PERIPHERAL AND CENTRAL VENTILATORY CONTROL

本项目的第一个主要目标是检查 在长时间暴露于缺氧中起作用的控制机制， 也就是说，低氧驯化（VAH）， 恢复常氧后脱适应。 第二个主要目标 是为了更好地理解中枢-外周 呼吸控制中的化学感受器相互作用。 两 将使用实验方法：a）清醒的山羊颈动脉 身体（CB）灌注模型，允许分离和控制 到达CB的动脉血气与到达 B）单个化学感受器纤维传入的记录 麻醉山羊和犬CB的活性， 去脑犬 第一个具体目标是确定 在清醒的山羊中，减少CB处的刺激将产生VAH CB灌注模型和CB传入的时间依赖性增加 与稳态等二氧化碳-低氧时一样的活性 刺激. 第二个目标是确定哪些机制 有助于时间依赖性的，缺氧诱导的CB增加 在山羊中观察到的活性。 我们将测量传入CB活动 在山羊和狗中，在缺氧4小时之前、期间和之后， 回答这些问题：在缺氧时增加CB活性是一种 物种特有现象？ CB多巴胺耗竭或 对除缺氧外的CB刺激的反应性增加 贡献于此？ 麻醉或神经变性是否混淆 这些研究？ 我们还将启动CB单胺的研究 VAH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， 产生维持性换气过度（脱气） 在移除CB（或整个动物）缺氧时发生？ 这 上述研究将部分回答这个问题， 目标2. 我们还将使用清醒的山羊CB灌注模型， 研究中枢和外周化学感受器在 通过分别测量全身 高氧-高碳酸反应（中枢 化学感受器）和对CB高碳酸血症的缓解反应 在CB缺氧4 h诱导VAH前后。 第4 目的是利用独特的清醒山羊CB灌注模型， 研究中枢和外周之间的相互作用 化学感受器 该模型避免了两个主要问题， 麻醉和脑缺氧。 的解释性反应 全身动脉高氧-高碳酸血症（中枢化学感受器 刺激）将在三个水平的CB刺激下应用。 的 这些实验将提高我们对 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.