Restoration of Muscle Following Hip Surgery

描述（由申请人提供）：髋关节骨折和由此导致的手术修复导致肌肉质量和功能显著丧失。受伤和手术本身都会引发一连串导致肌肉质量损失的事件。该项目的一般前提是，手术期间肌肉蛋白的这种初始损失和伴随的恢复期使一般受损的患者易于出现不良功能或发病结局。此外，我们提出，肌肉蛋白质的损失是由于肌肉蛋白质代谢的显着改变。该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。我们假设这些患者需要增强肌肉张力以恢复肌肉力量和功能。我们首先建议恢复肌肉蛋白质的合成在整个住院管理的一个重要的am/no酸公式。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减少。手术后高皮质醇血症的改善将使用常见的抗真菌剂酮康唑完成，以研究对肌肉蛋白分解的影响。我们将在手术前和急性住院出院前测量瘦体重和肌肉体积以及功能结局，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志物来扩大这些结果，以证实我们的代谢终点。

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.