This project aims to better understand the processes behind the decrease of intestinal muscle contractility resulting from intestinal interstitial edema. Intestinal edema refers to the excess accumulation of fluid in the interstitial spaces of the intestinal wall tissue. The project focuses on two separate scales. At the continuum scale, the intestinal layer is modeled as an inhomogeneous poroelastic medium that undergoes finite deformation. Intestinal transit is modeled as Navier-Stokes flow within the intestinal cavity and is coupled to the intestinal wall model in a fluid-structure interaction algorithm. Coupling conditions include the continuity of normal fluid flux, the balance of forces and the Beavers-Joseph-Saffman condition, across the interface between the lumen and intestinal layer. At the microscale, a detailed biochemical-mechanical mathematical model of a smooth muscle cell is developed. The model focuses on the regulation of myosin light chain and its phosphorylation, which have been linked to intestinal muscle contractility. Experimental data from both animal and cell models are to be incorporated into the development of the mathematical models at both scales.
Intestinal edema can arise in patients with gastroschisis, inflammatory bowel disease and cirrhosis, as well as in patients receiving resuscitative fluid treatments after traumatic injuries. The main problem for a patient with intestinal edema is that the condition causes ileus, a decrease in intestinal transit due to decreased intestinal smooth muscle contractility. Decreased intestinal transit often leads to longer hospital stays and recovery times for patients and in extreme cases can be fatal. The link between edema and ileus is unknown, and is thus the motivation for developing mathematical models to explore this phenomenon. Results from this project will improve understanding of edema formation and its effect on intestinal muscle contractility and intestinal transit. The models will be utilized to simulate treatment scenarios to assist experimentalists with their goal of preventing ileus when edema forms. There are only a few drugs available to treat ileus; they have limited effectiveness and all target the enteric or central nervous system. This research will be integrated into a Summer math program for high school students. In addition, an important aspect of this collaborative project is the interdisciplinary research experience the postdoctoral fellows and students will obtain as a result of their interactions with the mathematicians and experimentalists.
