Reducing Orthostatic Intolerance with Oral Rehydration in Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

 描述（由申请人提供）：我们和其他人已经证明，大多数患有肌痛性脑脊髓炎/慢性疲劳综合征（ME/CFS）的年轻患者具有直立不耐受（OI），无法耐受直立应激，如长时间站立。ME/CFS中的OI包括体位性心动过速综合征（POTS）和神经介导性低血压（NMH），前者症状沿着直立心率加快，后者症状沿着血压直立下降。OI的原因多种多样，但显然是由500-800 mL血液从上身到下身的重力移位引起的中心血容量（BV）的姿势收缩引起的。无论病因如何，使用等渗盐水进行静脉中心BV扩张通常有效地用于减少OI，但如果长期使用则会出现并发症。口服水化的替代形式不能提供类似的益处。有趣的是，一种特定的等渗口服补液溶液（ORS W.H.O.）利用葡萄糖和钠的共转运，已经显示出有效地使霍乱患者再水合，这表明增加中心BV的能力与静脉内液体相竞争。由于生理盐水或ORS BV扩张的循环效应尚未完全了解，我们建议研究伴有POTS或NMH的ME/CFS患者在立位应激期间液体负荷的神经血管生理学，并将结果与健康对照受试者进行比较。我们假设等量口服补液盐在增加血管内和间质液容量和提高立位耐受性方面并不劣于静脉输注生理盐水，可能是上级的。使用Finapres和血压测量法、惰性气体再呼吸法测量心输出量和外周动脉阻力、经颅多普勒超声测量脑血流速度、阻抗法和静脉闭塞体积描记法测量局部液体移位，我们获得了ME/CFS伴OI患者的初步数据，证明ORS具有上级立位耐力恢复。我们将招募年龄在15-29岁的确诊ME/CFS伴OI的患者，包括15例NMH和15例POTS，并将其与15例健康志愿者进行比较。在特定目标1中，我们将在通过逐步下体负压（LBNP）施加直立应力之前通过Daxor碘化白蛋白技术测量BV，以测量OI的阈值。将OI患者中使用系列血细胞比容的BV相对变化与来自类似测试的对照受试者的数据进行比较。在特定目标2中，所有受试者将在交叉研究中随机接受生理盐水或ORS。在一天内，在完成1升静脉生理盐水输注或ORS给药前和给药后1小时，测量患者和对照受试者的总BV和神经血管特性。在另一天（间隔1周），我们将使用其他水合途径重复测量。我们将在生理盐水或ORS后的每一天进行LBNP，以确定立位不耐受和循环生理学是否与等容量IV生理盐水或ORS水化类似地得到改善。

 DESCRIPTION (provided by applicant): We and others have shown that a majority of younger patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) have orthostatic intolerance (OI), the inability to tolerate orthostatic stress such as prolonged standing. OI in ME/CFS comprises postural tachycardia syndrome (POTS) in which symptoms occur along with excessive upright heart rate, and neurally mediated hypotension (NMH) in which symptoms occur along with an upright fall in blood pressure. The causes of OI are diverse but are clearly initiated by postural contraction of central blood volume (BV) by gravitational translocation of 500-800 mL of blood from the upper to the lower body. Intravenous central BV expansion with isotonic saline is commonly and effectively used to reduce OI regardless of etiology, but has complications if used long term. Usual forms of oral hydration fail to provide similar benefit. Interestingly, a specific isotonic oral rehydration solution (ORS W.H.O. formula), making use of co-transport of glucose and sodium, has been shown to efficiently rehydrate cholera patients suggesting an ability to increase central BV rivaling intravenous fluids. Since the circulatory effects of saline or ORS BV expansion are incompletely understood, we propose to study the neurovascular physiology of fluid loading during orthostatic stress in ME/CFS patients with POTS or NMH, comparing results with healthy control subjects. We hypothesize that equal volumes of ORS is not inferior and may be superior to intravenous saline infusion in increasing intravascular and interstitial fluid volume and improving orthostatic tolerance. Using noninvasive measurements of heart rate and blood pressure by Finapres and oscillometry, cardiac output and peripheral arterial resistance by inert gas rebreathing, cerebral blood flow velocity by transcranial Doppler ultrasound, and regional fluid shifts by impedance and venous occlusion plethysmography, we have acquired preliminary data in ME/CFS patients with OI demonstrating superior restoration of orthostatic tolerance with ORS. We will recruit patients aged 15-29 years who have confirmed ME/CFS with OI, including 15 with NMH and 15 with POTS, and compare them to 15 healthy volunteer subjects. In Specific Aim 1 we will measure BV by Daxor iodinated albumin technique before orthostatic stress imposed by step-wise lower body negative pressure (LBNP) to measure the threshold for OI. Relative changes in BV using serial hematocrits in OI patients will be compared to data from control subjects similarly tested. In Specific Aim 2, all subjects will be randomized to receive saline or ORS in a cross over study. On one day, total BV and neurovascular properties will be measured in patients and control subjects before and 1 hour after completing one liter administration of intravenous normal saline infusion or ORS. On another day (separated by 1 week), we will repeat measurements using the other hydration route. We will perform LBNP on each day following saline or ORS to determine whether orthostatic intolerance and circulatory physiology are improved similarly with equivolumic IV saline or ORS hydration.