Orthostatic Intolerance in CFS

描述（由申请人提供）：直立不耐受是美国最常见的自主神经障碍，也是慢性疲劳综合征（CFS）中最常见的自主神经表现。慢性疲劳综合症是一种常见的原因不明的疾病，使年轻人丧失能力，在他们最富有成效的岁月。有证据表明，直立不耐受在这些患者的疲劳中起作用。该项目的长期目标是描述慢性疲劳患者站立不耐受的病理生理学和发病机制；探讨直立不耐受在产生疲劳症状中的作用；利用这些信息制定生理上适当的治疗干预措施；从而减少疲劳的症状。有证据表明，一些POTS患者有限制性自主神经病变（神经性POTS），而另一些患者的POTS与自主神经病变无关。这两种变体POTS的病理生理后果尚不完全清楚，然而，有人提出在这两种亚型中一氧化氮的可用性可能不同。具体来说，神经性POTS患者的一氧化氮可用性可能增加，而非神经性POTS患者的一氧化氮可用性可能降低。目前尚不清楚一氧化氮异常是否仅仅是POTS患者的生物学标志物，或者异常是否具有血液动力学和病理生理意义。目前尚不清楚这些病理生理差异是否导致POTS患者对治疗干预反应不理想。应用的具体目的是：在两个独立的实验中，我们将增加和减少一氧化氮的可用性，并检查这种干预对神经性和非神经性POTS的自主心血管影响。我们还将在两种单独的治疗干预中，增加和减少交感神经张力，并检查这些干预对自主心血管的影响、疲劳评分和生活质量的影响。我们预计，对一氧化氮可用性变化的反应和治疗干预措施将在两种POTS亚型中有所不同。公共卫生意义：站立不耐受（体位性心动过速综合征；POTS）是慢性疲劳患者中最常见的自主神经表现。我们将把POTS患者细分为有和没有神经病变的患者，并确定一氧化氮在这两个亚组中所起的作用。我们将测量对治疗的反应以及神经病变和一氧化氮在确定这种反应中所起的作用。

DESCRIPTION (provided by applicant): Orthostatic intolerance is the most prevalent autonomic disorder in the United States and the most common autonomic manifestation in the chronic fatigue syndrome (CFS). CFS is a common disorder of unknown cause that incapacitates young individuals in their most productive years. There is evidence that orthostatic intolerance plays a role in the fatigue of some these patients. The long-term objectives of the project are to delineate the pathophysiology and pathogenesis of orthostatic intolerance in patients with chronic fatigue; to investigate the role of orthostatic intolerance in producing the symptoms of fatigue; to use this information to institute physiologically appropriate therapeutic interventions; and thereby decrease the symptoms of fatigue. There is evidence that some patients with POTS have a restricted autonomic neuropathy (neuropathic POTS) while others have POTS unassociated with an autonomic neuropathy. The pathophysiological consequences of these two variants of POTS are not fully understood, however, it is proposed that nitric oxide availability may differ in these two subtypes. Specifically, neuropathic POTS patients may have increased nitric oxide availability whereas patients with non-neuropathic POTS may have decreased nitric oxide availability. It is not known whether nitric oxide abnormalities are merely a biological marker in POTS patients or whether the abnormalities have hemodynamic and pathophysiological significance. It is also not known whether these pathophysiological differences underlie the unsatisfactory response to therapeutic intervention in POTS patients. The Specific Aims of the application are: in two separate experiments, we will increase and decrease nitric oxide availability, and examine the autonomic cardiovascular effects of this intervention in neuropathic and non- neuropathic POTS. We will also, in two separate therapeutic interventions, increase and decrease sympathetic tone and examine the autonomic cardiovascular effects, fatigue scores, and quality of life in response to these interventions. We anticipate that the responses to changes in nitric oxide availability and the therapeutic interventions will be different in the two POTS subtypes. Public Health Significance: Orthostatic intolerance (the postural tachycardia syndrome; POTS) is the most common autonomic manifestation in patients with chronic fatigue. We will subdivide patients with POTS in to those with and with out neuropathy and determine the role played by nitric oxide in these two subgroups. We will measure the response to therapy and the role played by neuropathy and nitric oxide in determining this response.