NEW ANIMAL MODEL OF OSA AND RESPONSE TO CPAP
A New Animal Model of Obstructive Sleep Apnea Responding to Continuous Positive Airway Pressure
Pierre-Charles Neuzeret, PhD1,2,3; Frédéric Gormand, PhD, MD1,2,3; Philippe Reix, PhD, MD1,2,3; Sandrine Parrot, PhD2,3,4; Jean-Pierre Sastre, PhD1,2,3; Colette Buda, BSc1,2,3; Gérard Guidon, BSc1,2,3; Kazuya Sakai, PhD1,2,3; Jian-Sheng Lin, PhD, MD1,2,3
1INSERM, U1028; CNRS, UMR5292; Lyon Neuroscience Research Center, Integrated Physiology of Brain Arousal Systems, Lyon, F-69000, France
; 2University Lyon, F-69000, France
; 3University Lyon 1, Villeurbanne, F-69000, France
; 4INSERM, U1028; CNRS, UMR5292; Lyon Neuroscience Research Center, NeuroChem, Lyon, F-69000, France
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.
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.
Patients or Participants:
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.
By mimicking human pathogenic sleep conditions, we have developed a new reversible animal model of OSA.
Neuzeret PC; Gormand F; Reix P; Parrot S; Sastre JP; Buda C; Guidon G; Sakai K; Lin JS. A new animal model of obstructive sleep apnea responding to continuous positive airway pressure. SLEEP 2011;34(4):541-548.