We propose further study of the regulation of breathing in various physiologic states in unanesthetized humans and dogs with specific emphasis on the underlying mechanisms and the mechanical consequences. To this end, the goals and procedures of this proposed research are as follows: 1. To determine the limits of the healthy pulmonary control system for gas transport, for respiratory muscle pressure development and for ventilatory output at extraordinarily elevated levels of metabolic demand. We hypothesize that limitations to function in the pulmonary control system will be manifested and will present significant limitations to maximum oxygen consumption, as the level of cardio-vascular and locomotor muscle fitness is increased in young (20-30 yrs) and elderly (55-75 yrs) highly endurance trained athletes, in the elite asthmatic athlete and in the racing greyhound. Special emphasis will be focused on alveolar to arterial gas exchange and on the mechanical constraints imposed by the chest wall on alveolar hyperventilation in heavy exercise. 2. To determine the effects of various types of acute and chronic ventilatory stimuli and inhibitors on respiratory muscle recruitment, on respiratory muscle length and on the timing of neuro-mechanical coupling throughout the breath. Physiologic states to be studied include acute and chronic chemoreceptor stimulation, locomotion and internal mechanical loading and unloading. These studies will also address the feed-forward and feed-back mechanisms responsible for these patterns of recruitment and the mechanical consequences of this recruitment to lung and chest wall function. 3. To quantitate the effects of sleep-induced increases in airway resistance on CO2 retention and respiratory muscle recruitment. Two closely related effects of sleep state will also be studied: a) the selective responses of inspiratory, expiratory abdominal and rib cage and upper airway """"""""respiratory"""""""" muscles to inhibition secondary to small reductions in PaCO2 and to mechanical """"""""unloading"""""""" in sleep; and b) the role of carotid chemoreceptors in the mediation of hypocapnic inhibition during all sleep stages.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37HL015469-22
Application #
2214873
Study Section
Special Emphasis Panel (NSS)
Project Start
1977-09-01
Project End
1997-08-31
Budget Start
1994-09-01
Budget End
1995-08-31
Support Year
22
Fiscal Year
1994
Total Cost
Indirect Cost
Name
University of Wisconsin Madison
Department
Public Health & Prev Medicine
Type
Schools of Medicine
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715
Smith, Curtis A; Blain, Grégory M; Henderson, Kathleen S et al. (2015) Peripheral chemoreceptors determine the respiratory sensitivity of central chemoreceptors to CO2 : role of carotid body CO2. J Physiol 593:4225-43
Dempsey, Jerome A; Xie, Ailiang; Patz, David S et al. (2014) Physiology in medicine: obstructive sleep apnea pathogenesis and treatment--considerations beyond airway anatomy. J Appl Physiol (1985) 116:3-12
Dempsey, Jerome A; Smith, Curtis A (2014) Pathophysiology of human ventilatory control. Eur Respir J 44:495-512
Xie, Ailiang; Teodorescu, Mihaela; Pegelow, David F et al. (2013) Effects of stabilizing or increasing respiratory motor outputs on obstructive sleep apnea. J Appl Physiol (1985) 115:22-33
Amann, Markus; Blain, Gregory M; Proctor, Lester T et al. (2011) Implications of group III and IV muscle afferents for high-intensity endurance exercise performance in humans. J Physiol 589:5299-309
Lovering, Andrew T; Elliott, Jonathan E; Beasley, Kara M et al. (2010) Pulmonary pathways and mechanisms regulating transpulmonary shunting into the general circulation: an update. Injury 41 Suppl 2:S16-23
Dempsey, Jerome A; Veasey, Sigrid C; Morgan, Barbara J et al. (2010) Pathophysiology of sleep apnea. Physiol Rev 90:47-112
Smith, Curtis A; Forster, Hubert V; Blain, Gregory M et al. (2010) An interdependent model of central/peripheral chemoreception: evidence and implications for ventilatory control. Respir Physiol Neurobiol 173:288-97
Forster, H V; Smith, C A (2010) Contributions of central and peripheral chemoreceptors to the ventilatory response to CO2/H+. J Appl Physiol 108:989-94
Lovering, Andrew T; Haverkamp, Hans C; Romer, Lee M et al. (2009) Transpulmonary passage of 99mTc macroaggregated albumin in healthy humans at rest and during maximal exercise. J Appl Physiol (1985) 106:1986-92

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