The purpose of this proposal is to examine the mechanical, neuromuscular, and reflex control of airflow in the upper airway in both humans during sleep and in an isolated canine upper airway. The major focus of this work is to elucidate underlying mechanisms in the control upper airway airflow and to determine whether specific alterations exist in the control of airflow in patients with obstructive sleep apnea. Specifically, a Starling resistor model of the upper airway will be employed to examine the regulation of airflow and its mechanical determinants: pharyngeal critical pressure (Pcrit) and upstream nasal resistance (RN).
In Specific Aim #1, the influence of alterations in upper airway structure on airflow and its mechanical determinants in (a) the presence and absence of upper airway muscle activation, and (b) after surgical reconstruction of the upper airway will be examined.
In Specific Aim #2, the effect of phasic neuromuscular activation of the upper airway on flow and its mechanical determinants will be determined.
In Specific Aim #3, the effect of alterations in reflex control will be determined by examining the chemical and mechanical reflex control of upper airway neuromuscular activity, airflow, and its mechanical determinants. In each specific aim, experiments in the isolated canine upper airway will examine each of the factors outlined above to elucidate basic mechanisms controlling the mechanical, phasic neuromuscular activation, and reflex control of the upper airway. These animal experiments are designed to test present concepts believed important in the regulation of airflow in the upper airway, and to facilitate the development and application of new approaches to treating patients with obstructive sleep apnea. Specialized recording techniques for sleep, pressure, flow, and EMG activity will be employed and their relationships to the mechanical determinants of flow will be determined.
| Wei, Tony; Erlacher, Markus A; Grossman, Peter et al. (2013) Approach for streamlining measurement of complex physiological phenotypes of upper airway collapsibility. Comput Biol Med 43:600-6 |
| Hernandez, A B; Kirkness, J P; Smith, P L et al. (2012) Novel whole body plethysmography system for the continuous characterization of sleep and breathing in a mouse. J Appl Physiol 112:671-80 |
| Polotsky, Mikhael; Elsayed-Ahmed, Ahmed S; Pichard, Luis et al. (2012) Effects of leptin and obesity on the upper airway function. J Appl Physiol 112:1637-43 |
| Chin, Chien-Hung; Kirkness, Jason P; Patil, Susheel P et al. (2012) Compensatory responses to upper airway obstruction in obese apneic men and women. J Appl Physiol (1985) 112:403-10 |
| Kirkness, J P; McGinley, B M; Sgambati, F P et al. (2011) Developing quantitative physiological phenotypes of sleep apnea for epidemiological studies. Conf Proc IEEE Eng Med Biol Soc 2011:8319-22 |
| Polotsky, Mikhael; Elsayed-Ahmed, Ahmed S; Pichard, Luis et al. (2011) Effect of age and weight on upper airway function in a mouse model. J Appl Physiol 111:696-703 |
| Kirkness, Jason P; Peterson, Leigh A; Squier, Samuel B et al. (2011) Performance characteristics of upper airway critical collapsing pressure measurements during sleep. Sleep 34:459-67 |
| Hoshino, Yuko; Ayuse, Takao; Kobayashi, Masato et al. (2011) The effects of hormonal status on upper airway patency in normal female subjects during propofol anesthesia. J Clin Anesth 23:527-33 |
| Schwartz, Alan R; Schneider, Hartmut; Smith, Philip L et al. (2011) Physiologic phenotypes of sleep apnea pathogenesis. Am J Respir Crit Care Med 184:1105-6 |
| Kirkness, J P; Verma, M; McGinley, B M et al. (2011) Pitot-tube flowmeter for quantification of airflow during sleep. Physiol Meas 32:223-37 |
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