Esophageal motor function is a key player in both swallowing and airway protection, but these functions
have not been systematically investigated in proximal/striated esophagus (St.Eso) despite its proximity to the
airway and the risk of aspiration due to its dysfunction. Our preliminary studies reveal important novel findings
with significant clinical relevance about St.Eso functions that led to the development of hypotheses to be tested
in this proposal. There are two specific aims in this proposal.
In Specific Aim I we will characterize the St.Eso deglutitive motor function and its modulation by pharyngeal
swallow biomechanics. We will test the following Hypotheses 1) St.Eso. motor function constitutes four distinct
components in relation to its deglutitive excursion associated with laryngeal elevation: a. Increased wall tension
commensurate to the magnitude of its anterosuperior excursion, b. Non-peristaltic bolus receiving function during
UES opening, c. Peristaltic / bolus transport function as it descends and d. Continued peristalsis in its resting
position. 2. Components of St.Eso motor function are correlated with and can be modulated by pharyngeal
biomechanics and related pressures.
SA 1A: In healthy and patient volunteers, we will determine and characterize the: i. non-peristaltic and
peristaltic components of the St.Eso motor functions and their relationship with pharyngeal phase biomechanics,
ii. effect of experimentally enhancing and reducing pharyngeal biomechanics on St.Eso. motor functions, iii.
St.Eso peristalsis parameters and its modulation by bolus type, volume, body positions and age using state-of-
the-art concurrent HRM/impedance manometry/ digital video fluoroscopy and our novel experimental devices.
SA 1B: In our feline model we will: i. characterize the relationship between superior laryngeal excursion
and components of St.Eso motor functions during swallowing, i.e. pre-peristaltic St.Eso wall tension, bolus
injection distance, and peristaltic magnitude, ii. determine the mechanisms of these functions, the possible
mechanisms include ENS and CNS neural reflex control and biomechanical properties of the St.Eso.
In specific Aim 2 we will Characterize the St.Eso. airway protective function and its relationship with that of the
UES and esophageal secondary peristalsis. We will test the following hypotheses: 1) St.Eso. responds to
reflux events independent of secondary peristalsis by a lumen occluding contraction fortifying the UES pressure
response. 2) This response is i. age dependent and is related to the type, quantity, and velocity of the refluxate
and ii. absent or discordant with the UES response in disease states.
SA 2A: In healthy and patient volunteers we will characterize the St.Eso. responses to i. physiologic
reflux, and ii. simulated reflux events (non-acidic and acidic fluids with various volumes and rates).
SA 2B: We will determine in both groups the: i. concordance of St.Eso and UES responses to simulated
and physiologic reflux events, ii. functional relationship of St.Eso. response to that of the secondary peristalsis.