Autonomic Determinants of Postural Tachycardia Syndrome

姿势性心动过速综合征的自主决定因素

基本信息

  • 批准号:
    10473598
  • 负责人:
  • 金额:
    $ 42.33万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2019
  • 资助国家:
    美国
  • 起止时间:
    2019-09-01 至 2024-08-31
  • 项目状态:
    已结题

项目摘要

Abstract Postural tachycardia syndrome (POTS) is a relatively common condition affecting mostly otherwise healthy young women. It is the cause of significant disability and an impairment in quality of life of a magnitude comparable to patients with chronic obstructive pulmonary disease or congestive heart failure but the underlying pathophysiology is heterogeneous. In most patients sympathetic activation is likely an appropriate compensatory response to deconditioning, partial neuropathy or hypovolemia. Our preliminary studies, however, show that a very high salt diet administered under controlled conditions in a metabolic unit does not resolve the volume deficits or sympathetic activation in POTS patients. On the other hand, we have identified a subset of patients with high resting supine central sympathetic outflow, as determined by muscle sympathetic nerve activity (MSNA) above the upper 95% confidence interval for the group. This “primary sympathetic” (psPOTS) subset is associated with a paradoxical increase in upright blood pressure and pressor responses to Valsalva, and appear to improve clinically on central sympatholytics. Thus, our overarching hypothesis is that there is a subset of POTS patients with a central sympathetic activation as the primary pathophysiology. We propose to test this hypothesis in a double blind, placebo-controlled, randomized study using the central sympatholytic moxonidine. If our hypothesis is true, sympathetic inhibition will improve orthostatic symptoms (Specific Aim 1), blood volume (Specific Aim 2). We would expect worsening of all these parameters if sympathetic activation is compensatory in nature. Moxonidine was selected for this proof-of-concept study because it is an effective sympatholytic imidazoline agonist that has less sedative effect compared to older agents. We will also determine if a high salt diet will be a more effective treatment for POTS in the presence of moxnidine. In Specific Aim 3, we propose a complementary approach to determine the central processing gain and peripheral effector gain of sympathetic outflow, by closed loop identification techniques using randomized neck suction and wavelet decomposition to extract individual spikes from sympathetic neurograms. We hypothesize that the central arc gain is higher in psPOTS and can be normalized by sympatholysis with moxonidine. We will also perform a secondary analysis using a logistic model to regress each patient's psPOTS status, as determined by microneurography, against clinical variables, to identify readilly accessible characteristics that can be used clinically to identify hyperadrenergic POTS. We believe the proposed studies will advance this field and ultimately help our patients by improving our current phenotyping capabilities and developing new therapeutic targets. studies will advance this field and ultimately help our patients.
摘要

项目成果

期刊论文数量(2)
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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Andre Diedrich其他文献

Andre Diedrich的其他文献

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{{ truncateString('Andre Diedrich', 18)}}的其他基金

Autonomic Determinants of Postural Tachycardia Syndrome
姿势性心动过速综合征的自主决定因素
  • 批准号:
    9898448
  • 财政年份:
    2019
  • 资助金额:
    $ 42.33万
  • 项目类别:
Autonomic Determinants of Postural Tachycardia Syndrome
姿势性心动过速综合征的自主决定因素
  • 批准号:
    10237867
  • 财政年份:
    2019
  • 资助金额:
    $ 42.33万
  • 项目类别:
ANALYTICAL & PHENOTYPING CORE
分析型
  • 批准号:
    8147957
  • 财政年份:
    2010
  • 资助金额:
    $ 42.33万
  • 项目类别:
Analytical and Phenotyping Core
分析和表型核心
  • 批准号:
    7252850
  • 财政年份:
    2007
  • 资助金额:
    $ 42.33万
  • 项目类别:
Bionic Baroreflex System for Blood Pressure Control
用于血压控制的仿生压力反射系统
  • 批准号:
    6444469
  • 财政年份:
    2002
  • 资助金额:
    $ 42.33万
  • 项目类别:
ANALYTICAL & PHENOTYPING CORE
分析型
  • 批准号:
    8266426
  • 财政年份:
  • 资助金额:
    $ 42.33万
  • 项目类别:
Analytical & Phenotyping Core
分析型
  • 批准号:
    9063593
  • 财政年份:
  • 资助金额:
    $ 42.33万
  • 项目类别:
Analytical & Phenotyping Core
分析型
  • 批准号:
    8293475
  • 财政年份:
  • 资助金额:
    $ 42.33万
  • 项目类别:
Analytical & Phenotyping Core
分析型
  • 批准号:
    8458080
  • 财政年份:
  • 资助金额:
    $ 42.33万
  • 项目类别:
Analytical & Phenotyping Core
分析型
  • 批准号:
    8661207
  • 财政年份:
  • 资助金额:
    $ 42.33万
  • 项目类别:

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