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 ( ) with and without acutely elevated arterial pH and bicarbonate (HCO 3 – ) on cerebral blood flow (CBF) regulation in the internal carotid artery and vertebral artery. We assessed stepwise iso‐oxic alterations in (i.e. cerebrovascular CO 2 reactivity) prior to and following i.v. sodium bicarbonate infusion (NaHCO 3 – ) to acutely elevate arterial pH and HCO 3 – . 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 NaHCO 3 – infusion (i.e. changes in buffering capacity). Total CBF was ∼7% higher following NaHCO 3 – infusion during isocapnic breathing providing initial evidence for a direct vasodilatory influence of HCO 3 – 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 (HCO 3 – ), principally influences cerebrovascular tone. Eleven healthy males completed a standardized cerebrovascular CO 2 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 (NaHCO 3 – ; 8.4%, 50 mEq 50 mL –1 ) to elevate pH (7.408 ± 0.020 vs . 7.461 ± 0.030; P < 0.001) and HCO 3 – (26.1 ± 1.4 vs . 29.3 ± 0.9 mEq L –1 ; P < 0.001). Absolute CBF was not different at each stage of CO 2 reactivity ( P = 0.629) following NaHCO 3 – , 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‐NaHCO 3 – . When indexed against arterial H + , the relative hypocapnic CVR was higher ( P = 0.019) and hypercapnic CVR was lower ( P = 0.025) following NaHCO 3 – , respectively. These changes in reactivity to H + were, however, explained by alterations in buffering between and arterial H + /pH consequent to NaHCO 3 – . Lastly, CBF was higher (688 ± 105 vs . 732 ± 89 mL min –1 , 7% ± 12%; P = 0.047) following NaHCO 3 – during isocapnic breathing providing support for a direct influence of HCO 3 – on cerebrovascular tone independent of . These data indicate that in the setting of acute metabolic alkalosis, CBF is regulated by rather than arterial pH.