Ventilatory and Cerebrovascular Responses to Hypercapnia in Pulmonary Arterial Hypertension
Bibliographic record
Abstract
BACKGROUND Patients with pulmonary arterial hypertension (PAH) exhibit excessive ventilation at rest and during exercise. This is generally attributed to an increased physiological dead space related to extensive vascular remodeling and ventilation‐perfusion mismatch as well as hyperventilation resulting in low arterial carbon dioxide partial pressure (PCO 2 ). However, mechanisms accounting for this hyperventilation remain elusive. We hypothesized that PAH patients exhibit enhanced central chemoreflex sensitivity, resulting in increased ventilator drive, hyperventilation and reduced cerebral blood flow. METHODS Central chemoreflex sensitivity was evaluated in 11 PAH patients and 11 healthy controls matched for age, sex and body mass index, using the modified hyperoxic hypercapnic rebreathing method. Participants underwent a 5‐minute period breathing room air. Then, they were asked to hyperventilate for one minute to an end‐tidal PCO 2 (P ET CO 2 ) of 20–25 mmHg, before they started to breathe in a rebreathing bag (air mixture containing 7% CO 2 and 93% O 2 ) until P ET CO 2 reached 60 mmHg. During this protocol, left middle cerebral artery mean flow velocity (MCAv mean ; transcranial Doppler), mean arterial pressure (MAP; finger photoplethysmography), P ET CO 2 and minute ventilation (V E ,) were continuously monitored. The linear regression slope of V E ‐P ET CO 2 characterized central chemoreflex sensitivity during the rebreathing period. Associations between central chemoreflex sensitivity, resting V E and MCAv mean were explored (Pearson's correlations). RESULTS Central chemoreflex sensitivity was significantly higher in PAH patients compared to controls (2.1 (0.3) vs 0.9 (0.2) L/min/mmHg; p=0.003). PAH patients also displayed lower P ET CO 2 (37 (5) vs 43 (5) mmHg; p=0.01) and increased V E (14 (2) vs 10 (2) L/min; p=0.0003) at baseline compared to controls. Central chemoreflex sensitivity correlated with resting V E (r=0.68; p=0.0005) and also inversely correlated with MCAv mean (r=−0.48; p=0.02), which was lower in PAH patients (59.3 (10.6) vs 74.2 (15.8) cm/s; p=0.01). CONCLUSION These results suggest that PAH patients exhibit reduced cerebral blood flow as a result of higher chemoreflex sensitivity and secondary hyperventilation. Alternatively, the reduction in cerebral blood flow induced by hypocapnia might decrease brain tissue carbon dioxide wash‐out, acidifying the cerebrospinal fluid and leading to a higher chemoreceptor stimulus and increased ventilation. Support or Funding Information Doctoral scholarship from Fond de Recherche du Québec ‐ Santé (FRQ‐S) to Simon Malenfant
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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 | 0.001 |
| 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) | 0.001 | 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".