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

Abstract

Cerebral blood flow (CBF) regulation is dependent on the integrative relationship between arterial <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:msub><mml:mi>P</mml:mi><mml:mrow><mml:mi>C</mml:mi><mml:msub><mml:mi>O</mml:mi><mml:mn>2</mml:mn></mml:msub></mml:mrow></mml:msub></mml:math> ( <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:msub><mml:mi>P</mml:mi><mml:mrow><mml:mi>aC</mml:mi><mml:msub><mml:mi>O</mml:mi><mml:mn>2</mml:mn></mml:msub></mml:mrow></mml:msub></mml:math> ), pH and cerebrovascular tone; however, pre-clinical studies indicate that intrinsic sensitivity to pH, independent of changes in <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:msub><mml:mi>P</mml:mi><mml:mrow><mml:mi>aC</mml:mi><mml:msub><mml:mi>O</mml:mi><mml:mn>2</mml:mn></mml:msub></mml:mrow></mml:msub></mml:math> 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 <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:msub><mml:mi>P</mml:mi><mml:mrow><mml:mi>aC</mml:mi><mml:msub><mml:mi>O</mml:mi><mml:mn>2</mml:mn></mml:msub></mml:mrow></mml:msub></mml:math> (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 <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:msub><mml:mi>P</mml:mi><mml:mrow><mml:mi>aC</mml:mi><mml:msub><mml:mi>O</mml:mi><mml:mn>2</mml:mn></mml:msub></mml:mrow></mml:msub></mml:math> (P = 0.927). Neither hypocapnic (3.44 ± 0.92 vs. 3.44 ± 1.05% per mmHg <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:msub><mml:mi>P</mml:mi><mml:mrow><mml:mi>aC</mml:mi><mml:msub><mml:mi>O</mml:mi><mml:mn>2</mml:mn></mml:msub></mml:mrow></mml:msub></mml:math> ; P = 0.499), nor hypercapnic (7.45 ± 1.85 vs. 6.37 ± 2.23% per mmHg <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:msub><mml:mi>P</mml:mi><mml:mrow><mml:mi>aC</mml:mi><mml:msub><mml:mi>O</mml:mi><mml:mn>2</mml:mn></mml:msub></mml:mrow></mml:msub></mml:math> ; P = 0.151) reactivity to <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:msub><mml:mi>P</mml:mi><mml:mrow><mml:mi>aC</mml:mi><mml:msub><mml:mi>O</mml:mi><mml:mn>2</mml:mn></mml:msub></mml:mrow></mml:msub></mml:math> 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 <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:msub><mml:mi>P</mml:mi><mml:mrow><mml:mi>aC</mml:mi><mml:msub><mml:mi>O</mml:mi><mml:mn>2</mml:mn></mml:msub></mml:mrow></mml:msub></mml:math> 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 <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:msub><mml:mi>P</mml:mi><mml:mrow><mml:mi>aC</mml:mi><mml:msub><mml:mi>O</mml:mi><mml:mn>2</mml:mn></mml:msub></mml:mrow></mml:msub></mml:math> . These data indicate that in the setting of acute metabolic alkalosis, CBF is regulated by <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:msub><mml:mi>P</mml:mi><mml:mrow><mml:mi>aC</mml:mi><mml:msub><mml:mi>O</mml:mi><mml:mn>2</mml:mn></mml:msub></mml:mrow></mml:msub></mml:math> rather than arterial pH.