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。 尽管药物治疗显著降低了心脏病患者的死亡率 失败、运动不耐受仍然是残疾、发病率和生活质量下降的主要原因。 疲劳性疲劳常常妨碍有规律的体力活动，这可能导致几种共病。 疾病和充血性心力衰竭的不良结局。运动耐量受限的机制 对慢性心力衰竭的研究尚不完全清楚。心力衰竭患者运动不耐受的显著特征是早期 乳酸的产生与骨骼肌病有关。仍然有大量的问题存在 无人接听。也许这些问题中最基本的问题是心脏和心脏之间是否存在直接联系 那骨骼肌呢？这一提议的中心假设是，在中央和中央之间存在直接的相互作用 CHF的血流动力学和外周骨骼肌之间的相互作用将通过 中枢血流动力学异常持续正常化。我们将研究患有心力衰竭的人类 中心血流动力学的异常可以通过放置左心室辅助装置来纠正 (LVAD)。患者将在放置LVAD之前和之后的时间点进行研究。对未来的预测 中心假说将在杜克大学接受LVAD安置的至少60名患者中进行测试 医疗中心。同等数量的患者，目前在医院接受非口腔药物治疗 CHF管理人员将作为对照(对照)组。具体目标是：一、确立 中枢血流动力学的改变足以引起患者周围骨骼肌的改变 患有CHF。建立周围骨骼肌可塑性的范围、类型和时间进程 9周后，LVAD支持或药物治疗。确定外围设备中的哪些更改以及更改程度 骨骼肌对左前降支术后2周至9周运动耐量的改变有贡献 安置？三、a)检查骨骼肌潜在的循环介质(即肿瘤坏死因子-Q) LVAD放置前、后连续时间点的肌病。B)检查腹直肌的变化 使用特定目标1中选择的措施，从左冠状动脉前瓣到心脏移植，并比较 与腿部(股外侧肌)肌肉在可比时间段内的变化有关。

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.