Skeletal Muscle Plasticity Following LVAD Support

LVAD 支持后的骨骼肌可塑性

• 批准号: 7028867
• 负责人: BRIAN H ANNEX
• 金额: $ 41.52万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-04-01 至 2009-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7028867
• 关键词: auxiliary heart prosthesis; biopsy; cardiovascular disorder therapy; cardiovascular surgery; chronic disease /disorder; clinical research; exercise; heart failure; hemodynamics; histology; human subject; human therapy evaluation; medical implant science; muscle function; patient oriented research; postoperative state; striated muscles; tumor necrosis factor alpha

DESCRIPTION (provided by applicant): 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 humans with 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.

描述（由申请人提供）：慢性心力衰竭（CHF）是美国医疗保险患者的主要出院诊断。尽管药理疗法导致心力衰竭患者的死亡率急剧降低，但运动不耐受仍然是残疾，发病率和生活质量降低的主要原因。劳累疲劳通常会阻止定期的体育锻炼，这可能会导致多种合并症和CHF的不良结果。尚不完全理解解决CHF运动耐受性限制的机制。心力衰竭运动不耐受的标志性特征是早期乳酸产生，与骨骼肌肌病有关。许多问题仍然没有解决。也许这些问题中最基本的问题是心脏和骨骼肌肉之间是否有直接的联系？该提议中的中心假设是，中央血流动力学与周围骨骼肌之间存在直接相互作用，并且通过持续的中央血液动力学异常的正常化，这种相互作用将显而易见。我们将研究心力衰竭的人类，其中通过放置左心室辅助装置（LVAD）来纠正中央血液动力学异常。将在LVAD放置后的时间点进行研究。中央假设的预测将在杜克大学医学中心至少60名接受LVAD安置的患者中进行测试。目前在CHF非口腔药理学管理医院的患者数量相等，将作为比较（对照）组。具体目的是：I。确定中央血液动力学的改变足以诱导CHF患者的外周骨骼肌的变化。 ii。从进入到9周，LVAD支持或医疗疗法的外周骨骼肌可塑性的程度，类型和时间过程。确定在LVAD放置后，周围骨骼肌的哪个以及在多大程度上有助于从2周变为9周的运动耐受性的变化？ iii。 a）在骨骼肌肌病之前和在串行时间点上，检查了骨骼肌肌病的潜在循环介质（即肿瘤坏死因子-Q）。 b）使用特定目标1的选定措施检查腹肌肌肉前肌肉前肌肉的变化，并将这些措施与相当的时间内的腿（股外侧）肌肉的变化进行比较。