Indomethacin‐induced impairment of regional cerebrovascular reactivity: implications for respiratory control
Bibliographic record
Abstract
Key points Anterior and posterior cerebral circulations have differential reactivity to changes in arterial blood gases, but the implications for the chemoreflex control of breathing are unclear. Indomethacin‐induced blunting of cerebrovascular flow responsiveness did not affect central or peripheral respiratory chemoreflex magnitude using steady‐state end‐tidal forcing techniques. Posterior reactivity was related to hypoxic ventilatory decline, suggesting that CO2 washout from central chemoreceptors modulates hypoxic ventilatory dynamics. Our data indicate that steady‐state end‐tidal forcing techniques reduce the arterial–venous gradients, attenuating the effect of brain blood flow on ventilatory responses. Our study confirms the importance of measuring posterior cerebrovasculature when investigating the link between cerebral blood flow and the chemical control of breathing. Abstract Cerebrovascular reactivity impacts CO2–[H+] washout at the central chemoreceptors and hence has marked influence on the control of ventilation. To date, the integration of cerebral blood flow (CBF) and ventilation has been investigated exclusively with measures of anterior CBF, which has a differential reactivity from the vertebrobasilar system and perfuses the brainstem. We hypothesized that: (1) posterior versus anterior CBF would have a stronger relationship to central chemoreflex magnitude during hypercapnia, and (2) that higher posterior reactivity would lead to a greater hypoxic ventilatory decline (HVD). End‐tidal forcing was used to induce steady‐state hyperoxic (300 mmHg ) hypercapnia (+3, +6 and +9 mmHg ) and isocapnic hypoxia (45 mmHg ) before and following pharmacological blunting (indomethacin; INDO; 1.45 ± 0.17 mg kg−1) of resting CBF and reactivity. In 22 young healthy volunteers, ventilation, intra‐cranial arterial blood velocities and extra‐cranial blood flows were measured during these challenges. INDO‐induced blunting of cerebrovascular flow responsiveness (CVR) to CO2 was unrelated to variability in ventilatory sensitivity during hyperoxic hypercapnia. Further results in a sub‐group of volunteers (n = 9) revealed that elevations of via end‐tidal forcing reduce arterial–jugular venous gradients, attenuating the effect of CBF on chemoreflex responses. During isocapnic hypoxia, vertebral artery CVR was related to the magnitude of HVD (R2 = 0.27; P < 0.04; n = 16), suggesting that CO2–[H+] washout from central chemoreceptors modulates hypoxic ventilatory dynamics. No relationships were apparent with anterior CVR. As higher posterior, but not anterior, CVR was linked to HVD, our study highlights the importance of measuring flow in posterior vessels to investigate CBF and ventilatory integration.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| 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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 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 itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".