Millions of Americans suffer from diseases of the gastrointestinal tract that cause loss of life, livelihood and well-being. Evidence exists to suggest that many of these diseases may be caused in part by aberrations of blood flow to the mucosa of the gut. Consequently, new methodology is needed to provide direct and reliable information concerning nutrient mucosal blood flow and its role in the pathogenesis of mucosal disease. Our approach to this problem has been to correlate organ blood flow to the cellular and pericellular microenvironment of the superficial mucosa. Using pO2, pH and potential difference (PD) mecroelectrodes, we plan to study the mucosa of the stomach and colon in anesthetized dogs under a variety of pathophysiological conditions. These observations will be correlated will measurements of organ blood flow, arteriovenous oxygen content difference and oxygen consumption as well as histological and biochemical measurements. A series of studies are planned to investigate in the stomach the pathophysiology and treatment of septic and hemorrhagic shock, the mechanisms of subepithelial edema and persistent epithelial hypoxia in the post-shock state, and the oxygen transport and metabolic characteristics of colonic epithelium under normal and ischemic conditions. If the aims of this proposal are successful, new information concerning the pathophysiology of the gastric and colonic mucosa will be described by direct and meaningful observations at the cellular and pericellular level.