Physiological and genomic consequences of intermittent hypoxia - Selected Contribution: Regulation of sleep-wake states in response to intermittent hypoxic stimuli applied only in sleep

Recurrent sleep-related hypoxia occurs in common disorders such as obstruct ive sleep apnea (OSA). The marked changes in sleep after treatment suggest that stimuli associated with OSA (e.g., intermittent hypoxia) may significa ntly modulate sleep regulation. However, no studies have investigated the i ndependent effects of intermittent sleep-related hypoxia on sleep regulatio n and recovery sleep after removal of intermittent hypoxia. Ten rats were i mplanted with telemetry units to record the electroencephalogram (EEG), nec k electromyogram, and body temperature. After >7 days recovery, a computer algorithm detected sleep-wake states and triggered hypoxic stimuli (10% O-2 ) or room air stimuli only during sleep for a 3-h period. Sleep-wake states were also recorded for a 3-h recovery period after the stimuli. Each rat r eceived an average of 69.0 +/- 6.9 hypoxic stimuli during sleep. The non-ra pid eye movement (non-REM) and rapid-eye-movement (REM) sleep episodes aver aged 50.1 +/- 3.2 and 58.9 +/- 6.6 s, respectively, with the hypoxic stimul i, with 32.3 +/- 3.2 and 58.6 +/- 4.8 s of these periods being spent in hyp oxia. Compared with results for room air controls, hypoxic stimuli led to i ncreased wakefulness (P< 0.005), nonsignificant changes in non-REM sleep, a nd reduced REM sleep (P< 0.001). With hypoxic stimuli, wakefulness episodes were longer and more frequent, non-REM periods were shorter and more frequ ent, and REM episodes were shorter and less frequent (P< 0.015). Hypoxic st imuli also increased faster frequencies in the EEG (P< 0.005). These effect s of hypoxic stimuli were reversed on return to room air. There was a rebou nd increase in REM sleep, increased slower non-REM EEG frequencies, and dec reased wakefulness (P< 0.001). The results show that sleep-specific hypoxia leads to significant modulation of sleep-wake regulation both during and a fter application of the intermittent hypoxic stimuli. This study is the fir st to determine the independent effects of sleep-related hypoxia on sleep r egulation that approximates OSA before and after treatment.