Studies from recent years demonstrate that the systemic metabolic response to burn injury has an important local component which is unique to the region of the burn. We have studied this local response in rats following a single hind limb scald which is limited to 6-7% body surface area. We have demonstrated that during the recovery phase (3 days post-burn) a spectrum of metabolic alterations is observed in skeletal muscle from the burned limb, but not in the contralateral muscle from the unburned limb, suggesting that changes in muscle beneath the burn wound are independent of the alterations in the systemic metabolic and endocrine environment. The changes in muscle from the burned limb include increased glucose uptake and lactate release, increased rates of protein degradation and protein synthesis, and development of a post-receptor unresponsiveness of muscle to insulin as evidenced by inability of this hormone to stimulate glucose and amino uptakes, and glycogen synthesis. We propose to extend these studies on chronic metabolic alterations in muscle during the post-burn recovery phase and focus the investigation on two clinically relevant consequences of local thermal injury: unresponsiveness to insulin and accelerated protein turnover.
The specific aims of this research are: (a) to test whether the accelerated protein turnover in skeletal muscle underlying the burn wound contributes to post-burn hypermetabolism; (b) to measure the effect of insulin on protein synthesis and degradation by muscles underlying, and remote from, the burn wound; (c) to evaluate whether the development of insulin unresponsiveness in muscle beneath the burn wound is related to tissue energy status or intracellular insulin degrading activity; (d) to test whether the accelerated protein turnover in muscle beneath the burn wound is due to altered tissue sensitivity to glucocorticoids and androgens, increased content of cellular calcium observed in this muscle, or energy status of muscle cells. It is anticipated that data generaged by this project will aid in the development of scientifically sound nutritional therapy of burned patients which will taken into account the special nutritional needs of the region of the burn.
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