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

The Journal of physiology 2021 Mar

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We investigated the influence of arterial P C O 2 ( P aC O 2 ) 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 P aC O 2 (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 P aC O 2 , indicating that CBF is acutely regulated by P aC O 2 rather than arterial pH. The cerebrovascular responses to changes in arterial H+ /pH were altered in keeping with the altered relationship between P aC O 2 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 P aC O 2 levels. Cerebral blood flow (CBF) regulation is dependent on the integrative relationship between arterial P C O 2 ( P aC O 2 ), pH and cerebrovascular tone; however, pre-clinical studies indicate that intrinsic sensitivity to pH, independent of changes in P aC O 2 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 P aC O 2 (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 aC O 2 (P = 0.927). Neither hypocapnic (3.44 ± 0.92 vs. 3.44 ± 1.05% per mmHg P aC O 2 ; P = 0.499), nor hypercapnic (7.45 ± 1.85 vs. 6.37 ± 2.23% per mmHg P aC O 2 ; P = 0.151) reactivity to P aC O 2 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 P aC O 2 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 P aC O 2 . These data indicate that in the setting of acute metabolic alkalosis, CBF is regulated by P aC O 2 rather than arterial pH. © 2021 The Authors. The Journal of Physiology © 2021 The Physiological Society.

Citation

Hannah G Caldwell, Connor A Howe, Carter J Chalifoux, Ryan L Hoiland, Jay M J R Carr, Courtney V Brown, Alexander Patrician, Joshua C Tremblay, Ronney B Panerai, Thompson G Robinson, Jatinder S Minhas, Philip N Ainslie. Arterial carbon dioxide and bicarbonate rather than pH regulate cerebral blood flow in the setting of acute experimental metabolic alkalosis. The Journal of physiology. 2021 Mar;599(5):1439-1457