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.

项目摘要/摘要姿势心动过速综合征（POTS）是与过量相关的慢性形式心动过速，主要发生在年轻女性中（> 85％）。最令人不安的症状是头晕，疲劳和改善的记忆，通常被患者称为“脑雾”。与任务有关神经血管耦合（NVC）将神经活性活性与称为“功能性充血”的CBF增加。尽管记忆任务的性能和NVC用盆中的倾斜角度确定，但没有健康的对照，但脑血流（CBF）保持与对照相似。相反，我们观察到广泛的窄带低。在CBF（OCBF）中加入和放大振荡的BP（OBP）中的频率（0.07-0.13 Hz）。 OBP和OCBF随着倾斜角增加而增加，并导致工作记忆受损并降低功能充血。心脏伏击的Baroreflex夫妇BP到HR，以更改缓冲BP。我们假设心脏伏击的骨肉反射会逐渐受到盆中的正直的损害，但在健康的志愿者中没有障碍，和OBP，OCBF和NVC的损失；此外，改善BaroreFlex可以减少OBP，OCBF和大脑雾中的盆中。我们将招募15-30岁（n = 60）服药的女性花盆受试者，并且没有其他系统性疾病和健康受试者（n = 20）。我们的方法是三倍：1）我们将使用参考标准修改了牛津技术，以测量心脏的贝洛雷弗莱克体，并评估工作记忆和功能高血症虽然盆和健康受试者经历了从仰卧倾斜到60o in15o增量的坡度直立的倾斜度。我们预计在盆中低频下逐步增加了OBP和OCBF，逐步降低 N-BACK内存任务上的功能充血和性能2）我们将外部强制OBP和OCBF 使用振荡性下半身负压来证明OCBF和OCBF之间的因果关系 N-BACK内存任务上的功能充血和性能降低3）我们将比较急性地高辛和吡啶降含量的作用，使用上述方法的实验方法对安慰剂的影响。文献表明，这些药物会增加心脏的压力反射并改善副交感神经张力疾病和健康；它们可能会减少盆中的心动过速和症状。这项工作不仅会提供在盆中的心脏不利和认知损失之间的链接，但可能会发现潜水员的适用性循环系统疾病在其中定义出外观。