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Deglutitive and airway protective functions of proximal/ striated muscle esophagus in health and disease

Award Number: R01DK132082
ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Deglutitive and airway protective functions of proximal/ striated muscle esophagus in health and disease - 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.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $469,026 )
2025	2025	THE MEDICAL COLLEGE OF WISCONSIN, INC.	8701 WATERTOWN PLANK RD	MILWAUKEE	WI	53226	MILWAUKEE	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	4	4/18/2025	NON-COMPETING CONTINUATION	$469,026
														Subtotal = $469,026

Issue Date FY: 2024 ( Subtotal = $433,367 )
2024	2024	THE MEDICAL COLLEGE OF WISCONSIN, INC.	8701 WATERTOWN PLANK RD	MILWAUKEE	WI	53226	MILWAUKEE	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	3	5/31/2024	NON-COMPETING CONTINUATION	$433,367
														Subtotal = $433,367

Issue Date FY: 2023 ( Subtotal = $469,026 )
2023	2023	MEDICAL COLLEGE OF WISCONSIN, INC., THE	8701 WATERTOWN PLANK RD	MILWAUKEE	WI	53226	MILWAUKEE	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	2	2/17/2023	NON-COMPETING CONTINUATION	$469,026
														Subtotal = $469,026

Issue Date FY: 2022 ( Subtotal = $451,426 )
2022	2022	MEDICAL COLLEGE OF WISCONSIN, INC., THE	8701 WATERTOWN PLANK RD	MILWAUKEE	WI	53226	MILWAUKEE	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	4/19/2022	NEW	$451,426
														Subtotal = $451,426

Grand Total All Awards = $1,822,845

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Deglutitive and airway protective functions of proximal/ striated muscle esophagus in health and disease

Award Number: R01DK132082

ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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