Ventilatory and arousal responses to hypoxia and hypercapnia in a canine model of obstructive sleep apnea

• Published in: American journal of respiratory and critical care medicine 1997-09, Vol.156 (3), p.886-894
• Main Authors: KIMOFF, R. J, BROOKS, D, HORNER, R. L, KOZAR, L. F, RENDER-TEIXEIRA, C. L, CHAMPAGNE, V, MAYER, P, PHILLIPSON, E. A
• Format: Article
• Language: English
• Subjects: Animals; Arousal - physiology; Biological and medical sciences; Blood Gas Analysis; Disease Models, Animal; Dogs; Feasibility Studies; Hypercapnia - complications; Hypercapnia - physiopathology; Hypoxia - complications; Hypoxia - physiopathology; Investigative techniques of respiratory function; Investigative techniques, diagnostic techniques (general aspects); Medical sciences; Polysomnography; Sleep Apnea Syndromes - complications; Sleep Apnea Syndromes - physiopathology; Sleep Stages - physiology; Tidal Volume - physiology; Time Factors; Wakefulness - physiology
• ISSN: 1073-449X; 1535-4970
• DOI: 10.1164/ajrccm.156.3.9610060

We have previously described a canine model of obstructive sleep apnea (OSA) in which sleep-wake state is monitored continuously by a computer that produces tracheal occlusion when sleep occurs. Our aim was to assess the effects of long-term application of this model on resting ventilation and on the ventilatory and arousal responses to hypercapnia and hypoxia. Five dogs were maintained on the model for 15.5 +/- 1.7 (mean +/- SE) wk, with a mean apnea index of 57.5 +/- 4.5 occlusions/h of sleep. Resting ventilation and the ventilatory and arousal responses to progressive hypoxic and hypercapnic rebreathing were assessed during wakefulness (W) and both slow-wave (SWS) and rapid-eye-movement (REM) sleep at baseline prior to intervention, at the end of the OSA phase, and following a 1 to 3-mo recovery period. During the period of OSA there were small changes in respiratory timing at rest, but no significant changes in PCO2 or SaO2. As compared with baseline, the ventilatory response to hypoxia during OSA was strikingly reduced during W, and significantly although less markedly reduced during SWS and REM. The reduction was due to a decreased breathing frequency response to hypoxia. In addition, during OSA there was a significant decrease from baseline in SaO2 at arousal during hypoxic rebreathing in both SWS and REM. All responses returned to normal during recovery. In contrast to hypoxia, hypercapnic ventilatory responses during OSA were slightly increased over their baseline values both in W and SWS, owing to a leftward shift of the ventilation-versus-PCO2 relationship. During recovery, these responses reverted partly to baseline for W and reverted completely to baseline for SWS. There were no significant changes in arousal PCO2 during hypercapnic rebreathing in either SWS or REM across the pre-OSA baseline, OSA, and post-OSA recovery periods. We conclude that long-term application of the OSA model is associated with a selective, reversible decrease in ventilatory and arousal responses to hypoxia.