The essential role of peripheral respiratory chemoreceptor inputs in maintaining breathing revealed when CO <sub>2</sub> stimulation of central chemoreceptors is diminished
Bibliographic record
Abstract
Key points Central sleep apnoea is a condition characterized by oscillations between apnoea and hyperpnoea during sleep, which can have many serous health implications. Each ventilatory overshoot following an apnoea attenuates peripheral chemoreceptor input which, in turn, has the potential to cause a further apnoea. In a decerebrate, vagotomized, in situ rat preparation, we show that central apnoeas can be overcome both physiologically (with high peripheral CO 2 ) and pharmacologically (with peripheral pituitary adenylate cyclase‐activating peptide). We also show that the central apnoeic threshold, i.e. the CO 2 level at which the animal stops breathing, can be lowered by increasing peripheral chemoreceptor stimulation. These data suggest that stimulation of peripheral chemoreceptors may prevent central apnoeas, re‐affirming the peripheral chemoreceptors as possible therapeutic targets for some sleep apnea phenotypes. Abstract Central sleep apnoea is a condition characterized by oscillations between apnoea and hyperpnoea during sleep. Studies in sleeping dogs suggest that withdrawal of peripheral chemoreceptor (carotid body) activation following transient ventilatory overshoots plays an essential role in causing apnoea, raising the possibility that sustaining carotid body activity during ventilatory overshoots may prevent apnoea. To test whether sustained peripheral chemoreceptor activation is sufficient to drive breathing, even in the absence of central chemoreceptor stimulation and vagal feedback, we used a vagotomized, decerebrate dual‐perfused in situ rat preparation in which the central and peripheral chemoreceptors are independently and artificially perfused with gas‐equilibrated medium. At varying levels of carotid body stimulation (CB P O2 / P CO2 : 40/60, 100/40, 200/15, 500/15 Torr), we decreased the brainstem perfusate P CO2 in 5 Torr steps while recording phrenic nerve activity to determine the central apnoeic thresholds. The central apnoeic thresholds decreased with increased carotid body stimulation. When the carotid bodies were strongly stimulated (CB 40/60), the apnoeic threshold was 3.6 ± 1.4 Torr P CO2 (mean ± SEM, n = 7). Stimulating carotid body afferent activity with either hypercapnia (60 Torr P CO2 ) or the neuropeptide pituitary adenylate cyclase‐activating peptide restored phrenic activity during central apnoea. We conclude that peripheral stimulation shifts the central apnoeic threshold to very hypocapnic levels that would likely increase the CO 2 reserve and have a protective effect on breathing. These data demonstrate that peripheral respiratory chemoreceptors are sufficient to stave off central apnoeas when the brainstem is perfused with low to no CO 2 .
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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 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 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".