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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）构成了来自肺部和气道的大部分传入神经，在呼吸控制中发挥着关键作用。肺部炎症和水肿会刺激 PCF，并经常伴有低氧血症。在这些病理条件下的患者中经常观察到通气不足和呼吸暂停，当睡眠中发生短暂的夜间低氧血症时，通气不足和呼吸暂停会恶化甚至致命。然而，这些呼吸系统疾病的病理生理学尚不清楚。 PCF 刺激会产生短暂的呼吸暂停，该呼吸暂停是通过释放谷氨酸作用于位于连合核 (cNTS) 附近的 AMPA 受体来集中介导的。巧合的是，颈动脉体 (CB) 化学受体的激活也会提高吸气的强度，这些受体也终止于 cNTS，其中一些突触会聚在由 PCF 驱动的神经元上。目前缺乏关于两个感觉输入之间相互作用的信息，这些感觉输入对汇聚在同一中央结构中的通气驱动产生相反的影响。我们最近报道，急性缺氧期间 PCF 刺激产生的通气停止 (VA)，比单独 PCF 刺激引起的呼吸暂停长 16 倍，为描述 PCF 激活和缺氧在呼吸控制中的相互作用提供了第一个证据。在 cNTS 中给予外源性物质 P 可使 PCF 介导的呼吸暂停延长约 10 倍，并且 CB 刺激可促进 cNTS 中 SP 的释放。因此，为了阐明 VA 背后的神经机制，我们将在本提案中解决三个基本问题：(a) VA 是否需要输入并且相互作用发生在外周和中枢？如果有，他们的相对贡献是什么？ (b) 中枢整合在哪里发生，涉及哪些神经递质？ (c) 中枢相互作用是否发生在 PCF 驱动的神经元上，如果是，是如何发生的？我们的研究将有助于更好地了解中枢呼吸整合以及涉及低氧血症和肺部炎症/水肿的疾病所固有的呼吸系统疾病的病理生理学。

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。