This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Muscle wasting and weakness after major orthopedic surgery affects rehabilitative efforts, compromises independence, and delays the return to work. Quadriceps muscle wasting is prominent in the affected side of patients with osteoarthritic hips. The atrophy of quadriceps muscle is exacerbated by hip arthroplasty, such that further loss of muscle and fiber mass is evident as early as 5d post-operatively. The combination of hypercortisolemia and inactivity in healthy subjects increases muscle protein breakdown to a degree analogous to burn patients. It has also been demonstrated that uncomplicated surgery alone decreases muscle protein synthesis. Thus, the loss of muscle protein associated with hip arthroplasty is potentially the result of two catabolic mechanisms. Muscle protein will be lost by the inhibition of protein synthesis, and/or through the increase in muscle protein breakdown resulting from persistent hypercortisolemia. We propose to study whole-body and skeletal muscle protein metabolism during hip arthroplasty to ascertain the metabolic mechanisms responsible for loss of body protein. Further, we propose interventions to potentially correct each of these metabolic deficiencies. We hypothesize that the amelioration of the hypercortisolemic response and/or the stimulation of muscle protein synthesis will preserve body nitrogen. We propose the following aims. To study/investigate: 1) muscle protein metabolism in patients with osteoarthritis and hip fracture during hip arthroplasty, 2) the perioperative effects of diminished cortisol synthesis, 3) the effects of amino acid provision throughout hip arthroplasty on protein synthesis, 4) the perioperative effects of concurrent diminished cortisol and stimulated protein synthesis by amino acid administration during hip arthroplasty.
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