CIRCADIAN AND WAKE-DEPENDENT ASPECTS OF RESPIRATION

Project: Research project

Project Details

Description

When humans fall asleep there are changes in breathing, in the feedback system that regulates arterial blood gases, and in the degree of bronchoconstriction. These changes have serious clinical consequences in the common disorders of obstructive sleep apnea, chronic obstructive lung disease, and asthma. Our preliminary data provides evidence that such changes during sleep may cause, or interact with, changes in respiratory control related to the effects of circadian rhythms or the accumulation of a sleep debt. This research will test the hypotheses that respiratory control mechanisms are significantly affected by the phase of the endogenous circadian cycle (caused for instance, by changes in circulating hormone levels or direct effects from the endogenous circadian pacemaker) and by sleep loss (for instance, via the build-up of a sleep promoting substance). To uncover the underlying circadian and wake-dependent aspects of respiration in the absence of sleep, an established constant routine protocol will minimize the effects of environmental and behavioral stimuli on breathing (such as sleep, large meals, movement, noise and light). Measurements will include end-tidal CO2 level, ventilation, ventilatory responses to hypercapnia and hypoxia, and indices of pulmonary function. Underlying physiological mechanisms will be inferred by comparing phase angles of the respiratory variables with those of other known circadian rhythms (e.g., core body temperature). Wake-dependent and circadian effects and their interaction will be distinguished statistically. To further determine underlying mechanisms, the pure wake-dependent and circadian influences on arterial blood gases will be measured in a second constant routine study in patients with congenital central hypoventilation syndrome (CCHS) who have a lesion in a common peripheral and central chemoreceptor pathway. It is hypothesized that circadian and wake- dependent influences on breathing will be greater in CCHS patients because the effects on breathing of hormones, temperature, etc., are unfettered by the negative feedback control of arterial blood gases. Quantification of circadian and wake-dependent effects on breathing will substantially improve our interpretation of experimental and clinical data in patients with breathing, sleep or circadian disorders. This work will establish the importance of considering the phase of the circadian cycle and the extent of disruption of sleep in experimental design, and the management and assessment of respiratory patients.
StatusFinished
Effective start/end date6/5/9811/30/02

Funding

  • National Institutes of Health
  • National Institutes of Health: $203,848.00
  • National Institutes of Health: $223,347.00

ASJC

  • Medicine(all)

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