Project 2: In-Vivo

Aim 1: To investigate physiologic mechanisms of the esophageal response to distension.

Aim 2: To investigate luminal distensibility as a variable characterizing esophageal disease severity.

• We hypothesize that distension-induced esophageal contractility is mediated via a delicate interplay between wall mechanics and the excitatory and inhibitory neural pathways of smooth muscle control.
• Our preliminary data using innovative FLIP techniques revealed that the esophagus will respond to volumetric distention by generating repetitive antegrade contractions in normal subjects.
• The threshold for eliciting the contractile response is likely determined by the underlying mechanics of the wall as the stimulus is related to wall-tension that is generated by deformation and IBP.
• Experiments will be designed to study the effect of cholinergic influence on esophageal distensibility in patients with varying degrees of compromised wall mechanics.

• We hypothesize that an altered response to volumetric distention is a primary determinant of esophageal symptoms. Both reduced and increased esophageal wall distensibility can dramatically alter the dynamics of bolus transport and thus, will lead to symptoms and complications
• Additionally, altered contractile responses focused on the generation of RACS can also alter esophageal clearance and predispose the patient to aspiration and malnutrition.
• Our goal will be to determine the link between these responses and outcomes in well-defined patient populations using our novel HRIM metrics derived from the 4 phases of swallowing model and Panometry analysis.