Time of day affects chemoreflex sensitivity and the carbon dioxide reserve during NREM sleep in participants with sleep apnea

Abstract

Our investigation was designed to determine whether the time of day affects the carbon dioxide reserve and chemoreflex sensitivity during non-rapid eye movement (NREM) sleep. Ten healthy men with obstructive sleep apnea completed a constant routine protocol that consisted of sleep sessions in the evening (10 PM to 1 AM), morning (6 AM to 9 AM), and afternoon (2 PM to 5 PM). Between sleep sessions, the participants were awake. During each sleep session, core body temperature, baseline levels of carbon dioxide (PET(CO2)) and minute ventilation, as well as the PET(CO2) that demarcated the apneic threshold and hypocapnic ventilatory response, were measured. The nadir of core body temperature during sleep occurred in the morning and was accompanied by reductions in minute ventilation and PetCO2 compared with the evening and afternoon (minute ventilation: 5.3 ± 0.3 vs. 6.2 ± 0.2 vs. 6.1 ± 0.2 l/min, P < 0.02; PET(CO2): 39.7 ± 0.4 vs. 41.4 ± 0.6 vs. 40.4 ± 0.6 Torr, P < 0.02). The carbon dioxide reserve was reduced, and the hypocapnic ventilatory response increased in the morning compared with the evening and afternoon (carbon dioxide reserve: 2.1 ± 0.3 vs. 3.6 ± 0.5 vs. 3.5 ± 0.3 Torr, P < 0.002; hypocapnic ventilatory response: 2.3 ± 0.3 vs. 1.6 ± 0.2 vs. 1.8 ± 0.2 l·min(-1)·mmHg(-1), P < 0.001). We conclude that time of day affects chemoreflex properties during sleep, which may contribute to increases in breathing instability in the morning compared with other periods throughout the day/night cycle in individuals with sleep apnea.

Exposure to mild intermittent hypoxia increases loop gain and the arousal threshold in participants with obstructive sleep apnoea

“…circadian rhythm) (El‐Chami et al . ) were not responsible for the sustained increase observed during the final 3 h because a similar response was not evident during the final 3 h of sleep in the control group. This latter finding is in contrast to our previous results (El‐Chami et al .…”

“…This latter finding is in contrast to our previous results (El‐Chami et al . ), which showed that chemoreflex sensitivity determined from the hypocapnic ventilatory response was greater during sleep in the evening (10.00– 13.00 h) compared to sleep in the morning (i.e. 06.00–09.00).…”

“…We believe that other factors that might influence loop gain (i.e. circadian rhythm) (El-Chami et al 2014) were not responsible for the sustained increase observed during the final 3 h because a similar response was not evident during the final 3 h of sleep in the control group. This latter finding is in contrast to our previous results (El-Chami et al 2014), which showed that chemoreflex sensitivity determined from the hypocapnic ventilatory response was greater during sleep in the evening (10.00-13.00 h) compared to sleep in the morning (i.e.…”

Time of day affects the frequency and duration of breathing events and the critical closing pressure during NREM sleep in participants with sleep apnea

“…The results from many studies indicate that the increase in chemoreflex sensitivity across the night could be the result of exposure to intermittent hypoxia, a hallmark of sleep apnea (6,14,15,19,27,53). However, we recently showed that increases in chemoreflex sensitivity and decreases in the carbon dioxide reserve were evident during sleep in the morning compared with the evening and afternoon; independent of physiological hallmarks typically associated with sleep apnea (i.e., intermittent hypoxia and sleep fragmentation) (12).…”

“…On the fifth and sixth visits, which were randomized, chemoreflex properties (i.e., chemoreflex threshold, sensitivity, and the carbon dioxide reserve) or the upper airway critical closing pressure was measured during each sleep session in 10 participants. A description of the methods used to measure the chemoreflex properties, and the results that demonstrated the effect of time of day on these properties, were published previously (12). Subsequent to this publication, 3 additional participants were enrolled, so that measures of the critical closing pressure were obtained from 13 participants.…”