MODULATION OF BREATHING BY UPPER AIRWAY CHEMORECEPTORS

呼吸暂停在临床上很重要，因为它与主要的 神经功能缺损和可能的不明原因的猝死， 中枢性呼吸暂停，特别是早产儿，是激活的 通过不协调吞咽或反流引起的喉化学反射 食物。 在某些情况下，防御机制（例如咳嗽， 吞咽）受损或不成熟， 呼吸暂停和发绀。 尽管这种反射的潜在重要性， 关于这种反射的中枢通路知之甚少， 传播或激活机制重新启动呼吸。 我们 初步结果表明，上级喉神经（SLN） 刺激引起周期性呼吸、缺氧和高碳酸血症， 在整个刺激期间持续。 开始呼吸 尽管SLN刺激持续，但这些呼吸 与行为唤起有关 这些呼吸可能会被消除， 亚手术剂量的麻醉剂导致长时间的呼吸暂停、发绀 和心肺衰竭 这项研究计划将使用喉感受器激活， 回答几个问题：1）模型的灵敏度是什么， 终止位点和次级神经元的影响，从生理 识别喉感受器？2)呼吸暂停是通过什么机制 包括肺传入神经、化学感受器和 生理上确定的呼吸神经元亚群？我们提出 为了回答这些问题，1）测量通风（气压 方法），心率和血压在喉的激活过程中， 在未麻醉的完整和未麻醉的去大脑仔猪中的反射， 2)通过解剖学追踪模式特异性来定义反射通路 传入神经中枢和检查突触后的变化引起的 刺激这些传入神经。 用辣根做轴突追踪 过氧化物酶转运和逆向刺激;突触后效应 通过呼吸相关神经元的细胞内记录来研究 其具有生理学特征。 预期的结果是， 工作将确定呼吸控制系统的区域， 在引起和终止中枢性呼吸暂停中特别重要， 可能会导致更好的治疗方式，在治疗这些 患有危及生命的呼吸暂停的婴儿。

Apnea is clinically important since it is strongly correlated with major neurologic deficits and possibly sudden unexplained death, One cause for central apnea, especially in the pre-term infant, is activation of the laryngeal chemoreflex through discoordinated swallowing or regurgitation of food. Under some conditions, defense mechanisms (e.g. coughing, swallowing) are impaired or immature leaving the threat of protracted apnea and cyanosis. Despite the potential importance of this reflex, little is known of the central pathway over which this reflex is propagated or what activates mechanisms to re-initiate breathing. Our preliminary results have shown that superior laryngeal nerve (SLN) stimulation induces periodic breathing, hypoxia and hypercapnia which lasts throughout the period of stimulation. Breaths are initiated despite the continuation of he SLN stimulus and these breaths are associated with behavioral arousal. These breaths may be eliminated with sub-surgical doses of anesthetics resulting in prolonged apneas, cyanosis and cardiorespiratory collapse. Studies proposed in this grant will use laryngeal receptor activation to answer several questions; 1) What are the model sensitivities, termination sites and secondary neuronal effects from physiologically identified laryngeal receptors? 2) By what mechanism is the apnea terminated including the roles of pulmonary afferents, chemoreceptors and physiologically identified subgroups of respiratory neurons? We propose to answer these questions by 1) measuring ventilation (barometric method), heart rate and blood pressure during activation of the laryngeal reflex in unanesthetized intact and unanesthetized decerebrate piglets, 2) defining the reflex pathway by anatomically tracing modal specific afferents centrally and examining the post-synaptic changes induced by stimulation of these afferents. Axonal tracing is done by horseradish peroxidase transport and antidromic stimulation; post-synaptic effects are studied by intracellular recording from respiratory related neurons which are physiologically characterized. The anticipated results of this work will identify the areas of the respiratory control system which are of particular importance in causing and terminating central apnea, and so may lead to better therapeutic modalities in the treatment of those infants subject to life threatening apneas.