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

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。大型骨科手术后的肌肉萎缩和虚弱影响康复努力，损害独立性，并延迟重返工作岗位。股四头肌萎缩在髋关节骨关节炎患者的患侧是突出的。股四头肌的萎缩通过髋关节成形术而加剧，使得早在术后5d就明显地进一步损失肌肉和纤维质量。健康受试者的高皮质醇血症和不活动的组合增加了肌肉蛋白质分解到类似于烧伤患者的程度。它也已被证明，简单的手术单独减少肌肉蛋白质的合成。因此，与髋关节成形术相关的肌肉蛋白丢失可能是两种分解代谢机制的结果。 肌肉蛋白质将通过蛋白质合成的抑制和/或通过持续性高皮质醇血症导致的肌肉蛋白质分解的增加而损失。我们建议在髋关节置换术期间研究全身和骨骼肌蛋白质代谢，以确定负责身体蛋白质丢失的代谢机制。此外，我们还提出了可能纠正这些代谢缺陷的干预措施。我们推测，改善皮质激素过多反应和/或刺激肌肉蛋白质合成将保持体内氮。我们提出以下目标。研究/调查：1）髋关节置换术期间骨关节炎和髋部骨折患者的肌肉蛋白质代谢，2）皮质醇合成减少的围手术期影响，3）髋关节置换术期间氨基酸供应对蛋白质合成的影响，4）髋关节置换术期间通过氨基酸给药同时减少皮质醇和刺激蛋白质合成的围手术期影响。

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.