An endogenous circadian rhythm of respiratory control in humans

1. Many physiological and behavioural functions have circadian rhythms - en dogenous oscillations with a period of approximately 24 h that can occur ev en in the absence of sleep. We determined whether there is an endogenous ci rcadian rhythm in breathing, metabolism and ventilatory chemosensitivity in humans. 2. Ten healthy adult males were studied throughout 4 days in a stable labor atory environment. After two initial baseline days (16 h wakefulness plus 8 h sleep) that served to achieve a steady state, subjects were studied unde r constant behavioural and environmental conditions throughout 41 h of wake fulness. Ventilation, metabolism and the magnitude of the hypercapnic venti latory response (HCVR) were measured every 2 h. individuals' data were alig ned according to circadian phase (core body temperature minimum; (CBTmin) a nd averaged. 3. In the group average data, there mas a significant and large amplitude c ircadian variation in HCVR slope (average of +/- 0.41 min(-1) mmHg(-1); cor responding to +/-12.1% of 24 h mean), and a smaller amplitude rhythm in the HCVR x-asis intercept (average of +/- 1.1 mmHg +/-2.1 % of 24 h mean). 4. Despite a significant circadian variation in metabolism (+/- 3.2 % of 24 h mean), there were no detectable rhythms in tidal volume, respiratory fre quency or ventilation. This small discrepancy between metabolism and ventil ation led to a small but significant circadian variation in end-tidal P-CO2 (P-ET,(CO2); +/- 0.6 mmHg; +/-1.5% OF 24 h mean). 5. The circadian minima of the group-averaged respiratory variables occurre d 6-8 h earlier than CBTmin, suggesting that endogenous changes in CBT acro ss the circadian cycle have less of an effect on respiration than equivalen t experimentally induced changes in CBT. 6. Throughput these circadian changes, there were no correlations between H CVR parameters (slope or x-axis intercept) and either resting ventilation o r resting P-ET,P-CO2. This suggests that ventilation and P-ET,P-CO2 are lit tle influenced by central chemosensory respiratory control in awake humans even when at rest under constant environmental and behavioural conditions. 7. The characteristic change in P-ET,P-CO2 during non-rapid eye movement sl eep n as shown to be independent of circadian variations in P-ET,P-CO2, and probably reflects a change from predominantly behavioural to predominantly chemosensory respiratory control. 8. This study has documented the existence and magnitude of circadian varia tions in respiration and respiratory control in awake humans for the first time under constant behavioural and environmental conditions. These results provide unique insights into respiratory control in awake humans, and high light the importance of considering the phase of the circadian cycle in stu dies of respiratory control.