Sleep apnea is a disorder whose etiology remains only partially understood. This study is primarily designed to determine the relative importance of (a) chemosensitivity and (b) neuromuscular control of upper airway patency on the development of sleep apnea. The role of ventilatory chemosensitivity in sleep apnea is particularly obscure. There is, however, some evidence that high chemosensitivity may produce an unstable ventilatory rhythm. The hyperventilation produced in response to hypoxia or hypercapnia (airway obstruction (sleep apnea) or hypoxic environment (altitude)) may yield hypocapnia and apnea with cycling ventilation. We hypothesize that reasonably high sleeping hypoxic and hypercapnic ventilatory responses may be necessary to produce apneas or periodic breathing. To test this hypothesis an individual's propensity to develop periodic breathing or apneas during NREM sleep will be measured (by currently available methods in our laboratory) and correlated with chemosensitivity. Subsequently we plan to both stimulate hypoxic sensitivity (domperidone-dopamine antagonist) and attenuate ventilatory responsiveness (dopamine) and monitor the effect on apnea production. Similar studies are planned for patients with mild to moderate obstructive sleep apnea to determine if these manipulations change the frequency of spontaneous apnea. Questions regarding the upper airway in sleep apnea also remain unanswered. Although obstructive sleep apnea patients generally have a small pharyngeal airway, the conditions that produce this reduced airway are obscure. We hypothesize that many individuals with reduced pharyngeal airway size (measured during wakefulness) do not have sleep apnea and that sleep apnea is a product, at least in part, of inadequate neuromuscular control of pharyngeal patency. Studies are planned evaluating both electromyography and pharyngeal resistance in (1) sleep apnea patients, (2) normals, and (3) individuals without sleep apnea found to have a small waking pharyngeal airway. The effect of both chemical and mechanical stimuli to the upper airway will be evaluated in all groups. Finally, the ventilatory response to added inspiratory and/or expiratory resistance during sleep has been minimally studied and is important as many otherwise healthy individuals (particularly snorers) breathe against high airflow resistance while asleep. We designed a series of studies investigating the changes in ventilation, PCO2, arterial oxygen saturation, timing, and occlusion pressure (P.1) during wakefulness and sleep in resoonse to: (1) linear inspiratory loads; (2) linear inspiratory and expiratory loads; and (3) alinear inspiratory loads (similar to physiologic upper airway resistance). This series of experiments will hopefully improve our understanding of the physiology of breathing disorders during sleep.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08HL001959-05
Application #
3082382
Study Section
Research Manpower Review Committee (MR)
Project Start
1987-07-01
Project End
1992-06-30
Budget Start
1991-07-01
Budget End
1992-06-30
Support Year
5
Fiscal Year
1991
Total Cost
Indirect Cost
Name
Pennsylvania State University
Department
Type
Schools of Medicine
DUNS #
129348186
City
Hershey
State
PA
Country
United States
Zip Code
17033
Gleeson, K (1993) Ventilatory pattern following hypoxic stimulation in nonrapid eye movement and rapid eye movement sleep. Sleep 16:S146-7
Gleeson, K; Zwillich, C W (1992) Adenosine stimulation, ventilation, and arousal from sleep. Am Rev Respir Dis 145:453-7
Robbins, M K; Gleeson, K; Zwillich, C W (1992) Effect of oxygen breathing following submaximal and maximal exercise on recovery and performance. Med Sci Sports Exerc 24:720-5
Gleeson, K; Reynolds, H Y (1992) Pneumonia in the intensive care unit setting. J Intensive Care Med 7:24-35
Gleeson, K; Zwillich, C W (1992) Adenosine infusion and periodic breathing during sleep. J Appl Physiol 72:1004-9
Leuenberger, U; Gleeson, K; Wroblewski, K et al. (1991) Norepinephrine clearance is increased during acute hypoxemia in humans. Am J Physiol 261:H1659-64
Gleeson, K; Zwillich, C W; White, D P (1990) The influence of increasing ventilatory effort on arousal from sleep. Am Rev Respir Dis 142:295-300