Skeletal Muscle Plasticity Following LVAD Support

慢性心力衰竭（CHF）是美国医疗保险患者的主要出院诊断。 虽然药物治疗已导致心脏病患者的死亡率显著降低， 运动不耐症仍然是残疾、发病和生活质量下降的主要原因。 运动性疲劳通常会妨碍规律的体力活动，这可能会导致几种并发症。 疾病和CHF的不良结局。解释运动耐量限制的机制 在CHF是不完全理解。心力衰竭运动不耐受的标志性特征是早期 与骨骼肌肌病有关的乳酸盐产生。大量的问题仍然存在 无人回应也许这些问题中最基本的就是心与人之间是否有直接的联系 和骨骼肌呢这个建议的核心假设是，中央和中央之间存在直接的相互作用。 血液动力学和外周骨骼肌在CHF，这种相互作用将是显而易见的， 中枢血流动力学异常持续正常化。We will study研究humans人类with heart心脏failure衰竭where 通过放置左心室辅助装置 （LVAD）。患者将在LVAD置入前和置入后的时间点接受研究。预言 将在杜克大学至少60名接受LVAD置入的患者中检验中心假设 医学中心同等数量的患者，目前在医院接受非口服药物治疗 CHF的管理将作为比较（对照）组。具体目标是：一。证明 中枢血流动力学的改变足以引起患者外周骨骼肌的变化 关于CHF二.建立从入组到恢复期外周骨骼肌可塑性的程度、类型和时程。 9-术后7周，LVAD支持或药物治疗。确定外围设备的哪些变化以及变化的程度 骨骼肌对LVAD后2周至9周运动耐量变化影响 安置？三. A）检查骨骼肌的潜在循环介质（即肿瘤坏死因子-Q） 在LVAD放置前和放置后的连续时间点发生肌病。B）检查腹直肌的变化 肌肉预LVAD心脏移植，使用特定目标1的选择措施，并比较这些 腿部（股外侧肌）肌肉在可比时间段内的变化。

Chronic heart failure (CHF) is the leading discharge diagnosis among Medicare patients in the United States. Although pharmacologic therapies have resulted in dramatic reductions in mortality in patients with heart failure, exercise intolerance remains a major cause of disability, morbidity, and decreased quality of life. Exertional fatigue often prevents regular physical activity and this may contribute to several co-morbid diseases and the poor outcome from CHF. The mechanisms that account for limitations in exercise tolerance in CHF are not completely understood. The hallmark feature of exercise intolerance in heart failure is early lactate production that is linked with a skeletal muscle myopathy. A large number of questions remain unanswered. Perhaps the most basic of these questions is whether there is a direct link between the heart and skeletal muscle? The central hypothesis in this proposal is that there is a direct interplay between central hemodynamics and peripheral skeletal muscle in CHF, and that this interaction will be evident through a sustained normalization of central hemodynamic abnormalities. We will study humanswith heart failure where abnormalities in central hemodynamics are corrected by the placement of a left ventricular assist device (LVAD). Patients will be studied before, and at time points following LVAD placement. Predictions of the central hypothesis will be tested in a minimum of 60 patients undergoing LVAD placement at Duke University Medical Center. An equal number of patients, currently in the hospital for non-oral pharmacological management of CHF will serve as the comparison (control) group. The Specific Aims are: I. Establish that alterations in central hemodynamics are sufficient to induce changes in peripheral skeletal muscle in patients with CHF. II. Establish the extent, type, and time course, of peripheral skeletal muscle plasticity from entry to 9-weeks post, LVAD support or, medical therapy. Determine which, and to what extent, changes in peripheral skeletal muscle contribute to changes in exercise tolerance from 2-weeks to 9-weeks following LVAD placement? III. A) Examine potential circulating mediators (i.e. tumor necrosis factor-Q)of the skeletal muscle myopathy before, and at serial time points after, LVAD placement. B) Examine changes in rectus abdominus muscle pre-LVAD to heart transplantation, using selected measures from Specific Aim 1, and compare those to changes in leg (vastus lateralus) muscle over a comparable time period.