Impact of hypocapnia and cerebral perfusion on orthostatic tolerance
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Bibliographic record
Abstract
Key points Vasovagal syncope (a common form of fainting) is frequently associated with excessive breathing and leads to reductions in carbon dioxide (hypocapnia) and cerebral hypoperfusion. The prevention of hypocapnia during orthostatic stress has been shown to improve orthostatic tolerance, but it still remains to be quantified in a larger population, with a more sustained orthostatic stress. Resting brain blood flow has been shown to impact orthostatic tolerance; however, the importance of resting brain blood flow per se in the pathophysiology of vasovagal syncope has not been clearly explicated. Our findings show that cerebral hypoperfusion either at rest or induced by hypocapnia at pre‐syncope do not impact on orthostatic tolerance, probably due to a compensatory increase in oxygen extraction of the brain. Abstract We examined two novel hypotheses: (1) that orthostatic tolerance (OT) would be prolonged when hyperventilatory‐induced hypocapnia (and hence cerebral hypoperfusion) was prevented; and (2) that pharmacological reductions in cerebral blood flow (CBF) at baseline would lower the ‘CBF reserve’, and ultimately reduce OT. In study 1 ( n = 24; aged 25 ± 4 years) participants underwent progressive lower‐body negative pressure (LBNP) until pre‐syncope; end‐tidal carbon dioxide ( ) was clamped at baseline levels (isocapnic trial) or uncontrolled. In study 2 ( n = 10; aged 25 ± 4 years), CBF was pharmacologically reduced by administration of indomethacin (INDO; 1.2 mg kg −1 ) or unaltered (placebo) followed by LBNP to pre‐syncope. Beat‐by‐beat measurements of middle cerebral artery blood flow velocity (MCAv; transcranial Doppler), heart rate (ECG), blood pressure (BP; Finometer) and end‐tidal gases were obtained continuously. In a subset of subjects’ arterial‐to‐jugular venous differences were obtained to examine the independent impact of hypocapnia or cerebral hypoperfusion (following INDO) on cerebral oxygen delivery and extraction. In study 1, during the isocapnic trial, was successfully clamped at baseline levels at pre‐syncope (38.3 ± 2.7 vs . 38.5 ± 2.5 mmHg respectively; P = 0.50). In the uncontrolled trial, at pre‐syncope was reduced by 10.9 ± 3.9 mmHg ( P ≤ 0.001). Compared to the isocapnic trial, the decline in mean MCAv was 15 ± 4 cm s −1 (35%; P ≤ 0.001) greater in the uncontrolled trial, yet the time to pre‐syncope was comparable between trials (544 ± 130 vs . 572 ± 180 s; P = 0.30). In study 2, compared to placebo, INDO reduced resting MCAv by 19 ± 4 cm s −1 (31%; P ≤ 0.001), but time to pre‐syncope remained similar between trials (placebo: 1123 ± 138 s vs . INDO: 1175 ± 212 s; P = 0.53). The brain extracted more oxygen in face of hypocapnia (34% to 53%) or cerebral hypoperfusion (34% to 57%) to compensate for reductions in delivery. In summary, cerebral hypoperfusion either at rest or induced by hypocapnia at pre‐syncope does not impact OT, probably due to a compensatory increase in oxygen extraction.
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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