MODULATION OF BREATHING BY UPPER AIRWAY CHEMORECEPTORS

呼吸暂停在临床上很重要，因为它与严重呼吸暂停密切相关 神经缺陷和可能的突然原因不明死亡，其中一个原因 中枢性呼吸暂停，特别是在早产儿中，是对 通过不协调吞咽或反流引起的喉部化学反射 食物。在某些情况下，防御机制(如咳嗽、 吞咽)受损或不成熟，留下长期的威胁 呼吸暂停和发紫。尽管这种反射的潜在重要性， 人们对这种反射的中枢通路知之甚少。 或者是什么激活了重新启动呼吸的机制。我们的 初步结果表明，喉上神经(SLN) 刺激会导致周期性呼吸、缺氧和高碳酸血症， 持续整个刺激期。呼吸开始了 尽管他继续进行SLN刺激，这些呼吸是 与行为唤醒有关。这些呼吸可以用以下方法消除 亚手术剂量的麻醉药导致长时间的呼吸暂停、发紫 和心肺衰竭。 这项资助中提议的研究将利用喉感受器的激活来 回答几个问题；1)模型的敏感度是什么， 生理学的终末部位和继发性神经元效应 确定了喉感受器？2)呼吸暂停是通过什么机制发生的 终止包括肺传入、化学感受器和 生理上确定的呼吸神经元亚群？我们建议 通过1)测量通气量(气压)来回答这些问题 方法)、在喉部激活时的心率和血压 未麻醉完整和未麻醉去大脑仔猪的反射， 2)通过解剖追踪特定的通道来确定反射路径 中枢性传入和检测大鼠突触后的变化 刺激这些传入神经。轴突追踪是用辣根进行的 过氧化物酶转运与逆行刺激；突触后效应 通过呼吸相关神经元的细胞内记录进行研究 它们具有生理特征。这样做的预期结果是什么 工作将确定呼吸控制系统的哪些区域 在引起和终止中枢性呼吸暂停方面特别重要，因此 可能导致更好的治疗方式来治疗这些 婴儿会患上危及生命的呼吸暂停。

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.