Oral rehydration solutions (ORS) presently in use are effective for the treatment of diarrhea, especially early in life. Current ORS reverse dehydration and sodium (Na) losses, although they do not shorten the duration of the disease. This revised proposal is designed to extend preliminary investigations which showed that certain viscous agents improved ORS capacity for rehydration and Na uptake. We now aim to broaden our observations and substantiate the general hypothesis that the effectiveness of ORS can be enhanced by soluble fibers or gums which alter the rheological characteristics of the intestinal lumen contents. To achieve this goal we will study the role of viscosity, net charge and polymer chain organization at different Na concentrations. We will also examine whether water absorption improvement is due to a reduction of fluid recirculation into the lumen associated with changes in the architecture of the mucosal brush border. An important component of the project is the use of several animal models of childhood gastrointestinal disease and malnutrition which mimic presentations of diarrheal disease in human populations. They include: (1) secretory diarrhea induced by stable E. coli toxin; (2) in situ exposure of the small intestine to theophylline, which acts by the same mechanisms as cholera toxin; (3) protein-energy malnutrition (PEM); (4) a combination of PEM and toxin-induced secretion. The basic experimental technique will be an intestinal perfusion procedure in anesthetized rats. Nonabsorbable markers and labeled tracers will enable us to calculate net and unidirectional flows of water and other ORS components. We will also evaluate the effectiveness of soluble fiber- enhanced ORS in reversing the effects of secretagogues on the intestinal villi and the brush border vicinity by histologic and electron microscopic methods. Quantitative data obtained with intestinal perfusions in rats under anesthesia have been shown to parallel results reported in children with diarrhea treated with the same ORS. This proposal should provide the basis for a new approach intended to make ORS a more effective and economically accessible therapy in the treatment of diarrhea and dehydration, particularly in infancy and childhood.
