RESTORATION OF MUSCLE PROTEIN, MASS, AND STRENGTH AFTER HIP SURGERY/HIP FRACTURE

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。大型骨科手术后肌肉萎缩和无力会影响康复努力，损害独立性，并延迟重返工作岗位。股四头肌萎缩是显著的患者患侧骨关节炎髋。髋关节置换术加剧了股四头肌萎缩，因此，早在术后5d肌肉和纤维质量的进一步损失就很明显。在健康受试者中，高皮质醇血症和缺乏运动的结合增加了肌肉蛋白分解，其程度与烧伤患者相似。也有证据表明，单纯的手术会减少肌肉蛋白质的合成。因此，与髋关节置换术相关的肌肉蛋白损失可能是两种分解代谢机制的结果。肌肉蛋白会因抑制蛋白质合成和/或持续高皮质醇血症导致肌肉蛋白分解增加而丢失。我们建议在髋关节置换术中研究全身和骨骼肌蛋白质代谢，以确定导致身体蛋白质损失的代谢机制。此外，我们提出干预措施，以潜在地纠正这些代谢缺陷。我们假设高皮质醇反应的改善和/或肌肉蛋白质合成的刺激将保存体内氮。我们提出以下目标。研究/探讨：1)骨关节炎和髋部骨折患者在髋关节置换术中肌肉蛋白质代谢的变化；2)皮质醇合成减少对围术期的影响；3)整个髋关节置换术中氨基酸供应对蛋白质合成的影响；4)髋关节置换术中氨基酸同时减少皮质醇和刺激蛋白质合成的影响。

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.