Desipramine Increases Genioglossus Activity and Reduces Upper Airway Collapsibility during Non-REM Sleep in Healthy Subjects
Bibliographic record
Abstract
Abstract Rationale Obstructive sleep apnea is a state-dependent disease. One of the key factors that triggers upper airway collapse is decreased pharyngeal dilator muscle activity during sleep. To date, there have not been effective methods to reverse pharyngeal hypotonia pharmacologically in sleeping humans. Objectives We tested the hypothesis that administration of desipramine 200 mg prevents the state-related reduction in genioglossus activity that occurs during sleep and thereby decreases pharyngeal collapsibility. Methods We conducted a placebo-controlled, double-blind, crossover trial with 10 healthy participants. Participants received active treatment or placebo in randomized order 2 hours before sleep in the physiology laboratory. Measurements and Main Results Genioglossus activity during wakefulness and sleep, genioglossus muscle responsiveness to negative epiglottic pressure, and upper airway collapsibility during passive and active conditions were compared between on- and off-drug states. Desipramine abolished the normal reduction of genioglossus activity from wakefulness to non-REM sleep that occurred on the placebo night. Specifically, tonic (median, 96% [86–120] vs. 75% [50–92] wakefulness; P = 0.01) but not phasic genioglossus activity was higher with desipramine compared with placebo. Upper airway collapsibility was also reduced with desipramine compared with placebo (−10.0 cm H2O [−15.2 to −5.8] vs. −8.1 cm H2O [−10.4 to −6.3]; P = 0.037). Conclusions Desipramine reduces the state-related drop in tonic genioglossus muscle activity that occurs from wakefulness to non-REM sleep and reduces airway collapsibility. These data provide a rationale for a new pharmacologic therapy for obstructive sleep apnea. Clinical trial registered with www.clinicaltrials.gov (NCT02428478).
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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 | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 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 | 0.001 | 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".