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
- 来源:
- 关键词:AcetyleneActivities of Daily LivingAerobicBlood VesselsBlood flowCardiacCardiac OutputClinicalEFRACEducational InterventionExerciseExercise TestExercise ToleranceExtensorFailureFunctional disorderGasesGoalsHeart failureHumanImpairmentIschemiaKineticsKneeLungMeasurementMeasuresMediatingMetabolicMethodologyMorbidity - disease rateMuscleMuscle ContractionMuscle functionNervous system structureNeurophysiology - biologic functionOutcomeOxygenPatientsPeripheralPopulationProductionQuality of lifeReflex actionRestSkeletal MuscleSpeedStressTechniquesTestingTrainingTreatment EfficacyTreatment FailureUnited StatesVasoconstrictor AgentsWalkingWorkafferent nervedesignexercise capacityexercise interventionexercise intoleranceexercise trainingexperiencehemodynamicsimprovedinsightmortalitymuscle formnovelpatient populationperoneal nervepersistent symptompreservationrelating to nervous systemresponsetargeted treatmentuptakevascular abnormality
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.
项目总结
射血分数保留的心力衰竭约占心脏的一半
美国的失能人群,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在运动过程中峰值摄氧量降低
锻炼,到目前为止,针对心脏中枢限制的治疗总是无法改善峰值VO2,
生活质量,或生存在HFpEF。我们实验室的新证据表明骨骼肌减少
氧化能力可能与HFpEF患者的运动不耐受有关。然而,这些机制
外周代谢效率低下的原因尚不清楚。血流量减少(氧气输送),以及
氧摄取动力学减慢(氧气利用)可能是骨骼肌减少的主要原因
氧化能力和导致代谢物的产生,已知激活肌肉传入神经和
刺激反射增加肌肉交感神经(血管收缩)神经系统活动(MSNA)。高架
MSNA反过来会导致运动过程中血流动力学控制的进一步损害。然而到目前为止,
目前还没有专门研究外周血管、代谢和
HFpEF中运动能力降低的神经损害。这项提案的第一个目标将是确定
HFpEF患者的外周血管、代谢和交感神经功能受损。要做到这一点,
我们将测量动态血流反应(氧输送)和氧摄取动力学(氧
在膝关节伸肌(KE)训练中的利用),以及在训练中的MSNA来表征
外周异常对HFpEF患者运动耐量的影响。第二个目标将是利用
小肌群KE训练,专门针对这些外周骨骼肌缺乏,以改善
高铁高能训练的有氧能力和运动耐量我们将评估血管、代谢和神经功能
在完成8周的单次KE运动训练前和结束后,结合最大
有氧能力和机能能力。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应激,同时靶向骨骼肌功能
提高HFpEF的运动耐量。重要的是,这项建议将促进我们对基本
HFpEF运动耐量异常的病理生理学研究。考虑到血管功能、氧化能力和
MSNA是心力衰竭患者死亡率的独立预测因子,旨在改善这些策略
功能标记物可能对HFpEF的治疗具有重要意义,HFpEF是一种有
目前还没有已知的治疗方法来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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