Hyperpnea in Orthostatic Intolerance

直立性不耐受的呼吸过度

• 批准号: 7433672
• 负责人: JULIAN M STEWART
• 金额: $ 23.81万
• 依托单位: NEW YORK MEDICAL COLLEGE
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-04-01 至 2010-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7433672
• 关键词: Affect; Age; American; Baroreflex; Blood Circulation; Blood flow; Breathing; Carbon Dioxide; Carotid Body; Cerebral Hypoxia; Cerebrovascular Circulation; Cerebrum; Chemoreceptors; Chronic Orthostatic Intolerance; Data; Dizziness; Employment; Enrollment; Environmental air flow; Event; Exhibits; Fatigue; Functional disorder; Gender; Heart; Heart Rate; Hyperpnea; Hyperventilation; Hypocapnia; Investigation; Left; Lung; Measures; Methods; Muscle; Nerve; Oxygen; Patients; Peripheral; Rate; Relative (related person); Research; Respiration; Schools; Stress; Stretching; Symptoms; Syndrome; System; Tachycardia; Testing; Ultrasonography; Woman; base; electric impedance; peripheral blood; prevent; prospective; research study; respiratory; response; stretch reflex; vasoconstriction; volunteer

DESCRIPTION (provided by applicant): Chronic orthostatic intolerance takes the form of postural tachycardia syndrome (POTS) in many patients. POTS pathophysiology is heterogeneous but frequently related to increased sympathetic activation and often accompanied by hyperpnea without tachypnea. Cerebral blood flow is reduced by hypocapnia and systemic vasoregulation is also detrimentally affected. We hypothesize that excessive baroreflex unloading during orthostatic stress is the initiating event in POTS resulting in 1) reduced inhibition of chemoreceptor activity centrally and 2) stimulation of peripheral chemoreceptor activity due to sympathetically induced reductions in blood flow to the carotid body. Increased chemoreceptor activity leads to hyperpnea. We will test this hypothesis by comparing POTS patients with orthostatic hyperpnea (N=20) and without orthostatic hyperpnea (N=20), to healthy control subjects (N=15) asking the following research questions: 1) Is the respiratory chemoreflex function abnormal in POTS with hyperpnea and does it affect ventilation, sympathetic activity and baroreflex function differently compared to control subjects? 2) Does baroreflex unloading produce excessive sympathetic and chemoreflex activity, and pulmonary stretch response in POTS patients with hyperpnea compared to POTS patients without hyperpnea and to control subjects? 3) Does sympathetic stimulation unrelated to the baroreflexes affect chemoreflex sensitivity and sympathetic nerve activity in POTS? : To answer these questions we will enroll 40 subjects and 20 age and gender matched control subjects. Experiments will test whether hyperpnea is caused by sympathoexcitation initiated by baroreflex unloading, potentiated by chemoreflexes, and modulated by pulmonary stretch reflexes. Chemoreflex function curves for ventilation and muscle sympathetic nerve activity (MSNA, obtained by peroneal microneurography) will be measured during controlled changes in inhaled CO2 and oxygen. Interactive effects of chemoreceptors on baroreflexes, and baroreflexes on chemoreflexes will be assessed using MSNA, continuous BP assessment, pneumotachography, and measures of central blood flow using impedance methods, and ultrasound. The modified Oxford method will be used to intermittently assess the cardiovagal and sympathetic baroreflex, and will be supplemented by wavelet based continuous assessment of heart rate, BP, MSNA and peripheral blood flow. Hyperpnea and reduced cerebral blood flow is a severely debilitating and poorly tolerated finding in POTS. Prospective data will define the pathophysiological mechanisms involved in hyperpneic POTS in order to develop specific and effective therapy for the illness. Project Narrative Chronic orthostatic intolerance due to the postural tachycardia syndrome (POTS) affects over a million Americans, mostly young women, who are prevented from gainful employ or school attendance. While a rapid heart rate (tachycardia) is the hallmark of the illness, patients often develop hyperventilation and respiratory difficulty which remain unexplained. In the current proposal we will perform sophisticated tests of the circulation and respiration systems to study the causes, mechanisms and potential treatments of upright hyperventilation in POTS.

描述（由申请人提供）：许多患者的慢性直立性不耐受表现为体位性心动过速综合征（POTS）。POTS的病理生理学是异质性的，但通常与交感神经激活增加有关，并且通常伴有呼吸过度而不伴有呼吸急促。低碳酸血症会减少脑血流量，全身血管调节也会受到脑血管疾病的影响。我们假设直立性应激期间过度的压力反射卸载是POTS的起始事件，导致1）中枢化学感受器活动抑制减少和2）由于交感神经诱导的颈动脉体血流量减少而刺激外周化学感受器活动。化学感受器活性增加导致呼吸过度。我们将通过比较具有直立性呼吸过度（N=20）和不具有直立性呼吸过度（N=20）的POTS患者与健康对照受试者（N=15）来测试该假设，询问以下研究问题：1）具有呼吸过度的POTS中呼吸化学反射功能是否异常，以及与对照受试者相比，其是否不同地影响通气、交感神经活动和压力反射功能？2)与无呼吸过度的POTS患者和对照组相比，呼吸过度的POTS患者的压力反射卸载是否产生过度的交感神经和化学反射活动以及肺牵张反应？3)与压力反射无关的交感神经刺激是否影响POTS患者的化学反射敏感性和交感神经活动？为了回答这些问题，我们将招募40名受试者和20名年龄和性别匹配的对照受试者。实验将测试呼吸过度是否由压力反射卸载引发的交感神经兴奋引起，由化学反射增强，并由肺牵张反射调节。将在吸入CO2和氧气的受控变化期间测量通气和肌肉交感神经活动（MSNA，通过腓神经显微神经造影术获得）的化学反射功能曲线。将使用MSNA、连续BP评估、呼吸速度描记术和使用阻抗方法和超声测量中心血流来评估化学感受器对压力反射的相互作用以及压力反射对化学反射的相互作用。改良的Oxford方法将用于间歇性评估心迷走神经和交感神经压力反射，并将通过基于小波的心率、BP、MSNA和外周血流量连续评估进行补充。呼吸过度和脑血流量减少是POTS中严重衰弱和耐受性差的发现。前瞻性的数据将定义涉及呼吸过度POTS的病理生理机制，以开发针对该疾病的特异性和有效的治疗。由于姿势性心动过速综合征（POTS）引起的慢性直立不耐受影响了超过一百万的美国人，其中大多数是年轻女性，她们无法获得有报酬的工作或上学。虽然快速心率（心动过速）是疾病的标志，但患者通常会出现换气过度和呼吸困难，这些症状仍然无法解释。在目前的建议中，我们将进行复杂的循环和呼吸系统的测试，以研究的原因，机制和潜在的治疗直立过度通气的POTS。