Loss of body nitrogen during catabolic or traumatic illness is often reversible by the provision of enteral or parenteral nutrition. Despite the attainment of positive nitrogen balance during nutritional support, there is little prospective data to suggest that maintenance or restoration of skeletal muscle mass is readily achieved in the hospitalized patient. As the ultimate functional capacity of the patient is dependent upon integrity of the skeletal muscle mass, optimal methods to achieve skeletal muscle protein synthesis would benefit many nutritionally-supported patients. This proposal is an extension of recently completed studies which evaluated whole-body and in vivo skeletal muscle protein metabolism in nutritionally depleted, but otherwise healthy hospitalized volunteers. Evaluation of muscle function (work) capacity in mildly to moderately malnourished normal volunteers and patients before and during intravenous nutritional support will be undertaken. Concurrent studies to determine whole-body protein kinetics (using infusions of 15N-glycine) and of skeletal muscle flux of amino acids, before and during nutritional support, will be performed. Methods to assay in vivo skeletal muscle protein synthesis (using 1-13-C-leucine) will also be developed and applied to study subjects. During the final 2-3 years of studies in both normal subjects and depleted patients, a program of endurance training, using daily submaximal exercise, will be employed to assess the impact of enforced contractile activity upon muscle function and protein synthesis. It is anticipated that these studies will provide additional insight into several areas of importance to nutritional support technology. Further understanding of the impact of """"""""unstressed"""""""" hospitalization and consequent detraining (muscle disuse) effects will be gained. The relative contribution of intravenous nutritional support to the reversal of a detraining phenomenon will also be described. The potential for submaximal exercise to reverse or ameliorate detraining effects by an impact on wholebody and/or muscle tissue protein metabolism will be evaluated. Finally, further insight into optimal nutrient requirements of both normal subjects and patients during an endurance training program will be gained. The results obtained in the above areas may be applied to rehabilitation programs favoring early restoration of functional capacity in malnourished patients.
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