Restoration of Muscle Following Hip Surgery

描述(由申请人提供)：髋部骨折和由此产生的手术修复会导致肌肉质量和功能的显著丧失。损伤和手术本身都会引发一连串的事件，导致肌肉质量的丧失。这个项目的基本前提是，手术中肌肉蛋白的最初损失和随之而来的康复使一般受损的患者容易出现较差的功能或发病率结果。此外，我们认为肌肉蛋白质的丢失是由于肌肉蛋白质代谢的显著变化。这个项目的总体目标是研究旨在改善蛋白质合成和蛋白质分解之间的负肌肉平衡的干预措施。我们推测，这些患者恢复肌肉力量和功能需要肌肉合成代谢的增强。我们首先建议在住院期间使用基本的AM/NO酸配方来恢复肌肉蛋白质的合成。我们进一步提出，手术后高皮质醇血症的改善将导致肌肉蛋白质分解的减少。手术后高皮质醇血症的改善将通过一种常见的抗真菌药物酮康唑来完成，以研究由此产生的对肌肉蛋白质分解的影响。我们将测量瘦体重和肌肉体积，以及手术前和急性住院出院前的功能结果，以确定这些干预措施的有效性。我们将利用稳定同位素方法学来量化急性住院后的肌肉蛋白质代谢。我们还将通过研究蛋白质分解的细胞标记物来证实我们的代谢终点，从而放大这些结果。

DESCRIPTION (provided by applicant): Hip fracture and resultant surgical repair entail a significant loss of muscle mass and function. Both injury and surgery, in and of themselves, initiate a cascade of events which lead to the loss of muscle mass. The general premise of this project is that this initial loss of muscle protein during surgery and the accompanying convalescence predispose a generally compromised patient to poor functional or morbidity outcomes. Further, we propose that muscle protein is lost due to a significant alteration in the muscle protein metabolism. The general goal of this project is to investigate interventions designed to ameliorate the negative muscle balance between protein synthesis and protein breakdown. We hypothesize the enhancement of muscle anabolism is required for these patients to recover muscle strength and function. We first propose to restore muscle protein synthesis throughout hospitalization with the administration of an essential am/no acid formula. We further propose that the amelioration of hypercortisolemia after surgery will result in a decreased muscle protein breakdown. The amelioration of hypercortisolemia after surgery will be accomplished with a common antifungal agent, ketoconazole, in order to investigate the resultant affects on muscle protein breakdown. We will measure lean body mass and muscle volume, as well as functional outcomes before surgery and discharge from acute hospitalization to determine the efficancy of these interventions. We will utilize stable isotope methodology to quantify muscle protein metabolism after acute hospitalization. We will also amplify these results by investigating cellular markers of protein breakdown to corroborate our metabolic endpoints.