Repetitive hypoxia rapidly depresses arousal from active sleep in newborn lambs

1. Arousal from sleep is an important protective mechanism that is depressed by repeated episodes of hypoxia. We aimed to determine how rapidly arousal depression occurs during repeated hypoxia and to determine if the depression is sleep state specific. 2. Three successive 12 h overnight sleep recordings were performed in six newborn lambs instrumented to record sleep state, blood pressure, heart rate and blood gases. The first (control) and third (recovery) nights were baseline studies (inspired oxygen fraction, F-I,F-O2 = 0.21) to determine the spontaneous arousal probability. During the second (test) study night, lambs were exposed to a 60 s episode of isocapnic hypoxia (F-I,F-O2 = 0.10; inspired carbon dioxide fraction, F-I,F-CO2 = 0.03) during every epoch of sleep. 3. During quiet sleep (QS), the probability of arousing to hypoxia (56%) remained significantly higher than the probability of arousing spontaneously (18%) throughout the repeated hypoxic exposures (X-2 = 81.5, P < 0.001). By contrast, during active sleep (AX) arousal rapidly became depressed with repetition of the hypoxic stimulus; the probability of arousal in hypoxia (52%) was significantly higher than the probability of spontaneous arousal (12%) during the first ten hypoxic exposures (X-2 = 18.2, P < 0.001), but there was no difference thereafter. 4. We conclude that, when repeated, moderate hypoxia very rapidly becomes ineffective as an arousing stimulus in AS, but not in QS. These results suggest that the arousal mechanism is particularly vulnerable to failure during AS.