MUSCLE PROTEIN RESPONSE: IMMOBILITY, INJURY & DEPLETION

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The attainment of positive body nitrogen balance during nutritional repletion of catabolic or traumatic illness does not assure restoration of skeletal muscle function or mass. Loss of normal contractile activity (immobility) may alter both whole-body and muscle specific response to nutritional repletion in unstressed hospitalized subjects with intake of amino acids by peripheral tissue (muscle) representing only a small fraction of body nitrogen balance. In such subjects, a progressive reduction in maximal body oxygen uptake is also observed during hospitalization and a submaximal exercise bout results in delayed recovery of muscle protein balance despite adequate nutritional support. The dynamics of muscle protein balance have not been well defined in post-injury patients, but it may be anticipated that the response observed in unstressed subjects would be further disrupted by post-traumatic conditions, where immobility is compounded by neurohumoral and tissue injury factors. Efforts to clarify lean tissue protein responses to immobility, injury, and malnutrition in combination with earlier restoration of muscle protein accrual and function would likely benefit many patients undergoing nutritional support. This proposal will evaluate the impact of intravenous nutritional support upon whole-body and muscle protein metabolism in otherwise unstressed, inactive or exercise-trained subjects and activity-restricted, post-injury patients. Functional (oxygen uptake) capacity and protein metabolism will be evaluated prior to nutritional repletion and at the end of a 10-day period of complete intravenous feeding in non-exercised/repleted of daily submaximal exercise/repleted normal volunteers and patients. Serial evaluations of the metabolic responses to these regimens will include nitrogen and mineral balance, hormonal responses and resting/exercised energy expenditure. Whole-body protein kinetics will be derived from stable isotope infusions (15N-glycine and 13C-leucine). Skeletal muscle protein synthesis will be determined by 13C-leucine enrichment of muscle proteins. Basal extremity flux of amino acids will be performed before and after repletion, and correlations to whole-body and muscle protein kinetics and clearance derived. Skeletal muscle function and composition will be determined by direct measurement of transmembrane potential differences and percutaneous muscle biopsy for assay of amino acid and high energy phosphate concentration. Except for the functional capacity studies, the above techniques will also be applied to patients recovering from mild or moderate traumatic injury in an effort to correlate whole-body and muscle specific responses to injury and nutritional support.