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）：慢性体位不耐受采用许多患者的姿势心动过速综合征（POTS）的形式。 POTS病理生理学是异质性的，但经常与交感神经的增加有关，并且经常伴有无速度的肥大。脑血流量减少，而全身性血管调节也受到不利影响。我们假设在体位压力期间过度的压力反射卸载是在盆中的起始事件，导致1）降低了对化学感受器活性的抑制作用，而2）由于血液流动到Carotid身体的血液流量减少而刺激外周外化学感受器活性。化学感受器的活性增加导致厌倦。我们将通过比较具有体位高压症（n = 20）的POTS患者和无体位卧床（n = 20）与健康的对照受试者（n = 15）提出以下研究问题来检验这一假设：1）在患有肥大的盆中，与对照组受试者相比，它是否影响通气，交感神经活动和压力反射功能不同？ 2）与没有肥大性的POTS患者相比，肥大性患者的POTS患者的肉体交感神经和化学反射活性过多，以及肺部伸展运动反应？ 3）与压肢无关的交感神经刺激会影响盆中的化学反射灵敏度和交感神经活动吗？ ：要回答这些问题，我们将招募40名受试者和20岁的受试者以及性别匹配的控制科目。实验将测试蜂巢是否是由由压力反射卸载（通过化学反射剂增强）和肺拉伸反射调节的互惠兴趣引起的。在吸入的二氧化碳和氧气变化期间，将测量用于通气和肌肉交感神经活性的化学反射功能曲线。化学感受器对压力反射的交互作用以及对化学反射剂的互动效应将使用MSNA，连续的BP评估，肺炎造影术以及使用阻抗方法和超声检查进行中枢流动的测量评估。修改后的牛津法将用于间歇地评估心脏和交感的压力反射，并通过基于小波的基于小波的心率，BP，MSNA和外周血流动来补充。蜂巢和脑血流减少是一种严重的衰弱和耐受性的发现。前瞻性数据将定义肥大盆中涉及的病理生理机制，以开发特定有效的疾病治疗。由于姿势心动过速综合征（POTS），项目叙事叙事慢性体位不宽容会影响超过一百万的美国人，大多数是年轻妇女，这些妇女被阻止受到有酬工作或上学的待遇。虽然快速心率（心动过速）是疾病的标志，但患者经常会出现过度换气和呼吸困难，但仍无法解释。在当前的建议中，我们将对循环和呼吸系统进行复杂的测试，以研究盆中直立过度换气的原因，机制和潜在处理。