Arterial carbon dioxide and bicarbonate rather than pH regulate cerebral blood flow in the setting of acute experimental metabolic alkalosis. (18th January 2021)

• Record Type: Journal Article
• Authors: Caldwell, Hannah G.; Howe, Connor A.; Chalifoux, Carter J.; Hoiland, Ryan L.; Carr, Jay M. J. R.; Brown, Courtney V.; Patrician, Alexander; Tremblay, Joshua C.; Panerai, Ronney B.; Robinson, Thompson G.; Minhas, Jatinder S.; Ainslie, Philip N.
• Is Part Of: Journal of physiology. Volume 599:Number 5(2021)
• Page Start: 1439
• Page End: 1457
• Publication Date: 2021-01-18
• Subjects: acid–base balance -- cerebral blood flow -- CO2 reactivity -- metabolic alkalosis -- sodium bicarbonate; Physiology -- Periodicals; 612.005
• DOI: 10.1113/JP280682
• Languages: English
• ISSNs: 0022-3751

Abstract

Abstract : Key points: 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. Abstract: 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. Key points: 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.