The ventilatory response to arousal from sleep is not fully explained by differences in CO2 levels between sleep and wakefulness

Arousal from sleep is associated with transient stimulation of ventilation above normal waking levels that predisposes to subsequent breathing instability and central apnoea. The transient hyperpnoea at arousal is normally explained by differences in arterial partial pressure of CO2 (Pa,CO2) between sleep and wakefulness, with a higher Pa,CO2 in sleep leading to stimulation of ventilation at arousal according to the awake ventilatory response to CO2. Surprisingly, however, the validity of this current model in fully explaining the increased ventilation at arousal from sleep has not been directly tested.This study tests the hypothesis that the level of ventilation at arousal from non-rapid eye movement (non-REM) sleep is greater than that produced by elevating Pa,CO2 in wakefulness to the sleeping level, i.e. the ventilation predicted by the current model.Studies were performed in five dogs. Inspired CO2 was used to increase end-tidal partial pressure of CO2 (PET,CO2) in wakefulness and measure the ventilatory response. The same PET,CO2 was then maintained in non-REM sleep. Ventilation was measured for 10 breaths before and after arousal from non-REM sleep induced by a 72 dB tone.Arousal from sleep produced a transient surge in ventilation of 1.42 ± 0.35 l min−1 (P= 0.005). This increased ventilation was due to arousal from sleep per se as the tone alone produced no change in awake ventilation. In support of the hypothesis, ventilation at wake onset from sleep was greater by 0.83 ± 0.28 l min−1 (P= 0.031) than the ventilation elicited in wakefulness by raising PET,CO2 to the sleeping level.The results show that > 50% of the increase in ventilation at wake onset from sleep is not attributable to the awake ventilatory response to the elevated Pa,CO2 that was previously present in sleep. This result leads to important modifications of the physiological model currently used to explain the ventilatory consequences of arousal from sleep