Airway sensory nerves and dyspnea in human subjects

人类受试者的气道感觉神经和呼吸困难

基本信息

批准号：
6718422
负责人：
NAUSHERWAN K BURKI
金额：
$ 14.5万
依托单位：
UNIVERSITY OF CONNECTICUT SCH OF MED/DNT
依托单位国家：
美国
项目类别：
财政年份：
2002
资助国家：
美国
起止时间：
2002-02-01 至 2005-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6718422
关键词：
C fiber adenosine carotid body drug adverse effect drug screening /evaluation dyspneas human subject human therapy evaluation lidocaine nociceptors oxygen therapy patient oriented research receptor sensitivity respiratory disorder chemotherapy respiratory reflex sensory signal detection theophylline

项目摘要

DESCRIPTION (provided by applicant): Dyspnea, an unpleasant sensation of difficulty in breathing, is a common symptom in patients with cardiopulmonary diseases, but the underlying mechanisms are unclear. Amongst the various neural pathways, unmyelinated vagal C fibers arising from the lungs and airways have been implicated. The long-term objectives are to increase understanding of the mechanisms of dyspnea and specifically the role of pulmonary C fibers. Adenosine is a commonly used therapeutic intravenous drug for treatment of supraventricular tachycardia; it has been frequently reported to cause dyspnea. Recent studies from our laboratory reported the first evidence showing that adenosine stimulates pulmonary C fiber receptors in anesthetized rats. Preliminary human studies from our laboratory indicate that intravenous adenosine causes dyspnea and increase ventilation, and neither affect is associated with bronchoconstriction. Adenosine is known to increase ventilation by stimulating the carotid body chemoreceptors; such reflex stimulation would increase central motor command and could lead to the development of dyspnea. Our hypothesis is that adenosine causes dyspnea by direct activation of pulmonary C fiber, and it is not an indirect effect related to the increase in ventilation. The specific aims of the proposed study are: 1) to determine the latency and magnitude of dyspneic response, change in airway resistance, and ventilatory response to intravenous injection of adenosine in normal subjects and stable asthmatics; 2) to evaluate the effects of pretreatment with theophylline, and adenosine receptor antagonist, on the intensity of dyspnea and the ventilatory effects of intravenous adenosine; 3) to examine whether directly blocking pulmonary C fibers with inhaled lidocaine abolishes the sensation of dyspnea induced by adenosine in these subjects/patients; 4) to investigate if pretreatment with 100 percent O2, by reducing carotid chemoreceptor sensitivity, alters the dyspnogenic and ventilatory effects of intravenous adenosine. These studies should bring a better understanding of the underlying mechanism of adenosine-induced dyspnea and the role of bronchopulmonary C fibers.

描述（由申请人提供）：呼吸困难，一种令人不愉快的感觉呼吸困难是心肺患者的常见症状疾病，但基本机制尚不清楚。在各种神经中途径，由肺和气道产生的无髓的迷走神经纤维具有被暗示。长期目标是增加对呼吸困难的机制，特别是肺C纤维的作用。腺苷是一种常用的治疗性静脉药，用于治疗室外心动过速；经常据报道会引起呼吸困难。我们实验室的最新研究报告了第一个证据，表明腺苷刺激麻醉大鼠中的肺C纤维受体。我们实验室的初步人类研究表明静脉注射腺苷会引起呼吸困难并增加通风，并且两者都不是与支气管收缩有关。已知腺苷会增加通风通过刺激颈动脉体化学感受器；这种反射刺激将增加中央运动命令，并可能导致呼吸困难的发展。我们的假设是腺苷通过直接激活引起呼吸困难肺C纤维，这与增加的间接效果通风。拟议研究的具体目的是：1）确定呼吸困难反应的潜伏期和幅度，气道阻力的变化和对正常受试者静脉注射腺苷的通气反应和稳定的哮喘患者； 2）评估预处理的影响茶碱和腺苷受体拮抗剂在呼吸困难的强度上以及静脉注射腺苷的通气作用； 3）检查是否用吸入的利多卡因直接阻止肺C纤维废除这些受试者/患者腺苷引起的呼吸困难的感觉； 4）到通过减少颈动脉来调查100％O2预处理化学感受器敏感性，改变了呼吸困难和通气作用静脉注射腺苷。这些研究应该更好地了解腺苷引起的呼吸困难的基本机制和支气管肺C纤维。