The long-term objective of this proposal is to test the hypothesis that the muscles that protrude and retract the tongue (genioglossus and hypoglossus/styloglossus muscles, respectively) are co-activated during inspiration, and that co-contraction contributes significantly to the maintenance of pharyngeal airway patency. The conceptual model is that co-contraction during inspiration stiffens the tongue as the antagonist muscles work against one another, thereby minimizing backward displacement of the tongue and subsequent occlusion of the pharynx. Significant new data showing respiratory-related co-activation of the protrudor and retractor muscles in animal models, as well as recent evidence showing improved inspiratory airflow with co-activation in human subjects with obstructive sleep apnea, provide strong support for this conceptual framework. Accordingly, the following Specific Aims are designed to rigorously test the co-activation hypothesis using an anesthetized rat model:
Aim 1 is to demonstrate that the protrudor and retractor muscles of the tongue are co-activated during breathing and that they respond similarly to changes in respiratory related stimuli.
Aim 2 is to show that co-activation of the extrinsic tongue muscles will improve pharyngeal airway mechanics more than the independent activation of either the protrudor or retractor muscles.
Aim 3 is to demonstrate that the initial operating length of the tongue muscles will influence: a) the magnitude of respiratory related tongue movements, b) the ability of the tongue muscles to modulate pharyngeal airway flow mechanics, c) the fatigability of the tongue muscles. These experiments will lay the foundation for new and improved treatment strategies for persons with obstructive sleep apnea or with other conditions that are caused by malfunction of the tongue motor system.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL056876-03
Application #
6183764
Study Section
Respiratory and Applied Physiology Study Section (RAP)
Project Start
1998-04-10
Project End
2003-03-31
Budget Start
2000-04-01
Budget End
2001-03-31
Support Year
3
Fiscal Year
2000
Total Cost
$190,963
Indirect Cost
Name
University of Arizona
Department
Physiology
Type
Schools of Medicine
DUNS #
City
Tucson
State
AZ
Country
United States
Zip Code
85721
Patel-Khurana, Nilam; Fregosi, Ralph F (2015) Motor unit number in a small facial muscle, dilator naris. Exp Brain Res 233:2897-902
Pilarski, Jason Q; Fregosi, Ralph F (2009) Prenatal nicotine exposure alters medullary nicotinic and AMPA-mediated control of respiratory frequency in vitro. Respir Physiol Neurobiol 169:1-10
Schmitt, Kori; DelloRusso, Christiana; Fregosi, Ralph F (2009) Force-EMG changes during sustained contractions of a human upper airway muscle. J Neurophysiol 101:558-68
Bailey, E Fiona; Huang, Yu-Hsien; Fregosi, Ralph F (2006) Anatomic consequences of intrinsic tongue muscle activation. J Appl Physiol 101:1377-85
Bailey, E Fiona; Fregosi, Ralph F (2006) Modulation of upper airway muscle activities by bronchopulmonary afferents. J Appl Physiol 101:609-17
Fregosi, R F; Quan, S F; Morgan, W L et al. (2006) Pharyngeal critical pressure in children with mild sleep-disordered breathing. J Appl Physiol 101:734-9
John, Jooby; Bailey, E Fiona; Fregosi, Ralph F (2005) Respiratory-related discharge of genioglossus muscle motor units. Am J Respir Crit Care Med 172:1331-7
Bailey, E Fiona; Janssen, Patrick L; Fregosi, Ralph F (2005) PO2-dependent changes in intrinsic and extrinsic tongue muscle activities in the rat. Am J Respir Crit Care Med 171:1403-7
Bailey, E F; Fregosi, R F (2004) Coordination of intrinsic and extrinsic tongue muscles during spontaneous breathing in the rat. J Appl Physiol 96:440-9
Bailey, E Fiona; Fregosi, Ralph F (2003) Pressure-volume behaviour of the rat upper airway: effects of tongue muscle activation. J Physiol 548:563-8

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