Burn injuries produce a dramatic array of physiological and biochemical alterations, including: (1) increased energy requirements above the normal metabolic rate; (2) changes in glucose utilization and protein synthesis; (3) changes in blood flow to both the burned area and unaffected organs; and (4) increased tissue permeability at the site of trauma and in multiple other organs. Using invasive techniques, many of these processes have been studied at the organ and tissue level in animals; however, studies in humans are more limited and have involved either whole body measurements or measurements on a restricted number of organs. During the past funding cycle, using PET methods, we have developed, validated and applied new procedures for measuring blood flow, blood volume oxygen utilization and glucose metabolism in a variety of tissues and protein synthesis/degradation in skeletal muscle. Recently, we developed a device for performing some of these measurements at the bedside in critically ill patients. Using these new methods and standard techniques, the hypotheses to be evaluated in this project are: (1) There are tissue-specific energy requirements that are below normal levels in skeletal muscle but 3-4 fold higher in liver and heart. (2) Glucose is taken up into skeletal muscle at or below normal rates and undergoes anaerobic glycolysis to produce lactate alanine and little energy. (3) Protein synthesis is at or below normal levels in muscle and these rates can be modified by anaboli factors. To address these issues, we will measure: (1) regional energy metabolism in various tissues of healthy subjects and patients with burn injuries >15% BSA over the time course after injury; (2) skeletal muscle protein synthesis rates in burn patients; (3) the effects of Oxandrolone treatment on regional glucose metabolism and protein synthesis in convalescent burn patients; and (4) Glucose and fatty acid metabolism in skeletal muscle and other tissues of burned rabbits. To acquire a better understanding of the relationship between the PET measurements of glucose and fatty acid utilization and substrate oxidation, simultaneous steady-state kinetic studies of the metabolic fates of [U-14C] glucose and [1-14C] palmitate will be conducted in these burned and control rabbits.
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