CAROTID CHEMO/BARORECEPTORS ROLE IN APNEA AND HYPERPNEA

描述(申请人摘要)：本项目的长期目标 建议了解脑缺氧在呼吸和呼吸中的作用 心血管控制。这是一个关键而有争议的问题， 因为它冲击了我们对缺氧的基本理解 影响中央通风和心血管控制系统 这些控制系统的病理生理学，特别是当它们 与睡眠呼吸紊乱，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 还研究了关于人的生理学的基本问题 颈动脉小体。我们的大部分知识都是关于 颈动脉体部生理学可以基于动物和人类模型 都不适合解决这个问题。因此，这项提案有3个 具体目标：1)特异性中枢低氧如何影响中枢神经系统的控制 通气量和血压？2)相对贡献是什么？ 颈动脉小体和中枢化学感受器对呼吸反应的影响 对于高碳酸血症？3)紧张性颈动脉小体传入输入对 系统对其他刺激的全部反应？为了实现这些目标，我们 将使用一种独特的非麻醉犬模型，允许分离 从颈动脉其他部位到颈动脉小体的循环 体循环，以便研究外周和中枢神经系统的反应 单独保存在神经完整的未麻醉制剂中，可以 在正常的清醒和睡眠状态下学习。到目前为止，我们使用了我们的 非麻醉颈动脉体灌注法获得初步数据 提示特定的中枢神经系统缺氧刺激呼吸，以及颈动脉 体内高氧可以减少或消除对 中枢神经系统缺氧。我们还有初步数据显示颈动脉小体 去神经支配导致中枢神经系统反应的时间依赖性变化 高碳酸血症，因此可能不是一个合适的研究模型 旨在评估中央和外围设备的相对贡献 化学感受器。

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.