CAROTID CHEMO/BARORECEPTORS ROLE IN APNEA AND HYPERPNEA

颈动脉化疗/压力感受器在呼吸暂停和呼吸过度中的作用

• 批准号: 6530667
• 负责人: CURTIS A SMITH
• 金额: $ 23.39万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-04-01 至 2004-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6530667
• 关键词: afferent nerve; baroreceptors; blood pressure; carbon dioxide; carotid body; cerebral ischemia /hypoxia; chemical stimulation; chemoreceptors; denervation; dogs; hypercapnia; hyperpnea; innervation; isolation perfusion; pulmonary respiration; respiratory hypoxia; sleep apnea; sympathetic nervous system

DESCRIPTION (Applicant's abstract): The long-term objective of this proposal is to understand the role of brain hypoxia in ventilatory and cardiovascular control. This is a crucial and controversial question, as it impinges upon both our fundamental understanding of how hypoxia affects central ventilatory and cardiovascular control systems and upon the pathophysiology of these control systems, particularly as they relate to sleep disordered breathing, hypertension, respiratory failure, and environmental hypoxia. To address this question adequately, we must also investigate fundamental questions about the physiology of the carotid body. Much of our knowledge about the integrative aspects of carotid body physiology may be based on animal and human models that were not appropriate to the problem. Accordingly, this proposal has 3 specific aims: 1) How does specific CNS hypoxia affect the control of ventilation and blood pressure? 2) What are the relative contributions of carotid body and central chemoreceptors to the ventilatory response to hypercapnia? 3) Is tonic carotid body afferent input important to the total system response to other stimuli? To accomplish these goals we will use a unique unanesthetized canine model that allows separation of the circulation to the carotid bodies from that of the rest of the systemic circulation so that peripheral and CNS responses can be studied separately in a neurally intact, unanesthetized preparation that can be studied during normal wakefulness and sleep. To date, we have used our unanesthetized carotid body perfusion to obtain preliminary data suggesting that specific CNS hypoxia stimulates breathing, and carotid body hyperoxia can reduce or eliminate the hyperventilatory response to CNS hypoxia. We also have preliminary data suggesting that carotid body denervation causes time-dependent changes in the CNS response to hypercapnia and thus may not be an appropriate model for studies designed to assess relative contributions of central and peripheral chemoreceptors.

描述（申请人摘要）：本申请的长期目标 建议是了解脑缺氧在通气和呼吸中的作用 心血管控制这是一个关键而又有争议的问题， 因为它影响了我们对缺氧 影响中枢神经系统和心血管控制系统， 这些控制系统的病理生理学，特别是当它们 与睡眠呼吸障碍、高血压、呼吸衰竭、 和环境缺氧。为了充分解决这个问题，我们必须 还调查了有关的生理学的基本问题， 颈动脉体我们对生物多样性综合方面的知识 颈动脉体生理学可以基于动物和人类模型， 不适合这个问题。因此，该提案有3 具体目标：1）特定的中枢神经系统缺氧如何影响对 通气和血压吗2)相对贡献是什么 颈动脉体和中枢化学感受器对兴奋性反应的反应 高碳酸血症吗3)紧张性颈动脉体传入输入对 系统对其他刺激的反应为了实现这些目标，我们 将使用一种独特的未麻醉的犬模型， 颈动脉体的循环与其他动脉体的循环不同， 体循环，以便可以研究外周和CNS反应 分别在一个神经完整的，未麻醉的准备， 在正常的清醒和睡眠状态下进行研究。到目前为止，我们已经使用我们的 未麻醉的颈动脉体灌注以获得初步数据 这表明特定的中枢神经系统缺氧刺激呼吸， 体内高氧可减少或消除对 中枢神经系统缺氧。我们也有初步数据表明颈动脉体 去神经支配引起CNS对以下事件的反应的时间依赖性变化： 因此可能不是研究的合适模型 旨在评估中枢和外周神经系统 化学感受器