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

心脏迷走性压力反射缺陷损害姿势性心动过速综合征的神经血管耦合和认知

基本信息

批准号：
9358891
负责人：
JULIAN M STEWART
金额：
$ 62.65万
依托单位：
NEW YORK MEDICAL COLLEGE
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-07-01 至 2021-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9358891
关键词：
Acute Age American Back Baroreflex Blood Pressure Brain Buffers Cerebrovascular Circulation Cerebrum Chronic Cognition Confusion Core-Binding Factor Couples Defect Digoxin Doppler Ultrasound Dose Fatigue Female Fogs Frequencies Health Heart Rate Homeostasis Hyperemia Hypotension Hypovolemia Impaired cognition Impairment Lightheadedness Link Literature Lower Body Negative Pressure Measures Memory Memory Loss Methods Monitor Near-Infrared Spectroscopy Nerve Orthostasis Oxygen Patients Pattern Performance Pharmaceutical Preparations Phase Placebos Postural Orthostatic Tachycardia Syndrome Posture Recruitment Activity Reference Standards Reflex action Regulation Schools Short-Term Memory Supination Symptoms Systemic disease Tachycardia Task Performances Techniques Testing Visual Work aged counterregulation drug testing experimental study healthy volunteer heart rate variability hemodynamics improved neurovascular neurovascular coupling orthostatic intolerance prevent pyridostigmine reduce symptoms relating to nervous system respiratory response volunteer young woman

项目摘要

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.

项目概要/摘要姿势性心动过速综合征 (POTS) 是与过度运动相关的体位性不耐受的慢性形式直立性心动过速，主要发生于年轻女性（>85%）。头晕、疲劳和记忆力下降，通常被患者称为“脑雾”，与任务相关。神经血管耦合 (NVC) 将神经活动与 CBF 增加联系起来，称为“功能性充血”。尽管 POTS 中的记忆任务性能和 NVC 会随着倾斜角度的变化而恶化，但健康控制情况却并非如此，脑血流（CBF）仍然与对照相似，相反，我们观察到广泛的窄带低。 BP (OBP) 中的频率 (0.07-0.13 Hz) 振荡会夹带并放大 CBF (OCBF) 中的振荡。 OBP 和 OCBF 随着倾斜角度的增加而增加，导致工作记忆受损和功能降低心脏迷走神经压力反射将血压与心率结合起来以缓冲血压变化。在 POTS 中，心脏迷走神经压力感受性反射会因直立性逐渐受损，但在健康志愿者中则不会，并解释了 OBP、OCBF 和 NVC 的损失；进一步改善压力反射可降低 OBP、OCBF 和锅里的脑雾。我们将招募年龄为 15-30 岁（N=60）的女性 POTS 受试者，停止用药且没有其他全身性疾病我们的方法有三部分：1）我们将使用参考标准。改良牛津技术测量心迷走压力反射，并评估工作记忆和功能充血，而 POTS 和健康受试者则经历从仰卧到 60° 的分级直立倾斜，增量为 15°。我们预计 POTS 中低频时 OBP 和 OCBF 会逐步增加，同时逐步减少功能性充血和 N-Back 记忆任务的表现 2) 我们将外部强制 OBP 和 OCBF 使用振荡下半身负压来证明 OCBF 和功能性充血和 N-Back 记忆任务表现下降 3) 我们将比较急性使用上述方法 1) 的实验方法，比较地高辛和吡斯的明相对于安慰剂的效果。文献表明这些药物可增加心血管迷走神经压力反射并改善副交感神经张力疾病和健康；它们可以减少 POTS 中的心动过速和症状。 POTS 中心迷走神经压力反射受损与认知丧失之间存在联系，但可能适用于多种情况出现压力反射缺陷的循环系统疾病。