Epidemiological estimates indicate that millions of Americans suffer from peptic diseases of the stomach and duodenum which often produce complications that require surgery. Considerable evidence exists to suggest that ischemia, and by inference cellular hypoxia, may plan a part in the etiology of ulcer disease of the gastric mucosa. Lack of a precise and direct method for studying oxygen availability in the gastric mucosa has produced conflicting information as to the importance of ischemia in loss of mucosal integrity. To obtain new information, we have developed a unique experimental model which employs a "floating" ultramicro electrode technique to determine mucosal intracellular oxygen tension and electrical potential difference in a canine in vivo chambered stomach preparation. Simultaneous measurements of total gastric blood flow, arteriovenous oxygen difference, transmural potential difference and acid secretion can be made and oxygen consumption can be calculated to analyze their relationship to mucosal oxygenation and metabolism. In the first series of experiments we plan to establish normal values for these parameters during resting and acid secretory states. Then we plan a series of studies to investigate the relative effects of tourniquet ischemia, drug-induced ischemia, hypovolemic shock, endotoxemia, mucosal-damaging agents and specific metabolic inhibitors on intracellular oxygenation and metabolism within the gastric mucosa. It is our hypothesis that levels of gastric blood flow required to deliver adequate amounts of oxygen for the metabolic demands of the gastric mucosa will vary with different pathophysiologic conditions. If the aims of this proposal are successful, the fundamental relationship between gastric blood flow, oxygen consumption, availability of oxygen to the mucosa and mucosal metabolism will be described by direct and meaningful observations. These studies hopefully will help us to understand the etiology of ulcerating diseases of the gastrointestinal tract and provide a basis for their prevention and cure.