Abnormal Vascular, Metabolic, and Neural Function During Exercise in Heart Failure with Preserved Ejection Fraction

射血分数保留的心力衰竭患者运动期间血管、代谢和神经功能异常

基本信息

  • 批准号:
    10266745
  • 负责人:
  • 金额:
    $ 2.03万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2017
  • 资助国家:
    美国
  • 起止时间:
    2017-05-15 至 2020-08-14
  • 项目状态:
    已结题

项目摘要

PROJECT SUMMARY Heart failure with preserved ejection fraction (HFpEF) accounts for approximately half of the heart failure population in the United States, and the primary chronic symptom experienced by these patients is severe exercise intolerance. Exercise intolerance is quantified as reduced peak oxygen uptake during exercise, and to date, therapies targeting central cardiac limitations have invariably failed to improve peak VO2, quality of life, or survival in HFpEF. Emerging evidence from our lab suggests reduced skeletal muscle oxidative capacity may contribute to exercise intolerance in HFpEF patients. However, the mechanisms responsible for peripheral metabolic inefficiency remain unclear. Reduced blood flow (oxygen delivery), and slowed oxygen uptake kinetics (O2 utilization), may be primary contributors to reduced skeletal muscle oxidative capacity and result in the production of metabolites known to activate muscle afferent nerves and stimulate reflex increases in muscle sympathetic (vasoconstrictor) nervous system activity (MSNA). Elevated MSNA can in turn, result in further impairments in hemodynamic control during exercise. However, to date there have been no studies specifically investigating the contribution of peripheral vascular, metabolic, and neural impairments to reduced exercise capacity in HFpEF. The first goal of this proposal will be to identify impairments in peripheral vascular, metabolic, and sympathetic neural function in HFpEF. To accomplish this, we will measure the dynamic blood flow response (oxygen delivery) and oxygen uptake kinetics (oxygen utilization) during knee extensor (KE) exercise, as well as MSNA during exercise to characterize the contribution of peripheral abnormalities to exercise intolerance in HFpEF. The second goal will be to utilize small muscle mass KE training, specifically targeting these peripheral skeletal muscle deficiencies, to improve aerobic capacity and exercise tolerance in HFpEF. We will assess vascular, metabolic, and neural function before and after completing 8 weeks of single KE exercise training, in conjunction with measures of maximal aerobic capacity and functional capacity. The isolated KE training approach will minimize the central hemodynamic stress of whole body exercise, while simultaneously targeting skeletal muscle function to improve exercise tolerance in HFpEF. Importantly, this proposal will advance our understanding of the basic pathophysiology of exercise intolerance in HFpEF. Considering that vascular function, oxidative capacity, and a MSNA are independent predictors of mortality in heart failure patients, strategies aimed at improving these functional markers may have important implications for the treatment of HFpEF, a condition for which there are currently no known therapies to reduce morbidity and mortality.
项目概要 射血分数保留的心力衰竭(HFpEF)约占心脏的一半 美国的失败人群,这些患者经历的主要慢性症状是 严重的运动不耐受。运动不耐受被量化为峰值摄氧量的减少 锻炼,迄今为止,针对中枢心脏限制的治疗始终未能改善峰值摄氧量, HFpEF 中的生活质量或生存率。我们实验室的新证据表明骨骼肌减少 氧化能力可能导致 HFpEF 患者运动不耐受。然而,这些机制 外周代谢低效的原因尚不清楚。血流量减少(氧气输送),以及 吸氧动力学减慢(氧气利用),可能是骨骼肌减少的主要原因 氧化能力并导致产生已知可激活肌肉传入神经和 刺激反射增加肌肉交感(血管收缩)神经系统活动(MSNA)。高架 MSNA 反过来会导致运动期间血流动力学控制进一步受损。然而,迄今为止 目前还没有专门研究外周血管、代谢和 神经损伤导致 HFpEF 运动能力下降。该提案的首要目标是确定 HFpEF 患者周围血管、代谢和交感神经功能受损。为了实现这一目标, 我们将测量动态血流反应(氧气输送)和摄氧动力学(氧气 利用)在膝伸肌(KE)运动期间,以及运动期间的 MSNA 来表征 外周异常对 HFpEF 运动不耐受的影响。第二个目标是利用 小肌肉质量 KE 训练,专门针对这些外周骨骼肌缺陷,以改善 HFpEF 的有氧能力和运动耐量。我们将评估血管、代谢和神经功能 完成 8 周单次 KE 运动训练之前和之后,结合最大 有氧能力和功能能力。孤立的 KE 训练方法将最大限度地减少中央 全身运动的血流动力学压力,同时针对骨骼肌功能 提高 HFpEF 的运动耐量。重要的是,该提案将增进我们对基本原理的理解 HFpEF 运动不耐受的病理生理学。考虑到血管功能、氧化能力和 a MSNA 是心力衰竭患者死亡率的独立预测因子,旨在改善这些的策略 功能标志物可能对 HFpEF 的治疗具有重要意义,HFpEF 是一种有多种治疗方法的疾病。 目前尚无已知的疗法可以降低发病率和死亡率。

项目成果

期刊论文数量(4)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

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Christopher M Hearon其他文献

Christopher M Hearon的其他文献

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{{ truncateString('Christopher M Hearon', 18)}}的其他基金

Sympathetic neural patterns and transduction in obesity-associated hypertension
肥胖相关高血压的交感神经模式和转导
  • 批准号:
    10877436
  • 财政年份:
    2023
  • 资助金额:
    $ 2.03万
  • 项目类别:
Sympathetic neural patterns and transduction in obesity-associated hypertension
肥胖相关高血压的交感神经模式和转导
  • 批准号:
    10247728
  • 财政年份:
    2020
  • 资助金额:
    $ 2.03万
  • 项目类别:
Sympathetic neural patterns and transduction in obesity-associated hypertension
肥胖相关高血压的交感神经模式和转导
  • 批准号:
    10039251
  • 财政年份:
    2020
  • 资助金额:
    $ 2.03万
  • 项目类别:
Abnormal Vascular, Metabolic, and Neural Function During Exercise in Heart Failure with Preserved Ejection Fraction
射血分数保留的心力衰竭患者运动期间血管、代谢和神经功能异常
  • 批准号:
    9327726
  • 财政年份:
    2017
  • 资助金额:
    $ 2.03万
  • 项目类别:

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