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The virtual intestine: in silico modeling of small intestinal electrophysiology and motility and the applications

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The intestine comprises a long hollow muscular tube organized in anatomically and functionally discrete compartments, which digest and absorb nutrients and water from ingested food. The intestine also plays key roles in the elimination of waste and protection from infection. Critical to all of these functions is the intricate, highly coordinated motion of the intestinal tract, known as motility, which is coregulated by hormonal, neural, electrophysiological and other factors. The Virtual Intestine encapsulates a series of mathematical models of intestinal function in health and disease, with a current focus on motility, and particularly electrophysiology. The Virtual Intestine is being cohesively established across multiple physiological scales, from sub/cellular functions to whole organ levels, facilitating quantitative evaluations that present an integrative in silico framework. The models are also now finding broad physiological applications, including in evaluating hypotheses of slow wave pacemaker mechanisms, smooth muscle electrophysiology, structure–function relationships, and electromechanical coupling. Clinical applications are also beginning to follow, including in the pathophysiology of motility disorders, diagnosing intestinal ischemia, and visualizing colonic dysfunction. These advances illustrate the emerging potential of the Virtual Intestine to effectively address multiscale research challenges in interdisciplinary gastrointestinal sciences. WIREs Syst Biol Med 2016, 8:69–85. doi: 10.1002/wsbm.1324 This article is categorized under: Analytical and Computational Methods > Computational Methods Physiology > Mammalian Physiology in Health and Disease Models of Systems Properties and Processes > Organ, Tissue, and Physiological Models
The Virtual Intestine modeling framework. The arrows indicate directions of influence and links between the major components of the framework. Electrophysiological models are capable of simulating intestinal slow waves and calcium dynamics, which can be linked to electromechanical models to calculate intestinal motility. Neural models should also present a fundamental level of control, directly and indirectly coregulating mechanical contractions. (Reprinted with permission from Ref . Copyright 2014) Computational fluid dynamics (CFD) models can be linked to three different motility patterns to simulate flow of tracer inside a segment of intestine. Further explanations of this simulation are provided in Figure . Finally, all functional models can be linked to geometric models with realistic anatomy.
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Numerical simulation of the diffusion of a tracer due to different types of contractions. In each case, the tracer was initially located at the upper wall of the intestine. For a longitudinal contraction, the tracer was not transported any significant distance from the wall, regardless of viscosity. A segmental contraction was able to transport the tracer further into the lumen of the intestine, but there was little difference between a low or high viscous fluid. Finally, a combination of a segmental contraction and a longitudinal motion was the most efficient at transporting the tracer into the core of the organ, particularly in the case of a low viscous fluid. Figure courtesy of Drs. Luke Fullard, Wim Lammers, and Maria Ferrua.
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Small intestine and colon anatomically based models. (a) A coupled‐oscillator model applied in an anatomical model of the Visible Human small intestine. (b) A colonic model showing pressure information obtained using high‐resolution manometric catheter from healthy subjects and slow transit constipation patients. In particular, the slow transit patients demonstrated lower pressures over time in the splenic flexure and descending colon compared to the healthy subjects.
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High‐resolution mapping from (26 × 8 electrodes) from the porcine jejunum, distal to the ligament of Treitz. (a) The flexible electrodes were wrapped around the circumference of the intestinal serosa. (b) Intestinal slow waves were processed and displayed as activation (times) map, with red indicating early activation and each isochrone representing a 1‐s interval of propagation. (c) Electrograms at 23 selected recording sites at locations labeled in (b).
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Analytical and Computational Methods > Computational Methods
Models of Systems Properties and Processes > Organ, Tissue, and Physiological Models
Physiology > Mammalian Physiology in Health and Disease

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