Acute stress augments obstructive apneas and related O<sub>2</sub>-desaturations in urethane-anesthetised rats <i>via</i> disruption of cholinergic modulation
Bibliographic record
Abstract
Obstructive sleep apnea (OSA) is a multifactorial respiratory disorder affecting nearly 1 billon of adults worldwide. Anomalies in respiratory control during sleep contribute to airway obstructions and recurrent desaturations; however, the origins of the problem are not well known. Stress disrupts brain function and increases the risk of OSA co-morbidities, including hypertension and obesity. Because, hypothalamic structures regulating the stress response also project to medullary areas regulating cardiorespiratory function and airway motor control, we hypothesised that exposure to a single stress session is suffcient to induce cardiorespiratory disturbances associated with OSA. Experiments were performed in urethane-anesthetised rats; this approach allows sleep-like brain state alternations with significant reductions in upper airway (genioglossus; GG), but not diaphragmatic (DIA), muscle tone during the transition from NREM-like to REM-like states. Adult male rats were either subjected to a 90 min session of immobilisation stress (n = 21) or handled briefly by the experimenter (n = 18). 24h later, rats were anesthetised (urethane, 1.6 g/kg; i.v.) and instrumented to monitor DIA and GG EMG. O2 saturation was measured by pulse oximetry (S pO2). Blood pressure was measured by an arterial catheter. Rats were placed in a supine position and respiratory airflow was measure by a temperature probe near the nares. Obstructive apneas were identified by the absence of airflow in the presence of DIA activity with a S pO2 drop greater than 3%. Stress did not affect distribution of sleep-like states or the state-related changes in phasic GG activity. However, stress augmented the incidence of obstructive apneas (0.5 vs 2.2 events/h; p = 0.05) and doubled the severity of desaturations associated with apneas (-6% vs -12% drop; p = 0.03). Pre-treatment with atropine (0.5 mg/kg) reduced obstructive apneas (drug effect: p = 0.04). Atropine blocked apnea-related O2 desaturations in stressed but not controls (apnea x stress x atropine: p = 0.04). Atropine treatment augmented GG activity; this effect was greater in NREM-like state, especially in stressed rats (atropine x state x stress: p = 0.05). We conclude that, in urethane anesthetised rats, stress disrupts cardiorespiratory control in ways that favor significant obstructive apneas. Disruption of cholinergic modulation of GG activity and cardiovascular function likely contributes to this process. These data point to an important factor in the onset of OSA. While the frequency of apneas was modest we propose that recurrent exposure to stressors or more significant events will worsen the condition over time. Supported by the Canadian Institutes of Health Research and the Foundation of the Québec Heart & Lung Institute. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".