Sympathetic Nerve Activity and the Skeletal Myopathy of Heart Failure

交感神经活动与心力衰竭的骨骼肌病

基本信息

批准号：
7754054
负责人：
HOLLY R MIDDLEKAUFF
金额：
$ 38.63万
依托单位：
UNIVERSITY OF CALIFORNIA LOS ANGELES
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-01-15 至 2012-06-30
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): The concept that exercise limitation in patients with chronic heart failure (HF) is directly due to elevated filling pressures or inadequate cardiac output during exercise has been revised. It is now recognized that the skeletal myopathy of HF is an important contributor exercise limitation in HF. The skeletal myopathy of HF is a predictable sequela to chronic cardiac dysfunction. Oxygen transport is a multi-step pathway, and according to the concept of "coordinated adaptation," the development of an abnormality in one step of a multi-step pathway initiates a readjustment of all other steps in the pathway to achieve a new equilibrium, so that all capacities are matched However, the mechanism(s) of "matching capacities," in this case the down- regulation of skeletal muscle capacity and the development of a skeletal myopathy in the setting of severe cardiac disease, remain unknown. We hypothesize that muscle sympathetic activation mediates the skeletal myopathy of HF. This may in part explain why cardiac resynchronization therapy (CRT), a therapy that improves abnormalities of cardiac function, which are not directly related to exercise dysfunction, nonetheless produces an irrefutable increase in exercise capacity. We have preliminary evidence that CRT significantly decreases muscle sympathetic nerve activity (MSNA). The overall goal of this project is to investigate the role of MSNA as the instigator of the skeletal myopathy of chronic HF. Aim 1. To determine the mechanisms of chronic sympathoinhibiton with CRT in HF, and the effect of this sympathoinhibition on the skeletal myopathy. 1.1 Does CRT reduce resting MSNA chronically in advanced HF? 1.2 Is the skeletal myopathy reversed in HF patients in whom MSNA is decreased following CRT? 1.3 Does an increase in baroreceptor gain underlie this decrease in MSNA following CRT? 1.4 Does reversal of the augmented muscle mechanoreceptor sensitivity in HF contribute to the decrease in MSNA following CRT? Aim 2. To determine if another sympatholytic therapy, clonidine, reverses the skeletal myopathy of HF. 2.1 Is the sympatholysis with clonidine associated with a reversal of the skeletal myopathy in HF? 2.2 What is the effect of the improved skeletal myopathy on muscle mechanoreceptor sensitivity in HF?

描述（由申请人提供）：慢性心力衰竭（HF）运动限制的概念直接是由于锻炼过程中的填充压力升高或心脏输出不足所致。现在已经认识到，HF的骨骼肌病是HF的重要促进者运动限制。 HF的骨骼肌病是慢性心脏功能障碍的可预测的后遗症。氧运输是一条多步途径，根据“协调适应”的概念，在多步途径的一步中发展异常的发展启动了实现新均衡的途径中所有其他步骤的重新调整在严重心脏病的情况下，骨骼肌病仍然未知。我们假设肌肉交感神经激活介导了HF的骨骼肌病。这可能部分解释了为什么心脏重新同步疗法（CRT）改善了心脏功能异常的疗法，与运动功能障碍无直接相关，尽管如此，运动能力的增加而无法恢复。我们有初步证据表明，CRT显着降低了肌肉交感神经活性（MSNA）。该项目的总体目标是研究MSNA作为慢性HF骨骼肌病的刺激者的作用。目标1。确定HF中CRT的慢性交感抑制剂的机制，以及这种交感神经抑制对骨骼肌病的影响。 1.1 CRT在晚期HF中长期降低静止的MSNA吗？ 1.2 CRT后MSNA降低的HF患者的骨骼肌病是否反转？ 1.3 CRT后MSNA的减少是压力感受器增益的增加吗？ 1.4 HF中增强的肌肉机械感受器灵敏度的逆转是否有助于CRT后MSNA的降低？目的2。确定另一种交感神经治疗是否可乐定逆转HF的骨骼肌病。 2.1与可乐定的交感神经能与HF中的骨骼肌病的逆转有关？ 2.2改善骨骼肌病对HF肌肉机械感受器敏感性有什么影响？

项目成果

期刊论文数量（10）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Effects of exercise training on neurovascular responses during handgrip exercise in heart failure patients.

运动训练对心力衰竭患者握力运动期间神经血管反应的影响。

DOI：
10.1016/j.ijcard.2010.09.091
发表时间：
2011
期刊：
International journal of cardiology
影响因子：
3.5
作者：
Soares-Miranda,Luisa;Franco,FabioGM;Roveda,Fabiana;Martinez,DanielG;Rondon,MariaUPB;Mota,Jorge;Brum,PatriciaC;Antunes-Correa,LigiaM;Nobre,ThaisS;Barretto,AntonioCP;Middlekauff,HollyR;Negrao,CarlosE
通讯作者：
Negrao,CarlosE

Potential autonomic nervous system effects of statins in heart failure.