Autonomic Dysfunction in Patients with HFpEF
HFpEF 患者的自主神经功能障碍
基本信息
- 批准号:10587484
- 负责人:
- 金额:$ 69.65万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-03-01 至 2027-02-28
- 项目状态:未结题
- 来源:
- 关键词:AccelerationActivities of Daily LivingAddressAdrenergic AgentsAffectAmericanAutonomic DysfunctionBaroreflexBloodBlood PressureBlood VesselsBlood flowBrainBuffersCardiopulmonaryCardiovascular systemCharacteristicsCirculationClinicalDevelopmentDiseaseDissociationDyspneaEFRACExerciseExercise ToleranceExertionFatigueFeedbackFunctional disorderHeart failureImpairmentInfusion proceduresKnowledgeLimb structureMediatingMethodologyMuscleOrganPathologicPathway interactionsPatientsPeripheralPhenotypePhentolaminePhysical activityPlayPrevalencePrognosisQuality of lifeReflex actionRegulationRegulatory PathwayResearchResistanceRestSignal TransductionSkeletal MuscleSympathetic Nervous SystemSymptomsTranslatingTreatment FailureVasomotorWorkalpha-adrenergic receptorantagonistcardiovascular risk factorclinical caredesignexercise intoleranceheart functionhemodynamicsimprovedinnovationinsightmortalityneuromuscularneurovascularpharmacologicprematurepreservationpublic health relevanceresponsesuccesstreatment strategyvasoconstriction
项目摘要
PROJECT SUMMARY: Heart failure with preserved ejection fraction (HFpEF) accounts for greater than 50% of
the 6 million HF cases nationwide, and the prevalence relative to heart failure with reduced ejection fraction
(HFrEF) continues to rise at a rate of 1% per year, presenting an imminent need for further research addressing
the pathophysiology of this pervasive disease. The clinical presentation of HFpEF is defined by dyspnea upon
exertion and severe exercise intolerance, symptoms that are likely due, at least in part, to disease-related
changes in the peripheral circulation. While the mechanisms responsible for the loss of peripheral vascular
control in HFpEF have not been established, sympathetic nervous system (SNS) overactivity is likely to play a
key role. In the peripheral circulation, sympathetic vasomotor outflow causes vasoconstriction via activation of
alpha-adrenergic receptors located on the skeletal muscle vasculature, which serves to constrain limb blood
flow, both at rest and during physical activity. In the presence of pathologic elevations in SNS activity,
exaggerated vasoconstriction may therefore result in insufficient delivery of blood to the exercising muscle,
resulting in exercise intolerance and premature neuromuscular fatigue. As the regulation and functional
consequences of excess sympathoexcitation on vascular control have not been examined in patients with
HFpEF, this proposal seeks to address a significant knowledge gap in our understanding of HFpEF
pathophysiology. Specific Aim 1 is designed to evaluate disease-related changes in the arterial baroreflex,
which is a key regulator of SNS activity. It is hypothesized that that both cardiovagal and sympathetic baroreflex
sensitivity will be reduced, at rest and during exercise, in patients with HFpEF compared to healthy controls.
Both cardiopulmonary and carotid baroreflex responses will be assessed to delineate the impact of HFpEF on
overall arterial baroreflex function. Specific Aim 2 focuses on the transduction of sympathetic outflow in the
peripheral circulation, with the hypothesis that changes in arterial blood pressure and vascular conductance in
response to bursts of SNS activity will be exaggerated in patients with HFpEF. Specific Aim 3 will evaluate the
functional consequences of SNS overactivity at the end organ, utilizing pharmacologic inhibition of alpha-
adrenergic receptors via intra-arterial Phentolamine infusion to block expression of SNS activity. For this Aim, it
is hypothesized that regional alpha adrenergic receptor antagonism will normalize resting and exercising muscle
blood flow, and subsequently improve exercise tolerance and neuromuscular fatigue resistance, in patients with
HFpEF. Upon completion, findings from the proposed work hold the promise of offering new mechanistic insight
regarding HFpEF pathophysiology that may provide a pathway to improved clinical care and, ultimately, better
prognosis in this patient group.
项目总结:射血分数保留的心力衰竭(HFpEF)占50%以上,
全国600万HF病例,以及射血分数降低的心力衰竭的患病率
(HFrEF)继续以每年1%的速度增长,迫切需要进一步研究解决
这种普遍性疾病的病理生理学HFpEF的临床表现定义为:
劳累和严重的运动不耐受,这些症状可能是由于,至少部分是由于疾病相关的
外周循环的变化。虽然外周血管损伤的机制
HFpEF的控制尚未建立,交感神经系统(SNS)过度活动可能在HFpEF中起作用。
关键角色。在外周循环中,交感神经血管流出通过激活
位于骨骼肌血管系统上的α-肾上腺素能受体,用于限制肢体血液
流动,无论是在休息和身体活动。在SNS活性病理性升高的情况下,
过度的血管收缩因此可能导致向运动肌肉输送的血液不足,
导致运动不耐受和过早的神经肌肉疲劳。作为调节和功能
过度交感神经兴奋对血管控制的后果尚未在患有
HFpEF,该提案旨在解决我们对HFpEF理解的重大知识差距
病理生理学具体目标1旨在评价动脉压力感受器反射中的疾病相关变化,
这是SNS活动的关键调节器。假设心迷走神经和交感神经压力感受性反射
与健康对照组相比,HFpEF患者在休息和运动时的敏感性将降低。
将评估心肺和颈动脉压力感受性反射反应,以描述HFpEF对
整体动脉压力反射功能。具体目标2集中在交感神经流出的转导,
外周循环,假设动脉血压和血管传导性的变化,
在HFpEF患者中,对SNS活动爆发的反应将被夸大。具体目标3将评估
SNS过度活动在终末器官的功能后果,利用α-
通过动脉内输注酚妥拉明肾上腺素能受体来阻断SNS活性的表达。为了这个目标,它
假设局部α肾上腺素能受体拮抗作用将使静息和运动肌肉正常化,
血流量,并随后改善运动耐量和神经肌肉疲劳抵抗力,在患者
HFpEF。完成后,从拟议的工作结果举行的承诺,提供新的机制的见解
关于HFpEF的病理生理学,可能提供一种途径,以改善临床护理,并最终更好地
在这个病人群体中。
项目成果
期刊论文数量(0)
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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MARKUS AMANN其他文献
MARKUS AMANN的其他文献
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{{ truncateString('MARKUS AMANN', 18)}}的其他基金
Efficacy of exercise training in patients with HFpEF
运动训练对 HFpEF 患者的疗效
- 批准号:
10700031 - 财政年份:2020
- 资助金额:
$ 69.65万 - 项目类别:
Efficacy of exercise training in patients with HFpEF
运动训练对 HFpEF 患者的疗效
- 批准号:
10063375 - 财政年份:2020
- 资助金额:
$ 69.65万 - 项目类别:
Efficacy of exercise training in patients with HFpEF
运动训练对 HFpEF 患者的疗效
- 批准号:
10327281 - 财政年份:2020
- 资助金额:
$ 69.65万 - 项目类别:
Premature fatigue in veterans with heart failure: neuronal influences
患有心力衰竭的退伍军人过早疲劳:神经元影响
- 批准号:
8730935 - 财政年份:2014
- 资助金额:
$ 69.65万 - 项目类别:
Work of Breathing and Oxidative Stress in COPD: Impact on Blood Flow and Fatigue
慢性阻塞性肺病 (COPD) 中的呼吸和氧化应激作用:对血流和疲劳的影响
- 批准号:
8815194 - 财政年份:2013
- 资助金额:
$ 69.65万 - 项目类别:
Muscle Afferent Feedback Effects in Patients with Heart Failure
心力衰竭患者的肌肉传入反馈效应
- 批准号:
8617297 - 财政年份:2013
- 资助金额:
$ 69.65万 - 项目类别:
Muscle Afferent Feedback Effects In Patients With Heart Failure
心力衰竭患者的肌肉传入反馈效应
- 批准号:
9039133 - 财政年份:2013
- 资助金额:
$ 69.65万 - 项目类别:
Muscle Afferent Feedback Effects in Patients with Heart Failure
心力衰竭患者的肌肉传入反馈效应
- 批准号:
8417378 - 财政年份:2013
- 资助金额:
$ 69.65万 - 项目类别:
Work of Breathing and Oxidative Stress in COPD: Impact on Blood Flow and Fatigue
慢性阻塞性肺病 (COPD) 中的呼吸和氧化应激作用:对血流和疲劳的影响
- 批准号:
8625822 - 财政年份:2013
- 资助金额:
$ 69.65万 - 项目类别:
Work of Breathing and Oxidative Stress in COPD: Impact on Blood Flow and Fatigue
慢性阻塞性肺病 (COPD) 中的呼吸和氧化应激作用:对血流和疲劳的影响
- 批准号:
8598651 - 财政年份:2013
- 资助金额:
$ 69.65万 - 项目类别:
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