Journal of Applied Physiology
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J Appl Physiol (November 14, 2003). doi:10.1152/japplphysiol.00802.2003
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Submitted on July 30, 2003
Accepted on October 22, 2003

Intermittent hypoxia induces transient arousal delay in newborn mice

Estelle Durand1, Frederic Lofaso2, Stephane Dauger3, Guy Vardon4, Claude Gaultier5, and Jorge Gallego1*

1 E9935, INSERM, Paris, France
2 Service de Physiologie-Explorations Fonctionnelles, Hopital Raymond-Poincare, Garches, France
3 E9935, INSERM, Paris, France; Service de Pediatrie-Reanimation, Hopital Robert-Debre, Paris, France
4 URAPC, Universite de Picardie, Amiens, France
5 E9935, INSERM, Paris, France; Service de Physiologie, Hopital Robert-Debre, Paris, France

* To whom correspondence should be addressed. E-mail: gallego{at}idf.inserm.fr.

Previous studies suggested that defective arousal might be a major mechanism in sleep-disordered breathing such as sudden infant death syndrome (SIDS) and obstructive sleep apnea (OSA). In this study, we examined the effects of intermittent hypoxia (IH) on the arousal response to hypoxia in 4-day old mice. We hypothesized that IH would increase arousal latency, as previously reported in other species, and we measured the concomitant changes in ventilation to shed light on the relationship between breathing and arousal. Arousal was scored using behavioral criteria. Breathing variables were measured noninvasively using whole-body flow plethysmography. In the hypoxic group (n=14), the pups were exposed to 5% O2 in N2 for 3 minutes and returned to air for 6 minutes. This test was repeated 8 times. The normoxic mice (n=14) were constantly exposed to normoxia. The hypoxic mice showed a 60% increase in arousal latency (P<0.0001). Normoxic controls showed virtually no arousals. IH depressed normoxic ventilation below baseline pre-hypoxic levels, while preserving the ventilatory response to hypoxia. The breathing pattern and arousal responses recovered fully after 2 hours of normoxia. We conclude that IH rapidly and reversibly depressed breathing and delayed arousal in newborn mice. Both effects may be due to hypoxia-induced release of inhibitory neurotransmitters acting concomitantly on both functions.




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