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Biology subjects

Fernandes, S. Q.

Publications and source records attributed to Fernandes, S. Q..

2 recordsLinked to original sources

Impact of Slow Wave Abnormalities and Impaired Coordination of Pyloric Closure and Antral Contraction on Gastric Emptying: A Compartmental Modeling Study

PurposeTo develop a computationally efficient gastric compartmental model that simulates diseased stomach function by altering antral-pyloric coordination and "slow wave" properties. The model evaluates motility, gastric emptying and mixing. The computational efficiency of the model enables broad parameter sweeps to simulate various pathological conditions, offering an alternative to computationally expensive finite element or finite volume approaches. MethodsWe developed an extended compartmental model to simulate gastric function under dysrhythmic conditions. Building on prior work, this framework incorporates enhanced fluid flow equations and improved inter-compartment connectivity. These modifications enable simulation of impaired antro-pyloric coordination, regional variations in "slow wave" frequency (bradygastria, tachygastria), and reduced amplitude to mimic quiescent activity. Model outputs included gastric emptying rates, mixing efficiency, and transpyloric flow events across healthy and impaired conditions. ResultsSimulations demonstrated that abnormal "slow wave" frequency or amplitude delays gastric emptying and diminishes mixing efficiency. Bradygastria induced retrograde transpyloric flow, reflecting backflow from intestine to stomach, a pathological marker. These disruptions were most pronounced when antro-pyloric coordination was impaired. Predictions aligned with prior experimental and computational findings, while model execution was ~ 50-fold faster than real-time gastric dynamics, highlighting computational efficiency. ConclusionThis physiologically inspired compartmental model captures the impact of "slow wave" abnormalities on gastric motility. By reproducing impaired flow and mixing patterns characteristic of diseased states, it provides a valuable tool for probing mechanisms of gastric dysfunction. Importantly, its computational efficiency positions the model for use in developing and rapid testing of model-based, closed-loop neurostimulation therapies for gastrointestinal disorders.

biophysics↗

A Compartmental Model for Simulating the Gut-Brain Axis in Gastric Function Regulation

Gastric function is regulated by the gut-brain axis, which integrates vagal and enteric nervous system (ENS) pathways. The parasympathetic circuit within the vagal pathway promotes digestion by stimulating peristaltic activity and relaxing the Pyloric sphincter (PS) through motor and sensory neurons. In contrast, the sympathetic pathway inhibits digestion by suppressing peristalsis and constricting the PS, highlighting the complex neural coordination involved in gastric regulation. This study introduces a novel mathematical model of the gut-brain axis using a computationally efficient compartmental framework. The model simulates the vagal and ENS pathways and their corresponding effects on gastric function to improve our understanding of gut-brain axis regulation. The model employs the Michaelis-Menten equation with a Hill coefficient (MMEHC) equation to capture neurotransmitter release at neuromuscular junctions by stimulation of motor neurons and its effects on gastric cells. Motor (efferent) neurons are modeled for three key stomach regions: the fundus (tonic activity), antrum (phasic activity), and PS (both tonic and phasic activity). Thus, the stomach is represented as a three-compartment model. The stomach model extends our previous work (Fernandes et al., 2024) by incorporating passive stress and dynamic changes in stomach geometry. Sensory (afferent) inputs are represented through linear equations that account for chemo- and mechanoreceptor activity, while a binary variable captures the sympathetic response. Afferent and efferent firing rates are linked via fitted curves to effectively close the gut-brain axis feedback loop, borrowing from a similar approach used to model cardiovascular regulation. The simulation results align with physiological observations, demonstrating inhibitory digestive activity during sympathetic responses and excitatory activity, such as gastric emptying, during parasympathetic responses. During gastric emptying, the Interstitial Cells of Cajal (ICC) activity shows constant amplitude for low to medium gastric volumes but exhibits an increase in amplitude at very high gastric volumes. Furthermore, gastric emptying rates decrease with high-calorie liquids due to PS regulation, validating the potential of the model for studying Gastrointestinal (GI) disorders and developing vagal-based therapies.

biophysics↗