title: Neuromechanical control of the isolated upper airway of mice.
abstract: We characterized the passive structural and active neuromuscular control of pharyngeal collapsibility in mice and hypothesized that pharyngeal collapsibility, which is elevated by anatomic loads, is reduced by active neuromuscular responses to airflow obstruction. To address this hypothesis, we examined the dynamic control of upper airway function in the isolated upper airway of anesthetized C57BL/6J mice. Pressures were lowered downstream and upstream to the upper airway to induce inspiratory airflow limitation and critical closure of the upper airway, respectively. After hyperventilating the mice to central apnea, we demonstrated a critical closing pressure (Pcrit) of -6.2 +/- 1.1 cmH(2)O under passive conditions that was unaltered by the state of lung inflation. After a period of central apnea, lower airway occlusion led to progressive increases in phasic genioglossal electromyographic activity (EMG(GG)), and in maximal inspiratory airflow (Vi(max)) through the isolated upper airway, particularly as the nasal pressure was lowered toward the passive Pcrit level. Moreover, the active Pcrit fell during inspiration by 8.2 +/- 1.4 cmH(2)O relative to the passive condition (P < 0.0005). We conclude that upper airway collapsibility (passive Pcrit) in the C57BL/6J mouse is similar to that in the anesthetized canine, feline, and sleeping human upper airway, and that collapsibility falls markedly under active conditions. Active EMG(GG) and Vi(max) responses dissociated at higher upstream pressure levels, suggesting a decrease in the mechanical efficiency of upper airway dilators. Our findings in mice imply that anatomic and neuromuscular factors interact dynamically to modulate upper airway function, and provide a novel approach to modeling the impact of genetic and environmental factors in inbred murine strains.
authors.affiliation: Johns Hopkins Sleep Disorders Center, 5501 Hopkins Bayview Circle, Baltimore, MD 21224, USA.
authors.forename: Audrey
authors.initials: A
authors.lastname: Liu
authors.forename: Luis
authors.initials: L
authors.lastname: Pichard
authors.forename: Hartmut
authors.initials: H
authors.lastname: Schneider
authors.forename: Susheel P
authors.initials: SP
authors.lastname: Patil
authors.forename: Philip L
authors.initials: PL
authors.lastname: Smith
authors.forename: Vsevolod
authors.initials: V
authors.lastname: Polotsky
authors.forename: Alan R
authors.initials: AR
authors.lastname: Schwartz
mesh_terms: D000402:Airway Obstruction / Q000503:physiopathology; D000818:Animals; D001049:Apnea / Q000503:physiopathology*; D003187:Compliance; D004576:Electromyography; D006985:Hyperventilation / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009130:Muscle, Smooth / Q000294:innervation*; D009469:Neuromuscular Junction / Q000503:physiopathology*; D010614:Pharynx / Q000294:innervation*; D011175:Positive-Pressure Respiration; D011312:Pressure; D012119:Respiration; D020181:Sleep Apnea, Obstructive / Q000503:physiopathology; D013997:Time Factors; D014132:Trachea / Q000294:innervation