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

Key points We investigated the influence of arterial PCO2 (PaCO2) 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 PaCO2 (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 PaCO2, indicating that CBF is acutely regulated by PaCO2 rather than arterial pH. The cerebrovascular responses to changes in arterial H+/pH were altered in keeping with the altered relationship between PaCO2 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 PaCO2 levels. 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