrinsic sensitivity to pH, independent of changes in PnormalaCO2 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 PnormalaCO2 (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 PnormalaCO2 (P = 0.927). Neither hypocapnic (3.44 ± 0.92 vs. 3.44 ± 1.05% per mmHg PnormalaCO2; P = 0.499), nor hypercapnic (7.45 ± 1.85 vs. 6.37 ± 2.23% per mmHg PnormalaCO2; P = 0.151) reactivity to PnormalaCO2 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 PnormalaCO2 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 PnormalaCO2. These data indicate that in the setting of acute metabolic alkalosis, CBF is regulated by PnormalaCO2 rather than arterial pH.