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 ]) 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 reactivity) prior to and following i.v. sodium bicarbonate infusion (NaHCO ) to acutely elevate arterial pH and [HCO ]. 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 infusion (i.e. changes in buffering capacity). Total CBF was ∼7% higher following NaHCO infusion during isocapnic breathing providing initial evidence for a direct vasodilatory influence of HCO 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 ]), principally influences cerebrovascular tone. Eleven healthy males completed a standardized cerebrovascular CO 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 ; 8.4%, 50 mEq 50 mL ) to elevate pH (7.408 ± 0.020 vs. 7.461 ± 0.030; P < 0.001) and [HCO ] (26.1 ± 1.4 vs. 29.3 ± 0.9 mEq L ; P < 0.001). Absolute CBF was not different at each stage of CO reactivity (P = 0.629) following NaHCO , 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 . When indexed against arterial [H ], the relative hypocapnic CVR was higher (P = 0.019) and hypercapnic CVR was lower (P = 0.025) following NaHCO , respectively. These changes in reactivity to [H ] were, however, explained by alterations in buffering between and arterial H /pH consequent to NaHCO . Lastly, CBF was higher (688 ± 105 vs. 732 ± 89 mL min , 7% ± 12%; P = 0.047) following NaHCO during isocapnic breathing providing support for a direct influence of HCO on cerebrovascular tone independent of . These data indicate that in the setting of acute metabolic alkalosis, CBF is regulated by rather than arterial pH.