Adenosine Stimulation, Ventilation, and Arousal from Sleep

Abstract

The mechanism for arousal from sleep resulting from respiratory stimuli is unclear. We hypothesized that arousal is a result of increasing ventilation during sleep. To determine if this is true we compared minute ventilation at the point of arousal from non-REM sleep produced by the respiratory stimulant adenosine to that resulting from progressive hypercapnic stimulation. If this hypothesis is correct, the quantity of breathing immediately preceding arousal from sleep should be similar for each stimulus. We monitored electroencephalogram (EEG), electromyogram (EMG), end-tidal CO2, and inspired minute ventilation (VI) in five healthy young men during full-night sleep studies. Sleep state was monitored during the baseline state, during an intravenous infusion of 80 micrograms/kg/min of adenosine, and during multiple trials of progressive hyperoxic hypercapnia. Arousal from sleep occurred in association with increased breathing 4.2 +/- 1.1 times during adenosine infusion, 2.0 +/- 0 times during hypercapnic stimulation, and 4.0 +/- 0.6 times in the absence of stimulated breathing (spontaneously) per subject. Minute ventilation for the breath preceding arousal associated with adenosine stimulation (13.0 +/- 1.4 L/min) was similar to that preceding arousal caused by hypercapnia (12.9 +/- 1.1 L/min). In each case this level of breathing was greater than that preceding spontaneously occurring arousals (8.2 +/- 1.1 L/min), p less than 0.05). Although variable between subjects, there was a high correlation for these two variables within subjects (R = 0.96, p = 0.01). These data support the hypothesis that increasing ventilation induces arousal from sleep when ventilation is increased regardless of the stimulus producing this rising drive to breathe.