PERIPHERAL AND CENTRAL VENTILATORY CONTROL

这个项目的第一个主要目标是检查通风 长时间暴露在低氧环境中的控制机制， 即低氧呼吸习服(VAH)和 回到常氧后的脱习服。第二个主要目标 是为了更好地理解中枢-外周机制(S) 呼吸控制中的化学感受器相互作用。二 将使用实验方法：a)清醒的山羊颈动脉 身体(CB)灌流模型，允许分离和控制 到达脐动脉的动脉血气 B)单个化学感受器纤维传入的记录 麻醉山羊和狗的CB活性和 去掉狗的大脑。第一个具体目标是确定 减少对CB的刺激将在清醒的山羊中产生VAH CB灌流模型与CB传入的时间依赖性增加 稳态等碳低氧时发生的活动 刺激。第二个目标是确定什么机制 有助于时间依赖性的、低氧诱导的CB增加 在山羊身上观察到的活动。我们将测量传入CB的活动 在山羊和狗的低氧前、低氧期间和低氧4小时后 回答这些问题：在低氧期间增加CB活性是一种 物种特有现象？CB多巴胺是否耗尽或 提高对CB刺激的反应性，而不是缺氧 对此有贡献吗？麻醉或神经退行性变令人困惑吗？ 这些研究？我们还将启动对CB单胺的研究 血管紧张素转换酶的代谢。第三个目标是确定中央或 外周化学感受器机制或两者的组合， 产生维持性过度通风(脱气) 在去除CB(或整个动物)缺氧后发生的情况？这 上述研究将部分回答这一问题 目的2.我们还将使用清醒的山羊CB灌流模型 研究中枢和外周化学感受器在 通过单独测量系统的 高氧-高碳酸血症呼吸机能反应(中枢性 化学感受器)与慢性阻塞性肺疾病高碳酸血症的呼吸反应 CB缺氧4h诱导VAH前后的变化。第四辆 目的是利用独特的清醒山羊CB灌流模型 检查中枢和外围设备之间的相互作用 化学感受器。该模型避免了两个主要问题， 麻醉和脑缺氧。通气性反应 全身动脉高氧-高碳酸血症(中枢化学感受器 刺激)将应用于三个水平的CB刺激。这个 拟议的实验将提高我们对 低氧状态下的呼吸控制。

The first major goal of this project is to examine ventilatory control mechanisms operating in prolonged exposure to hypoxia, i.e., ventilatory acclimatization to hypoxia (VAH) and deacclimatization upon return to normoxia. A second major goal is to better understand mechanism(s) of central-peripheral chemoreceptor interaction in the control of breathing . Two experimental approaches will be used: a) the awake goat carotid body (CB) perfusion model which allows separation and control of arterial blood gases reaching the CB from those reaching the brain, and b) the recording of single chemoreceptor fiber afferent activity from the CB of anesthetized goats and dogs and decerebrate dogs. The 1st specific aim is to determine if diminishing stimuli at the CB will produce VAH in the awake goat CB perfusion model and time-dependent increase in CB afferent activity as occurs with steady-state isocapnic-hypoxic stimulation. A 2nd aim is to determine what mechanisms contribute to the time-dependent, hypoxia-induced increasing CB activity observed in goats. We will measure afferent CB activity in goats and dogs before, during and after 4 hours of hypoxia to answer these questions: Is increasing CB activity during hypoxia a species specific phenomenon? Does CB dopamine depletion or increased responsiveness to CB stimuli other than hypoxia contribute to it? Does anesthesia or nerve degeneration confound these studies? We will also initiate studies of CB monoamine metabolism in VAH. A 3rd aim is to determine if central or peripheral chemoreceptor mechanisms or a combination of both, produce the maintained hyperventilation (decclimatization) occurring upon removal of CB (or whole animal) hypoxia? This question will be answered in part by studies described above under aim 2. We will also use the awake goat CB perfusion model to examine the role of central and peripheral chemoreceptors in deacclimatization by measuring separately the systemic hyperoxic-hypercapnic ventilatory response (central chemoreceptors) and the ventilatory response to CB hypercapnia before and after VAH induced by 4 hours of CB hypoxia. A 4th aim is to utilize the unique awake goat CB perfusion model to examine the interaction between central and peripheral chemoreceptors. The model avoids two major problems, anesthesia and brain hypoxia. The ventilatory response to systemic arterial hyperoxic-hypercapnia (central chemoreceptor stimulation) will be applied at three levels of CB stimulation. The proposed experiments will improve our understanding of ventilatory control in hypoxic states.