Arterial carbon dioxide and bicarbonate rather than pH regulate cerebral blood flow in the setting of acute experimental metabolic alkalosis
- 18 January 2021
- journal article
- research article
- Published by Wiley in The Journal of Physiology
- Vol. 599 (5), 1439-1457
- https://doi.org/10.1113/jp280682
Abstract
Key points We investigated the influence of arterial () 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 (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 , indicating that CBF is acutely regulated by rather than arterial pH. The cerebrovascular responses to changes in arterial H+/pH were altered in keeping with the altered relationship between 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 levels. Abstract Cerebral blood flow (CBF) regulation is dependent on the integrative relationship between arterial (), pH and cerebrovascular tone; however, pre‐clinical studies indicate that intrinsic sensitivity to pH, independent of changes in 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 (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 (P = 0.927). Neither hypocapnic (3.44 ± 0.92 vs. 3.44 ± 1.05% per mmHg ; P = 0.499), nor hypercapnic (7.45 ± 1.85 vs. 6.37 ± 2.23% per mmHg ; P = 0.151) reactivity to 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 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 . These data indicate that in the setting of acute metabolic alkalosis, CBF is regulated by rather than arterial pH.Keywords
Funding Information
- Canada Research Chairs (F11‐02423)
- Dunhill Medical Trust (RTF97/0117)
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