MODULATION OF BREATHING BY UPPER AIRWAY CHEMORECEPTORS

儿童和成人年龄组中的呼吸暂停仍然是一种现象 人们对此知之甚少。然而，最近的证据表明，一个重要的 呼吸暂停发生的决定性因素是 外周呼吸传入神经。我们建议研究相互作用 上呼吸道化学感受性传入与新生儿呼吸的关系 以及心血管控制系统作为睡眠状态和年龄的函数。 因为麻醉和手术创伤可能会改变心肺功能 反应性，所有建议的研究都将在未麻醉的， 长期使用仪器的小猪。研究将集中在 刺激喉上神经传入。刺激将用于两个人 目的：1)作为对新生儿呼吸的特殊挑战，这需要 清除呼吸道和恢复呼吸的特异性反应，以及2)作为 用于以受控方式抑制呼吸系统的装置 为了检验神经调节剂和Hp之间的协同效应 呼吸道传入神经。我们的初步结果表明，电信号 非麻醉新生儿喉上神经的电刺激 仔猪导致严重的呼吸抑制、缺氧和 持续整个刺激期间的高碳酸血症(1小时)和 与动物的不适无关。我们建议研究 这种现象是通过测量通气量(气压法)、心脏 输出量和器官血流分布(微球)、心率和 心率变异性、血压(慢性插管)、耗氧量 (闭合系统)和SLN期间的上、下呼吸道阻力 不同年龄和早期睡眠状态的刺激。脑干 通过脑池内注射改变呼吸反应性 内啡肽和GABA激动剂和拮抗剂。化学感受器效应 通过改变周围氧气或二氧化碳的压力，静脉注射 少量的NaCN和外周化学神经支配。我们相信 这项工作将产生新的重要数据，以了解 新生儿呼吸暂停综合征，如睡眠呼吸暂停(原因不明的呼吸暂停)和上 可能导致心肺衰竭的呼吸道阻塞。这个 这项工作的预期结果很可能确定以下领域 呼吸系统，这对维持 在挑战中呼吸，因此最终可能导致药理学 靶向治疗和更好的治疗方法 婴儿容易患上一连串危及生命的呼吸暂停。

Apnea in the pediatric and adult age groups still remains a phenomenon that is poorly understood. However, recent evidence suggests that one important determinant factor in the generation of apnea is the activity level of peripheral respiratory afferents. We propose to study the interaction between upper airway chemoreceptive afferents and the neonatal respiratory and cardiovascular control systems as a function of sleep state and age. Because anesthesia and surgical trauma may alter cardio-respiratory responsiveness, all proposed studies will take place in unanesthetized, chronically instrumented piglets. Studies will center on the effects of stimulating superior laryngeal afferents. Stimulation will be used for two purposes: 1) as a specific challenge to neonatal breathing which demands a specific response to clear the airway and resume breathing, and 2) as a means for depressing the respiratory system in a controlled fashion in order to examine the synergistic effects between neuromodulators and upper airway afferents. Our preliminary results have shown that electrical stimulation of the superior laryngeal nerve in unanesthetized neonatal piglets leads to a profound depression of breathing, hypoxia and hypercapnia which lasts throughout the duration of stimulation (1 hour) and is not associated with discomfort to the animal. We propose to examine this phenomenon by measuring ventilation (barometric method), cardiac output and organ blood flow distribution (microspheres), heart rate and heart rate variability, blood pressure (chronic cannula), O2 consumption (closed system) and upper and lower airway resistance during SLN stimulation at various ages and sleep states in early life. Brainstem respiratory responsiveness will be altered through intracisternal injection of endorphins and GABA agonists and antagonists. Chemoreceptor effects will be discerned by changing ambient O2 or CO2 tension, venous injection of small amounts of NaCN and peripheral chemodenervation. We believe that this work will generate new and important data for the understanding of neonatal apnea syndromes such as sleep apnea (unexplained apnea) and upper airway obstruction that may lead to cardiorespiratory collapse. The anticipated results of this work will very likely identify those areas of the respiratory system which are of particular importance in sustaining breathing during challenge and so may ultimately lead to pharmacologic targeting and better therapeutic modalities in the treatment of those infants subject to bouts of life threatening apneas.