Obesity is the most important predictor for obstructive sleep apnea. Although we know that obesity is assoc- iated with a decrease in pharyngeal airway size and an increase in pharyngeal airway collapsibility, we have almost no understanding of how obesity alters the mechanical properties of pharyngeal wall tissues to effect these changes. The PI has developed a novel application of MRI with tissue motion tracking (spatial modul- ation of magnetization, or SPAMM?) to examine the relationships between regional changes in pharyngeal airway size and pharyngeal wall tissue motion in anesthetized rats. Using this innovative technique, we will determine the effects of obesity on pharyngeal mechanics by studying three groups of Zucker rats with different degrees of body fat: lean, obese, and even more obese rats fed a high-fat diet. Our global hypo- thesis is that obesity compromises pharyngeal airway patency through airway narrowing, increased airway collapsibility, and less effective muscle mechanics.
Aim 1 is to determine 1) whether pharyngeal airway compliance and closing pressure progressively increase across age-matched Zucker rats in the order: lean Aim 2 is to determine changes in pharyngeal wall tissue motion for increasingly negative airway pressure up to induced airway collapse. MRI with SPAMM will be performed during application of subatmospheric pressure to the isolated, sealed upper aiway to test 1) whether airway collapse is primarily due to displacement of the anterior pharyngeal wall into the airway, and 2) whether, for a given pharyngeal region, the relationship between pharyngeal wall tissue motion and airway pressure decrements is progress- ively increased across age-matched Zucker rats in the order: lean Aim 3 is to determine pharyngeal wall tissue motion in the 3 groups of Zucker rats during electrical activation of tongue protrudor and retractor muscles. The results will determine whether the relationship between wall tissue displacement and increase in airway size over a range of stimulus intensities is progressively reduced across age-matched Zucker rats in the order: lean >obese >fat augmented obese. The proposed studies will provide new information on how obesity affects pharyngeal mechanics and increase our understanding of why obese patients are predisposed to pharyngeal airway collapse during sleep.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project (R01)
Project #
Application #
Study Section
Respiratory Integrative Biology and Translational Research Study Section (RIBT)
Program Officer
Laposky, Aaron D
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Pennsylvania
Internal Medicine/Medicine
Schools of Medicine
United States
Zip Code
Brennick, Michael J; Kuna, Samuel T; Pickup, Stephen et al. (2011) Respiratory modulation of the pharyngeal airway in lean and obese mice. Respir Physiol Neurobiol 175:296-302
Brennick, Michael J; Pack, Allan I; Ko, Kei et al. (2009) Altered upper airway and soft tissue structures in the New Zealand Obese mouse. Am J Respir Crit Care Med 179:158-69
Xu, Chun; Brennick, Michael J; Dougherty, Lawrence et al. (2009) Modeling upper airway collapse by a finite element model with regional tissue properties. Med Eng Phys 31:1343-8