Published ahead of print on September 25, 2003, doi:10.1164/rccm.200304-462OC Am. J. Respir. Crit. Care Med., Volume 168, Number 12, December 2003, 1520-1527 A more recent version of this article appeared on December 15, 2003
Submitted on April 2, 2003 Differences in sleep-induced hypoxia between A/J and DBA/2J mouse strainsArnon E Rubin1,1 Medicine, The Johns Hopkins Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA, 2 Environmental Health Sciences, The Johns Hopkins Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA * To whom correspondence should be addressed. E-mail: codonne1{at}jhmi.edu.
In Obstructive sleep apnea (OSA), hypoxic ventilatory sensitivity may affect the degree of hypoxic stress and sleep disruption that occur in response to upper airway obstruction. We induced (a) sleep-induced hypoxia (SIH) or (b) sleep fragmentation without hypoxia (SF) for five days (12 hrs:12 hrs light/dark cycle) in two inbred mouse strains with low (A/J) and high (DBA/2J) hypoxic ventilatory sensitivities. During SIH, the time to arousal (26.4±1.1 vs. 21.3±1.5sec, P<0.025) and the severity of hypoxic exposure (nadir FiO2: 11.5±0.4 vs.13.6±0.1%, P<0.002) was greater in A/J than DBA/2J mice. Furthermore, A/J mice had a greater frequency of hypoxic events (640±29 vs. 368±33events/24hr, P<0.001) and total sleep time (47.5±2.8 vs. 26.5±2.4%/24hr, P<0.0001) during SIH than DBA/2J mice. In contrast, the event characteristics and total sleep time during SF were the same in both strains. Furthermore, in the light phase, both strains showed a longer (P<0.01) time to arousal during SIH and SF compared to the dark phase. We conclude that genetic background can influence respiratory events and sleep architecture during SIH, and that the arousal threshold is subject to circadian variation. Our data imply that individuals with low hypoxic sensitivity may be at a greater risk for hypoxia-related complications of OSA. Key words: carotid body, genetics, hypoxic ventilatory response, obstructive sleep apnea, sleep fragmentation
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