A model of sleep-disordered breathing in the C57BL/6J mouse

To investigate the pathophysiological sequelae of sleep-disordered breathin g (SDB), we have developed a mouse model in which hypoxia was induced durin g periods of sleep and was removed in response to arousal or wakefulness. A n on-line sleep-wake detection system, based on the frequency and amplitude of electroencephalograph and electromyograph recordings, served to trigger intermittent hypoxia during periods of sleep. In adult male C57BL/6J mice (n = 5), the sleep-wake detection system accurately assessed wakefulness (9 7.2 +/- 1.1%), non-rapid eye movement (NREM) sleep (96.0 +/- 0.9%) and rapi d eye movement (REM) sleep (85.6 +/- 5.0%). After 5 consecutive days of SDB , 554 +/- 29 (SE) hypoxic events were recorded over a 24-h period at a rate of 63.6 +/- 2.6 events/h of sleep and with a duration of 28.2 +/- 0.7 s. T he mean nadir of fraction of inspired O-2 (FIo2) on day 5 was 13.2 +/- 0.1% , and 137.1 +/- 13.2 of the events had a nadir FIo2 < 10% O-2. Arterial blo od gases confirmed that hypoxia of this magnitude lead to a significant deg ree of hypoxemia. Furthermore, 5 days of SDB were associated with decreases in both NREM and REM sleep during the light phase compared with the 24-h p ostintervention period. We conclude that our murine model of SDB mimics the rate and magnitude of sleep-induced hypoxia, sleep fragmentation, and redu ction in total sleep time found in patients with moderate to severe SDB in the clinical setting.