The hypermetabolic response to injury causes muscle wasting through increased protein breakdown relative to protein synthesis. Muscle wasting increases morbidity and mortality by delaying full-func- tional recovery. Recent clinical studies by our group indicate that the anabolic steroid oxandrolone and the P-blocking drug propranolol decrease protein catabolism in severely burned patients when used over short periods. However, the effects of continuous anabolic agent treatment throughout hospitalization on body composition and functional recovery have not been studied. Our goals are to show that muscle wasting after severe burn can be attenuated by treatment with oxandrolone and/or propranolol. We intend: 1) to determine the effect of oxandrolone and/or propranolol on net muscle protein synthesis, and to relate continued muscle anabolism to improved lean body mass and improved functional recovery in severely burned patients. The hypotheses tested are: a) the acute effect of oxandrolone and/or propranolol on net protein synthesis are sustained throughout hospitaliza tion and b) continued stimulation of net muscle protein synthesis with these drugs improves lean body mass during acute hospitalization, and improves functional outcomes in severely burned children. We also intend: 2) to assess the relationship to oxandrolone and/or propranolol on the molecular effects in skeletal muscle we will test whether: a) Severe burn is associated with decreased myofibrillar mRNA and protein synthesis, a condition which can persist beyond acute hospitalization and b) the accretion of muscle protein in response to oxandrolone and/or propranolol will be primarily myofibrillar and c) the pattern of gene expression changes in response to oxandrolone and/or propranolol.
We aim to show that prolonged treatment with the anti-catabolic agent oxandrolone and/or the anabolic agent propranolol will improve lean body mass and muscular function as well as improve clinical outcomes. Identifying the mechanisms by which these changes take place will provide further basis and support for the use of anabolic agent therapy for catabolic burned children.
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