Arterial carbon dioxide and bicarbonate rather than pH regulate cerebral blood flow in the setting of acute experimental metabolic alkalosis
Why this work is in the frame
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Bibliographic record
Abstract
Key points We investigated the influence of arterial ( ) with and without acutely elevated arterial pH and bicarbonate ([HCO 3 – ]) on cerebral blood flow (CBF) regulation in the internal carotid artery and vertebral artery. We assessed stepwise iso‐oxic alterations in (i.e. cerebrovascular CO 2 reactivity) prior to and following i.v. sodium bicarbonate infusion (NaHCO 3 – ) to acutely elevate arterial pH and [HCO 3 – ]. Total CBF was unchanged irrespective of a higher arterial pH at each matched stage of , indicating that CBF is acutely regulated by rather than arterial pH. The cerebrovascular responses to changes in arterial H + /pH were altered in keeping with the altered relationship between and H + /pH following NaHCO 3 – infusion (i.e. changes in buffering capacity). Total CBF was ∼7% higher following NaHCO 3 – infusion during isocapnic breathing providing initial evidence for a direct vasodilatory influence of HCO 3 – independent of levels. Abstract Cerebral blood flow (CBF) regulation is dependent on the integrative relationship between arterial ( ), pH and cerebrovascular tone; however, pre‐clinical studies indicate that intrinsic sensitivity to pH, independent of changes in or intravascular bicarbonate ([HCO 3 – ]), principally influences cerebrovascular tone. Eleven healthy males completed a standardized cerebrovascular CO 2 reactivity (CVR) test utilizing radial artery catheterization and Duplex ultrasound (CBF); consisting of matched stepwise iso‐oxic alterations in (hypocapnia: –5, –10 mmHg; hypercapnia: +5, +10 mmHg) prior to and following i.v. sodium bicarbonate (NaHCO 3 – ; 8.4%, 50 mEq 50 mL –1 ) to elevate pH (7.408 ± 0.020 vs . 7.461 ± 0.030; P < 0.001) and [HCO 3 – ] (26.1 ± 1.4 vs . 29.3 ± 0.9 mEq L –1 ; P < 0.001). Absolute CBF was not different at each stage of CO 2 reactivity ( P = 0.629) following NaHCO 3 – , irrespective of a higher pH ( P < 0.001) at each matched stage of ( P = 0.927). Neither hypocapnic (3.44 ± 0.92 vs . 3.44 ± 1.05% per mmHg ; P = 0.499), nor hypercapnic (7.45 ± 1.85 vs . 6.37 ± 2.23% per mmHg ; P = 0.151) reactivity to were altered pre‐ to post‐NaHCO 3 – . When indexed against arterial [H + ], the relative hypocapnic CVR was higher ( P = 0.019) and hypercapnic CVR was lower ( P = 0.025) following NaHCO 3 – , respectively. These changes in reactivity to [H + ] were, however, explained by alterations in buffering between and arterial H + /pH consequent to NaHCO 3 – . Lastly, CBF was higher (688 ± 105 vs . 732 ± 89 mL min –1 , 7% ± 12%; P = 0.047) following NaHCO 3 – during isocapnic breathing providing support for a direct influence of HCO 3 – on cerebrovascular tone independent of . These data indicate that in the setting of acute metabolic alkalosis, CBF is regulated by rather than arterial pH.
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Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it