The purpose of this application for a Research Career Development Award is to permit the Principal Investigator (PI) to devote a substantially greater portion of his time for research into the effects of sleep on the control of breathing. During the tenure of this proposes project, the PI will combine mathematical modeling and parameter estimation methodology with experiments on humans to obtain a better understanding of the dynamic mechanisms that lead to respiratory variability and recurrent apnea during sleep. The RCDA will free up sufficient time for him to conduct the proposed studies, as well as to obtain a firm grounding in the clinical and neurophysiological aspects of sleep through reading, increased interactions with experts in the field, and participation in colloquiums. The experience and training obtained through such an opportunity would be invaluable for his current and future development as in independent investigator in sleep physiology, particularly as it pertains to respiratory control. At the same time, the PI will be able to explore the applicability of new approaches derived from nonlinear dynamics, chaos theory and neural networks. The presence within the University of several experts in these new areas, as well as in the neurosciences, provides an ideal environment for the academic growth of the PI. The inclusion of two clinical colleagues, one in pulmonary medicine and the other in sleep disorders, as Co-Investigators in this project will significantly improve the PI's appreciation of the pathophysiological aspects of sleep. In the proposed project, experiments will be performed on both healthy subjects and patients with sleep apnea syndrome to determine the relative importance of chemoresponsiveness, sensitivity of arterial blood gas tensions to ventilatory changes (plant gain), respiratory phase-switching, sleep state changes and upper airway mechanics in mediating sleep-related breathing disorders. Simple noninvasive procedures combined with specially designed computational algorithms will be permit the tracking of chemoresponsiveness, plant gain, and arterial blood gases during sleep. Application of modeling also allows the estimation of the time-course for the 'wakefulness stimulus'. Analysis of the temporal relationships between these factors and changes in upper airway resistance will be used to extend an existing model of the interaction between sleep state and respiratory control.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Modified Research Career Development Award (K04)
Project #
5K04HL002536-02
Application #
3074510
Study Section
Metabolic Pathology Study Section (MEP)
Project Start
1990-09-01
Project End
1995-08-31
Budget Start
1991-09-01
Budget End
1992-08-31
Support Year
2
Fiscal Year
1991
Total Cost
Indirect Cost
Name
University of Southern California
Department
Type
Schools of Engineering
DUNS #
041544081
City
Los Angeles
State
CA
Country
United States
Zip Code
90089
Khoo, M C; Shin, J J; Asyali, M H et al. (1998) Ventilatory dynamics of transient arousal in patients with obstructive sleep apnea. Respir Physiol 112:291-303
Shin, J J; Berry, R B; Khoo, M C (1998) Fuzzy assessment of sleep-disordered breathing during continuous positive airway pressure therapy. Sleep 21:817-28
Kim, T S; Khoo, M C (1997) Estimation of cardiorespiratory transfer under spontaneous breathing conditions: a theoretical study. Am J Physiol 273:H1012-23
Khoo, M C; Koh, S S; Shin, J J et al. (1996) Ventilatory dynamics during transient arousal from NREM sleep: implications for respiratory control stability. J Appl Physiol 80:1475-84
Tallman Jr, R D; Ghazanshahi, S D; Khoo, M C (1996) Transduction dynamics of intrapulmonary CO2 receptors. Respir Physiol 106:115-25
Khoo, M C; Berry, R B (1996) Modeling the interaction between arousal and chemical drive in sleep-disordered breathing. Sleep 19:S167-9
Khoo, M C; Anholm, J D; Ko, S W et al. (1996) Dynamics of periodic breathing and arousal during sleep at extreme altitude. Respir Physiol 103:33-43
Pianosi, P; Khoo, M C (1995) Change in the peripheral CO2 chemoreflex from rest to exercise. Eur J Appl Physiol Occup Physiol 70:360-6
Khoo, M C; Yang, F; Shin, J J et al. (1995) Estimation of dynamic chemoresponsiveness in wakefulness and non-rapid-eye-movement sleep. J Appl Physiol 78:1052-64
Yang, F; Khoo, M C (1994) Ventilatory response to randomly modulated hypercapnia and hypoxia in humans. J Appl Physiol 76:2216-23

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