Central Mechanisms of Respiratory Arrest

呼吸骤停的中枢机制

基本信息

批准号：
7228106
负责人：
Fadi Xu
金额：
$ 34.68万
依托单位：
LOVELACE BIOMEDICAL & ENVIRONMENTAL RESEARCH INSTITUTE
依托单位国家：
美国
项目类别：
财政年份：
2004
资助国家：
美国
起止时间：
2004-07-01 至 2009-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7228106
关键词：
Acids Acute Address Adenosine Altitude Sickness Apnea Asthma Breathing C Fiber Capsaicin Carotid Body Cavia Cell Nucleus Chemicals Chemoreceptors Condition Disease Edema Figs - dietary Functional disorder Generations Glutamates Goals Heart Atrium Hypercapnic respiratory failure Hypoxemia Hypoxia Infection Injection of therapeutic agent Injury Intercellular Fluid Irritants Lactic acid Life Lung Lung diseases Mediating Nerve Neurologic Neurons Neurotransmitters Pathologic Patients Peripheral Physiological Play Pneumonia Pulmonary Edema Rattus Reflex action Relative (related person)Reporting Research Personnel Respiration Respiration Disorders Right atrial structure Role Sensory Signal Transduction Site Sleep Structure Substance K Receptor Substance P Sudden infant death syndrome Synapses Testing Thinking Work afferent nerve airway inflammation carotid sinus concept insight interest nocturnal Hypoxemia novel pressure programs receptor relating to nervous system research study respiratory response

项目摘要

DESCRIPTION (provided by applicant): Bronchopulmonary C-fibers (PCFs) constitute the majority of afferent nerves arising from the lungs and airways and play a key role in respiratory control. Pulmonary inflammation and edema stimulate PCFs, and are frequently accompanied by hypoxemia. Hypoventilation and apnea are often observed in patients under these pathologic conditions and worsened or even fatal when transient nocturnal hypoxemia occurs in sleep. However, the pathophysiology of these respiratory disorders is unknown. PCF stimulation produces a brief apnea that is centrally mediated by releasing glutamate to act on AMPA receptors located in the vicinity of the commissural nucleus (cNTS). Coincidently, inspiration is elevated by activation of the carotid body (CB) chemo-receptors that also terminate in the cNTS and some of them synaptically converge on the neurons driven by PCFs. Information about the interaction between two sensory inputs with opposite effects on ventilatory drive converging in the same central structure is currently lacking. We recently reported that PCF stimulation during acute hypoxia produced a ventilatory arrest (VA), 16-fold longer than the apnea induced by PCF stimulation alone, providing first evidence to describe an interaction of PCF activation and hypoxia in the control of breathing. Exogenous Substance P administered in the cNTS prolongs PCF-mediated apnea by about 10-fold and CB stimulation promotes SP release in the cNTS. Therefore, to elucidate the neurologic mechanisms underlying the VA, we will address three fundamental questions in this proposal: (a) Does the VA require both inputs and the interaction occur peripherally and centrally? If so, what are their relative contributions? (b) Where does the central integration take place, and which neurotransmitters are involved? (c) Does the central interaction occur at PCF-driven neurons, and if so, how? Our study will provide a better understanding of central respiratory integration and the pathophysiology of respiratory disorders inherent in the diseases involving both hypoxemia and pulmonary inflammation/edema.

描述（由申请人提供）：支气管肺C纤维（PCF）构成由肺和气道引起的大多数传入神经，并在呼吸控制中起关键作用。肺部炎症和水肿刺激PCF，并且经常伴有低氧血症。在这些病理状况下，在患者中经常观察到过度衰减和呼吸暂停，当瞬时夜间低氧血症在睡眠中发生时，甚至致命。但是，这些呼吸系统疾病的病理生理尚不清楚。 PCF刺激会产生一个简短的呼吸暂停，该呼吸暂停是通过释放谷氨酸作用于位于合理核（CNTS）附近的AMPA受体作用的中心介导的。巧合的是，灵感通过激活颈动脉体（CB）化学受体的激活而提升，该化学疗法也终止在CNT中，其中一些是在PCF驱动的神经元上的突触收敛。目前缺乏有关两个感官输入之间对通气驱动器融合的相反影响的感觉输入之间相互作用的信息。我们最近报道说，急性缺氧期间的PCF刺激产生了通气停滞（VA），仅在PCF刺激中诱导的呼吸暂停长16倍，提供了第一个证据，以描述PCF激活和缺氧在控制呼吸方面的相互作用。在CNT中施用的外源物质P可将PCF介导的呼吸暂停延长约10倍，而CB刺激促进了CNT中的SP释放。因此，为了阐明VA的神经系统机制，我们将在此提案中解决三个基本问题：（a）VA是否需要投入，并且相互作用在周围和集中发生？如果是这样，他们的相对贡献是什么？（b）中央集成在哪里进行，涉及哪些神经递质？（c）中央相互作用是否发生在PCF驱动的神经元上，如果是，如何？我们的研究将更好地理解中枢呼吸道整合以及涉及低氧血症和肺部炎症/水肿的疾病固有的呼吸疾病的病理生理学。

项目成果

期刊论文数量（11）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Activation of opioid micro-receptors in medullary raphe depresses sighs.

中缝髓质中阿片类微受体的激活可抑制叹息。

DOI：
10.1152/ajpregu.90748.2008
发表时间：
2009
期刊：
American journal of physiology. Regulatory, integrative and comparative physiology
影响因子：
0
作者：
Zhang,Zhenxiong;Xu,Fadi;Zhang,Cancan;Liang,Xiaomin
通讯作者：
Liang,Xiaomin

Respiratory syncytial virus infection in anesthetized weanling rather than adult rats prolongs the apneic responses to right atrial injection of capsaicin.

与成年大鼠相比，麻醉断奶大鼠的呼吸道合胞病毒感染延长了右心房注射辣椒素的呼吸暂停反应。