A new animal model of obstructive sleep apnea responding to continuous positive airway pressure

Abstract

Study objectives: An improved animal model of obstructive sleep apnea (OSA) is needed for the development of effective pharmacotherapies. In humans, flexion of the neck and a supine position, two main pathogenic factors during human sleep, are associated with substantially greater OSA severity. We postulated that these two factors might generate OSA in animals.

Design: We developed a restraining device for conditioning to investigate the effect of the combination of 2 body positions-prone (P) or supine (S)-and 2 head positions-with the neck flexed at right angles to the body (90°) or in extension in line with the body (180°)-during sleep in 6 cats. Polysomnography was performed twice on each cat in each of the 4 sleeping positions-P180, S180, P90, or S90. The effect of continuous positive airway pressure (CPAP) treatment was then investigated in 2 cats under the most pathogenic condition.

Setting: NA.

Patients or participants: NA.

Interventions: NA.

Measurements and results: Positions P180 and, S90 resulted, respectively, in the lowest and highest apnea-hypopnea index (AHI) (3 ± 1 vs 25 ± 2, P < 0.001), while P90 (18 ± 3, P<0.001) and S180 (13 ± 5, P<0.01) gave intermediate values. In position S90, an increase in slow wave sleep stage 1 (28% ± 3% vs 22% ± 3%, P<0.05) and a decrease in REM sleep (10% ± 2% vs 18% ± 2%, P<0.001) were also observed. CPAP resulted in a reduction in the AHI (8 ± 1 vs 27 ± 3, P<0.01), with the added benefit of sleep consolidation.

Conclusion: By mimicking human pathogenic sleep conditions, we have developed a new reversible animal model of OSA.

Keywords: animal models; body and head position; continuous positive airway pressure; obstructive sleep apnea.

Figure 1

Schematic representation of the experimental set-up. (A) Setup. The cat is restrained in the supine position. The head can be tilted forwards at 90° (i.e., S90) or extended at 180° (i.e., P180). In the circled diagram on the left, the cat is equipped with an adapted oronasal mask used to analyze respiratory airflow and apply continuous positive airway pressure (CPAP). (B) Recording conditions. This shows the results of magnetic resonance imaging performed under anesthesia in the 4 recording conditions: P180 is the prone position with the neck in extension in line with the body, S180 the supine position with the neck in extension in line with the body, S90 the supine position with the neck in flexion at 90° to the body, and P90 the prone position with the neck in flexion at 90° to the body.

Figure 2

Example of polysomnographic recording showing an obstructive apnea in the S90 position. Note the “out-of-phase” breathing movements during obstructive apnea, indicating strong respiratory effort against upper airway obstruction. Oxygen saturation (SpO₂) falls below 90% after obstructive apnea and increases slowly during a short period of normal breathing. Termination of apnea is accompanied by arousal, indicated by modifications of the EEG waveforms. The arrow indicates the direction of inspiration. EEG, electroencephalogram; EMG, electromyogram; W, wake; S1, slow wave sleep stage 1; S2, slow wave sleep stage 2; S-PGO, slow wave sleep with ponto-geniculo-occipital waves; REM, rapid eye movement sleep; Flow, bucco-nasal pressure airflow; Tho. Abdo., thoracic and abdominal movements; SpO₂, oxygen saturation.

Figure 3

Example of a 150-min hypnogram recording showing the repetition of obstructive respiratory events. The figure below the hypnogram represents 9 min of a polysomnographic recording of disrupted REM sleep. Note the succession of obstructive events accompanied by consecutive falls in oxygen saturation that interrupt REM sleep. OA, obstructive apnea; OH, obstructive hypopnea; Tls, transient lightening of sleep; EOG, electrooculogram. See Figure 2 for the abbreviations of EEG, EMG, W, S1, S2, S-PGO, REM, Flow, Tho., Abdo., and SpO₂.