This proposal tests the hypothesis that both irregular and periodic breathing can result from interactions between stochastic disturbances to respiration (i.e., disturbances that are random relative to the respiratory cycle) and the nonlinear deterministic properties of respiratory neurochemical and neuromechanical feedback systems. Such disturbances may originate within the respiratory system (e.g., in receptor or neuronal discharges, in blood gas fluctuations) or external to it (e.g., from higher brain activities). Preliminary experimental and mathematical modelling studies demonstrate that under various normal and pathological conditions """"""""noisy"""""""" breath to breath disturbances to respiratory pattern, ventilation, or blood gases can excite additional modes of respiratory behavior, including self-sustaining breath to breath variations in respiratory cycle parameters, irregular apneas, and periodic oscillations in ventilation. Proposed studies will examine first the effects of chemical drive and sleep state on the characteristics of spontaneous disturbances to, and the resulting breath to breath variations in, ventilatory parameters and respiratory EMGs in human subjects. The influence of these disturbances on the occurrence of periodic breathing and apneas will be predicted through mathematical simulations and tested experimentally. Coordinated studies involving awake and asleep humans and anesthetized rats will assess the roles of several physiological mechanisms, including central and peripheral chemoreceptors and pulmonary mechanoreceptors, in promoting oscillations and self-sustaining variations in tidal volume, breath timing, and ventilation. Contributions of these mechanisms will be assessed by first reducing, then enhancing, the physiological activity of each mechanism. These studies will utilize new techniques for optimal control of blood gases in humans and for white-noise identification of feedback system properties. Applicability of the findings to patient populations will be explored using mathematical simulations. These studies will evaluate a new framework for understanding the causes of irregular and periodic breathing, which may be important for developing early therapeutic interventions in patients, and will develop new sensitive techniques for assessing ventilatory stability.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL044889-05
Application #
2221732
Study Section
Respiratory and Applied Physiology Study Section (RAP)
Project Start
1991-04-01
Project End
1996-03-31
Budget Start
1994-04-01
Budget End
1996-03-31
Support Year
5
Fiscal Year
1994
Total Cost
Indirect Cost
Name
University of Kentucky
Department
Miscellaneous
Type
Other Domestic Higher Education
DUNS #
832127323
City
Lexington
State
KY
Country
United States
Zip Code
40506
Lai, J; Bruce, E N (1997) Ventilatory stability to transient CO2 disturbances in hyperoxia and normoxia in awake humans. J Appl Physiol 83:466-76
Bruce, E N (1996) Accessing chemosensitivity and ventilatory stability from transient stimuli. Sleep 19:S157-9
Bruce, E N (1996) Temporal variations in the pattern of breathing. J Appl Physiol 80:1079-87
Bruce, E N (1996) Deflation-related variability of breathing pattern persists with intact upper airway. Respir Physiol 106:273-83
Modarreszadeh, M; Bruce, E N; Hamilton, H et al. (1995) Ventilatory stability to CO2 disturbances in wakefulness and quiet sleep. J Appl Physiol 79:1071-81
Dhawale, P; Bruce, E N (1995) Estimation of hypoxic ventilatory dynamics using pseudorandom inputs. Respir Physiol 101:267-78
Modarreszadeh, M; Bruce, E N (1994) Ventilatory variability induced by spontaneous variations of PaCO2 in humans. J Appl Physiol 76:2765-75
Sammon, M (1994) Geometry of respiratory phase switching. J Appl Physiol 77:2468-80
Sammon, M (1994) Symmetry, bifurcations, and chaos in a distributed respiratory control system. J Appl Physiol 77:2481-95
Sammon, M; Romaniuk, J R; Bruce, E N (1993) Bifurcations of the respiratory pattern produced with phasic vagal stimulation in the rat. J Appl Physiol 75:912-26

Showing the most recent 10 out of 14 publications