Regulation of cerebral blood flow by arterial PCO2 independent of metabolic acidosis at 5050 m
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Regulation of cerebral blood flow by arterial PCO2 independent of metabolic acidosis at 5050 m. / Caldwell, Hannah Grace; Smith, Kurt J; Lewis, Nia C S; Hoiland, Ryan L; Willie, Christopher K; Lucas, Samuel J E; Stembridge, Michael; Burgess, Keith R; MacLeod, David B; Ainslie, Philip N.
I: Journal of Physiology, Bind 599, Nr. 14, 2021.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Regulation of cerebral blood flow by arterial PCO2 independent of metabolic acidosis at 5050 m
AU - Caldwell, Hannah Grace
AU - Smith, Kurt J
AU - Lewis, Nia C S
AU - Hoiland, Ryan L
AU - Willie, Christopher K
AU - Lucas, Samuel J E
AU - Stembridge, Michael
AU - Burgess, Keith R
AU - MacLeod, David B
AU - Ainslie, Philip N
N1 - Publisher Copyright: © 2021 The Authors. The Journal of Physiology © 2021 The Physiological Society
PY - 2021
Y1 - 2021
N2 - 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.
AB - 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.
KW - Acetazolamide
KW - Acid-base balance
KW - Cerebral blood flow
KW - CO reactivity
KW - High altitude
KW - Metabolic acidosis
KW - Sodium bicarbonate
UR - http://www.scopus.com/inward/record.url?scp=85108415903&partnerID=8YFLogxK
U2 - 10.1113/JP281446
DO - 10.1113/JP281446
M3 - Journal article
C2 - 34047356
AN - SCOPUS:85108415903
VL - 599
JO - The Journal of Physiology
JF - The Journal of Physiology
SN - 0022-3751
IS - 14
ER -
ID: 273698392