Habituation of arousal responses after intermittent hypercapnic hypoxia in piglets

Rationale: Clinical studies have demonstrated arousal deficits in infants suffering obstructive sleep apnea, and some infant deaths have been attributed to such an arousal deficit. Objectives: To evaluate whether arousal deficits can be induced by intermittent asphyxia during normal development. Methods and Measurements: Young piglets were exposed to intermittent hypercapnic hypoxia for 4 days from age 9.55 +/- 0.5 days. Arousal responses were compared between control animals and animals exposed to intermittent hypercapnic hypoxia. Outcome measures included time to arouse after onset of the respiratory stimulus and frequency of arousals during recovery. Main Results: Arousal deficits emerged after successive exposures to hypercapnic hypoxia on Day 1, and were exacerbated con Day 4, although after overnight recovery, the deficit only became evident during the second and subsequent episode of hypercapnic hypoxia. On Day 1, time to arouse increased from 16.9 +/- 7.1 seconds in the first epoch to 41.7 +/- 28.6 seconds in the fourth epoch (p = 0.004 between cycles, one-way analysis of variance). In the recovery periods after hypercapnic hypoxia, there were 64% fewer arousals than baseline on Day 1 and 90% fewer arousals on Day 4. Respiratory effort, measured by V-T across 10 breaths before the arousal, increased from 25.7 +/- 7.6 on Day 1 to 29.1 +/- 6.8 ml/kg on Day 4 (p < 0.001, two-way analysis of variance, Day 4 vs. Day 1, respectively). Conclusions: These studies demonstrate that acute and chronic arousal deficits can be induced by intermittent asphyxia, on a background of otherwise normal postnatal development.