Modelling Of The Effects Of Lotronex And Zelnorm On Intestinal Propulsion
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A mathematical model of a segment of the gut to simulate propulsion of a solid pellet (bolus) under physiological conditions and after administration of the drugs – Lotronex (GSK) and Zelnorm (Novartis, AB) – is developed. The gut containing a pellet is represented as a thin deformable soft biological shell with the pellet modeled as a non-deformable solid. Mechanical properties of the gut wall satisfy the general type of nonlinear orthotropy and deformations are finite. Bolus propulsion is numerically simulated by generation and propagation of an electromechanical wave of excitation along the wall. Pharmacological manipulation is applied to model the effects of Lotronex and Zelnorm on the dynamics of bolus progression. The results lead to new quantitative insights into the complex spatio-temporal patterns of gastrointestinal transit. It is demonstrated that the reciprocal relationship in contraction of the longitudinal and circular smooth muscle syncytia is necessary to provide the "mixing" type of movements during the preparatory phase of propulsion. Strong simultaneous contractions of both smooth muscle layers are required to expel the "mixed" pellet from the segment. The model is implemented as an interactive software system, Gut Discovery ©, and accurately predicts the effects of drugs on gut motility. Keywords: pellet propulsion, mathematical model of the gut, effects of drugs. 1 Introduction Despite considerable experimental progress in the past decade in the understanding of the intricate biological mechanisms involved in the regulation of gastrointestinal transit, our conceptual knowledge of the basic processes responsible for intestinal movements is still lacking. This is mainly because of
pellet propulsion, mathematical model of the gut, effects of drugs.