The Design, Operation, and Application of a Dynamic Gastric Model

Abstract

The mechanical functioning of the stomach has been well researched (1). The contractions that mix, break up, and propel the gastric bolus in the main body and antrum have been described in detail and have been partially modeled mathematically. Because the antral forces are particularly important in the mixing and break up of food, they have been measured using manometers, pressure transducers, MRI imaging of agar beads of differing strength (2), and other methods (3, 4). The chemical and biochemical environment of the stomach, its acid and digestive enzymes, and their production and activity rates under different conditions have been studied for many years, and reference ranges established mainly for diagnostic purposes. All these areas have been extensively reviewed (5–7). Despite this understanding of gastric function, many in vitro digestion studies use grossly simplified systems that often include food homogenization, nonphysiological mixing and shear, and unrealistic acid and enzyme concentrations that do not change over time as happens in vivo. This paper describes the design and operation of a computer-controlled dynamic gastric model (DGM) that was built to investigate the effects of the biochemical and physical processing of foods and oral pharmaceuticals. Our intention was to draw together the physical and biochemical features of the human stomach with data on gastric residence time and emptying profiles and to design a computer-controlled mechanical stimulation that works in real time with realistic chewed foods or meals and oral pharmaceutical and nutraceutical products. e-mail: martin@pbltechnology INTRODUCTION The gastric storage, processing, conditioning, and delivery of ingested foods are vital preliminary elements in the delivery of optimal nutrition and the subsequent maintenance of good health. Consequently, the functions of the stomach have been studied extensively in both health and disease with particular attention given to the gastric luminal environment and the dynamic changes that occur in the fed and fasted states. However, such studies are challenging since invasive interventions in humans for the acquisition of gastric contents or the measurement of the physical activity inevitably lead to difficulties, not the least of which are ethical concerns. For example, only liquid meals can be aspirated, and manometric devices, which are difficult to locate, only give limited information on the complex mixing and shearing of the inhomogeneous gastric food bolus. Remote imaging systems and ingestible sensors have added immensely to our understanding of gastric functioning; however, they are slow and expensive. The use of animal models has questions of suitability and ethics, and current in vitro models are often not realistic of human digestion. Nevertheless, such models can provide insights and comparative data. To overcome these experimental and ethical difficulties, several more sophisticated gastric and intestinal simulators have been developed in recent years and have started to provide useful data in areas such as the behavior of functional foods, the survival of probiotics, and the performance of oral drugs (8, 9). The development of physical simulators is being paralleled by in silico mathematical modeling of gastric flow patterns, mixing, and shears, which is particularly useful in understanding the behavior of oral drug formulations if dissolution tests fail to predict in vivo behavior. GENERAL CONSIDERATIONS Food in the stomach is usually a masticated mixture of protein, fat, carbohydrate, indigestible components, micronutrients, non-nutrient phytochemicals, microbiota, and water to which has been added a variable amount of saliva containing enzymes, salts, and bacteria. As such, the gastric food bolus is inhomogeneous at many different levels and retains, at least to some extent, the original structures of the foods consumed. Mastication therefore exposes some nutrients to the immediate effects of the buccal and gastric environment while much remains within the structure of the food bolus delivered to the stomach or the food particles themselves. This masticated mixture is loaded into the gastric compartment over time as we eat. The first food bolus swallowed encounters an acidic environment (pH ≈ 2.0) of residual gastric secretions in the lowest part of the stomach, which may vary in volume up to about 50 mL. Subsequently, as further food is added, the bulk pH usually rises to close to that of the food because of its buffering capacity, although the pH may still be quite *Corresponding author. dx.doi.org/10.14227/DT190312P15