Repetitive hypoxia rapidly depresses cardio-respiratory responses during active sleep but not quiet sleep in the newborn lamb

Abstract

1. Arousal from sleep is an important protective response to hypoxia that becomes rapidly depressed in active sleep (AS) when hypoxia is repeated. This study questioned whether there might also be selective depression of cardio-respiratory responses to hypoxia during AS. 2. Nine newborn lambs (7-22 days of age) were studied over three successive nights. The first and third nights were baseline studies (inspired oxygen fraction, Fi,O2 = 0.21). During the second night, during every epoch of sleep, lambs were exposed to 60 s episodes of isocapnic hypoxia (Fi,O2 = 0.10). 3. During quiet sleep (QS), the probability of arousal in hypoxia exceeded the probability of spontaneous arousal (P < 0.001) throughout repeated exposures to hypoxia. Similarly, there were persisting increases in ventilation (135 +/- 25 %), blood pressure (3 +/- 1 %) and heart rate (3 +/- 1 %). 4. By contrast, rapid depression of all responses occurred during repetitive hypoxia in AS. Thus, the probability of arousal in hypoxia exceeded the probability of spontaneous arousal during the first 10 hypoxia exposures (P < 0.001) but not thereafter. Similarly, during the first 10 exposures to hypoxia, the changes in ventilation (88 +/- 15 %) and blood pressure (5 +/- 1 %) were greater than subsequent responses (P < 0.05). 5. We conclude that, when repeated, hypoxia rapidly becomes ineffective in stimulating protective arousal, ventilatory and blood pressure responses in AS, but not in QS. Selective depression of responses during AS may render the newborn particularly vulnerable to hypoxia in this state.

Figure 1. Probability of arousal from sleep and corresponding ventilatory responses during repetitive hypoxia

Probability of arousal from sleep during repetitive hypoxia (▪) during QS (A) and AS (C) plotted against the number of exposures to hypoxia (values for 11 studies in 9 lambs), compared with the probability of spontaneous arousal during normoxia (□). Associated ventilatory responses to repeated hypoxia (measured as a percentage change from normoxia levels) are shown for QS (B) and AS (D). Note that during QS the probability of arousal in response to hypoxia remained elevated above the spontaneous levels, whereas during AS the increment in arousal was abolished after just 10 exposures. * P < 0.05, probability of arousal during hypoxia vs. probability of spontaneous arousal; † P < 0.05, probability of arousal during hypoxia vs. probability of arousal during hypoxia for the first 10 hypoxic exposures. Similarly, there was no depression of the ventilatory response to hypoxia during QS, but in AS there was a depression of the ventilatory response after 10 exposures that paralleled the arousal depression. * P < 0.05, ventilatory response to hypoxia (percentage change from normoxia) vs. ventilation in normoxia; † P < 0.05, ventilatory response to hypoxia vs. ventilatory response to hypoxia for the first 10 exposures to hypoxia.

Figure 2. Respiratory and blood pressure responses to repeated hypoxia in sleep

Physiological recordings in a sleeping lamb during periods of quiet sleep (QS) and active sleep (AS) during repeated exposures to hypoxia (horizontal bar). Arousal to the waking state (W) is signified by the vertical dotted line. BP, arterial blood pressure (mmHg); P_pl, pleural pressure (arbitrary units); S_p,O2, pulse oxygen saturation (as a percentage). The hypoxia stimulus, induced by rapidly changing the air in the inspiratory line to a gas mixture of F_i,O2= 0.10, F_i,CO2= 0.03 in N₂, is denoted by the horizontal bar. Animals were exposed to a series of 40 repetitions of hypoxia during sleep; the number of each illustrated exposure in the series is indicated on each panel. During QS, progressive increases of ventilatory amplitude (P_pl) and BP occur up to the point of arousal. Note that the cardio-respiratory responses in QS are similar early (A) and late (B) in the series of exposures to hypoxia. During AS, by contrast, the progressive increases in ventilation and blood pressure that occur up to the point of arousal early in the series of exposures (C) are depressed during later exposures (D).