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Regulation of cerebral blood flow by arterial PCO2 independent of metabolic acidosis at 5050 m.

Publication ,  Journal Article
Caldwell, HG; Smith, KJ; Lewis, NCS; Hoiland, RL; Willie, CK; Lucas, SJE; Stembridge, M; Burgess, KR; MacLeod, DB; Ainslie, PN
Published in: J Physiol
July 2021

KEY POINTS: We investigated the influence of arterial PCO2 (PaCO2 ) with and without experimentally altered pH on cerebral blood flow (CBF) regulation at sea level and with acclimatization to 5050 m. At sea level and high altitude, we assessed stepwise alterations in PaCO2 following metabolic acidosis (via 2 days of oral acetazolamide; ACZ) with and without acute restoration of pH (via intravenous sodium bicarbonate; ACZ+HCO3- ). Total resting CBF was unchanged between trials at each altitude even though arterial pH and [HCO3- ] (i.e. buffering capacity) were effectively altered. The cerebrovascular responses to changes in arterial [H+ ]/pH were consistent with the altered relationship between PaCO2 and [H+ ]/pH following ACZ at high altitude (i.e. leftward x-intercept shifts). Absolute cerebral blood velocity (CBV) and the sensitivity of CBV to PaCO2 was unchanged between trials at high altitude, indicating that CBF is acutely regulated by PaCO2 rather than arterial pH. ABSTRACT: Alterations in acid-base balance with progressive acclimatization to high altitude have been well-established. However, how respiratory alkalosis and the resultant metabolic compensation interact to regulate cerebral blood flow (CBF) is uncertain. We addressed this via three separate experimental trials at sea level and following partial acclimatization (14 to 20 days) at 5050 m; involving: (1) resting acid-base balance (control); (2) following metabolic acidosis via 2 days of oral acetazolamide at 250 mg every 8 h (ACZ; pH: Δ -0.07 ± 0.04 and base excess: Δ -5.7 ± 1.9 mEq⋅l-1 , trial effects: P < 0.001 and P < 0.001, respectively); and (3) after acute normalization of arterial acidosis via intravenous sodium bicarbonate (ACZ + HCO3- ; pH: Δ -0.01 ± 0.04 and base excess: Δ -1.5 ± 2.1 mEq⋅l-1 , trial effects: P = 1.000 and P = 0.052, respectively). Within each trial, we utilized transcranial Doppler ultrasound to assess the cerebral blood velocity (CBV) response to stepwise alterations in arterial PCO2 (PaCO2 ), i.e. cerebrovascular CO2 reactivity. Resting CBF (via Duplex ultrasound) was unaltered between trials within each altitude, indicating that respiratory compensation (i.e. Δ -3.4 ± 2.3 mmHg PaCO2 , trial effect: P < 0.001) was sufficient to offset any elevations in CBF induced via the ACZ-mediated metabolic acidosis. Between trials at high altitude, we observed consistent leftward shifts in both the PaCO2 -pH and CBV-pH responses across the CO2 reactivity tests with experimentally reduced arterial pH via ACZ. When indexed against PaCO2 - rather than pH - the absolute CBV and sensitivity of CBV-PaCO2 was unchanged between trials at high altitude. Taken together, following acclimatization, CO2 -mediated changes in cerebrovascular tone rather than arterial [H+ ]/pH is integral to CBF regulation at high altitude.

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Published In

J Physiol

DOI

EISSN

1469-7793

Publication Date

July 2021

Volume

599

Issue

14

Start / End Page

3513 / 3530

Location

England

Related Subject Headings

  • Physiology
  • Humans
  • Cerebrovascular Circulation
  • Carbon Dioxide
  • Blood Flow Velocity
  • Altitude
  • Acidosis
  • Acclimatization
  • 42 Health sciences
  • 32 Biomedical and clinical sciences
 

Citation

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Caldwell, H. G., Smith, K. J., Lewis, N. C. S., Hoiland, R. L., Willie, C. K., Lucas, S. J. E., … Ainslie, P. N. (2021). Regulation of cerebral blood flow by arterial PCO2 independent of metabolic acidosis at 5050 m. J Physiol, 599(14), 3513–3530. https://doi.org/10.1113/JP281446
Caldwell, Hannah G., Kurt J. Smith, Nia C. S. Lewis, Ryan L. Hoiland, Christopher K. Willie, Samuel J. E. Lucas, Michael Stembridge, Keith R. Burgess, David B. MacLeod, and Philip N. Ainslie. “Regulation of cerebral blood flow by arterial PCO2 independent of metabolic acidosis at 5050 m.J Physiol 599, no. 14 (July 2021): 3513–30. https://doi.org/10.1113/JP281446.
Caldwell HG, Smith KJ, Lewis NCS, Hoiland RL, Willie CK, Lucas SJE, et al. Regulation of cerebral blood flow by arterial PCO2 independent of metabolic acidosis at 5050 m. J Physiol. 2021 Jul;599(14):3513–30.
Caldwell, Hannah G., et al. “Regulation of cerebral blood flow by arterial PCO2 independent of metabolic acidosis at 5050 m.J Physiol, vol. 599, no. 14, July 2021, pp. 3513–30. Pubmed, doi:10.1113/JP281446.
Caldwell HG, Smith KJ, Lewis NCS, Hoiland RL, Willie CK, Lucas SJE, Stembridge M, Burgess KR, MacLeod DB, Ainslie PN. Regulation of cerebral blood flow by arterial PCO2 independent of metabolic acidosis at 5050 m. J Physiol. 2021 Jul;599(14):3513–3530.
Journal cover image

Published In

J Physiol

DOI

EISSN

1469-7793

Publication Date

July 2021

Volume

599

Issue

14

Start / End Page

3513 / 3530

Location

England

Related Subject Headings

  • Physiology
  • Humans
  • Cerebrovascular Circulation
  • Carbon Dioxide
  • Blood Flow Velocity
  • Altitude
  • Acidosis
  • Acclimatization
  • 42 Health sciences
  • 32 Biomedical and clinical sciences