Cardiovagal baroreflex deficits impair neurovascular coupling and cognition in Postural Tachycardia Syndrome

项目摘要/摘要 体位性心动过速综合征(POTS)是一种慢性立位不耐受形式，与过度 直立性心动过速，主要发生在年轻女性(&gt；85%)。它最令人不安的症状是 头晕、疲劳和记忆力减退常被患者称为“脑雾”。与任务相关 神经血管偶联(NVC)将神经活动与CBF的增加联系在一起，即所谓的“功能性充血”。 尽管POTS组的记忆任务成绩和NVC随着倾斜角的增加而恶化，但不是健康对照组， 脑血流量(CBF)与对照组相似。相反，我们观测到了大范围的窄带低空。 血压(OBP)中的频率(0.07-0.13赫兹)振荡，引起并放大CBF(OCBF)中的振荡。 OBP和OCBF随倾斜角度增加而增加，并导致工作记忆受损和功能减退 充血。心迷走神经压力感受性反射将血压耦合到心率，以缓冲血压变化。我们假设 心脏迷走神经压力感受器反射在盆内直立时逐渐受损，但在健康志愿者中不是这样。 并解释了OBP、OCBF和NVC的损失；此外，改善压力反射可以减少OBP、OCBF和 罐子里的脑雾。 我们将招募15-30岁的女性POTS受试者(N=60)，停止药物治疗，不接受其他系统治疗 疾病和健康受试者(N=20)。我们的方法有三个方面：1)我们将使用参考标准 改良Oxford技术测量心脏迷走神经压力感受性反射，评估工作记忆和功能 充血时，POTS和健康受试者经历从仰卧到60度的分级直立倾斜，以15度为增量。 我们预计POTS中低频率的OBP和OCBF会逐步增加，而OCBF会逐步减少 功能性充血与N-back记忆任务的表现2)我们将外力OBP和OCBF 用下体负压振荡论证OCBF与OCBF的因果关系 减少功能性充血和在N-back记忆任务中的表现3)我们将比较急性 使用上述方法1)的实验方法，研究地高辛和吡斯的明对安慰剂的影响。 文献表明，这些药物增加心脏迷走神经压力感受性反射和改善副交感神经张力。 疾病和健康；它们可以减少心动过速和锅的症状。这项工作不仅将提供一种 POTS患者心脏迷走神经压力感受性反射受损与认知丧失之间的联系，但可能在不同的方面适用 出现压力反射障碍的循环系统疾病。

Project Summary/Abstract Postural tachycardia syndrome (POTS), is the chronic form of orthostatic intolerance associated with excessive upright tachycardia, and occurs predominantly in young females (>85%). Among its most troubling symptoms are lightheadedness, fatigue, and decreased memory often called “brain fog” by patients. Task-related neurovascular coupling (NVC) links neural activity to an increase in CBF known as “functional hyperemia”. Although memory task performance and NVC deteriorated with angle of tilt in POTS but not healthy controls, cerebral blood flow (CBF) remained similar to control. Instead, we observed extensive narrow band low frequency (0.07-0.13 Hz) oscillations in BP (OBP) that entrained and amplified oscillations in CBF (OCBF). OBP and OCBF increased with tilt angle and caused impaired working memory and reduced functional hyperemia. The cardiovagal baroreflex couples BP to HR to buffer BP changes. We hypothesize that the cardiovagal baroreflex becomes progressively impaired with orthostasis in POTS, but not in healthy volunteers, and accounts for OBP, OCBF, and loss of NVC; further, improving the baroreflex reduces OBP, OCBF and Brain Fog in POTS. We will recruit female POTS subjects aged 15-30 years (N=60) off medication and free of other systemic disease, and healthy subjects (N=20). Our approach is three-fold: 1) we will use the reference standard modified Oxford technique to measure the cardiovagal baroreflex, and assess working memory and functional hyperemia while POTS and healthy subjects undergo a graded upright tilt from supine to 60o in15o increments. We anticipate step-wise increased OBP and OCBF at low frequency in POTS, with step-wise decreased functional hyperemia and performance on an N-Back memory task 2) We will externally force OBP and OCBF using oscillatory lower body negative pressure to demonstrate the causal connection between OCBF and decreased functional hyperemia and performance on an N-Back memory task 3) We will compare the acute effects of digoxin and pyridostigmine, against placebo using the experimental methods of approach 1) above. Literature suggest that these drugs increase cardiovagal baroreflex and improve parasympathetic tone in sickness and in health; they may reduce tachycardia and symptoms in POTS. This work will not only furnish a link between impaired cardiovagal baroreflex and cognitive loss in POTS, but may find applicability in diverse circulatory illnesses in which baroreflex deficits appear.