VENTRAL MEDULLA, BREATHING, AND CENTRAL CHEMORECEPTION

我们认为SIDS是由延髓腹侧的异常引起的。 会干扰正常的保护性心肺反射。在这 我们将在两个发育阶段对仔猪进行实验性干扰 几次，人类弓状核的同源物被发现在 小岛屿发展中国家的受害者。这个同源基因被认为含有后梯形 核团(RTN)和丘脑旁区域、延髓中缝区域和 延髓尾侧腹外侧区的中央化学感受区。在……里面 成年动物，RTN/副穹隆和中缝区域的破坏 已知会减少呼吸输出量和对 对二氧化碳增加的呼吸反应。这次地震的大小 麻醉效果更好。外周化学感受器的去神经作用 放大了这种干扰对成年动物的有害影响； 当在脑干功能完整的新生动物身上进行实验时，它 导致换气不足、更频繁的呼吸暂停和死亡。我们将，在 具有和不具有完整颈动脉小体的去大脑仔猪，改变 微量注射1)兴奋性氨基的弓形同源功能 酸性神经毒素产生损伤，以及2)毒鼠碱和亲离子 谷氨酸激动剂/拮抗剂和促甲状腺激素释放激素。 基础状态下的膈神经输出量和血压及其影响因素 将测量对高碳酸血症和窒息的反应。在 含和不含完整颈动脉的非麻醉慢性仔猪制剂 身体，我们将检查弧形同源损伤对 自然清醒和睡眠等过程中的呼吸和血压 对高碳酸血症和窒息的反应。我们的目标是研究 弓状同源神经元和颈动脉小体输入的相对作用 无麻醉和自然状态下的呼吸和血压 睡眠和清醒。关于小岛屿发展中国家的三重风险模型 致病机制，我们是1)通过实验制造漏洞的方法 我们的皮损或注射，2)两个独立的发育年龄，以及 3)检查作为外源性压力的对高碳酸血症和窒息的反应 在有和没有颈动脉传入的情况下的觉醒和睡眠 尸体。

We proposed that SIDS results from abnormalities in the ventral medulla that interfere with normal protective cardiorespiratory reflexes. In this project we shall disrupt experimentally in piglets, at two developmental times, the homologue of the human arcuate nucleus found to be abnormal in SIDS victims. This homologue is proposed to contain the retrotrapezoid nucleus (RTN) and parapyramidal regions, the medullary raphe region, and the central chemoreceptor regions of the caudal ventrolateral medulla. In adult animals, disruption of the RTN/parapyramidal and raphe regions is known to diminish respiratory output and the sensitivity of the respiratory response to increased carbon dioxide. The magnitude of the effects is greater in anesthesia. Denervation of peripheral chemoreceptors magnifies the deleterious effects of this disruption in adult animals; when performed in newborn animals with intact brainstem function, it results in hypoventilation, more frequent apneas, and death. We shall, in the decerebrate piglet with and without intact carotid bodies, alter arcuate homologue function by microinjection of 1) an excitatory amino acid neurotoxin to produce lesions, and 2) muscarinic and ionotropic glutamate agonists/antagonists, and thyrotropin releasing-hormone. Phrenic nerve output and blood pressure in the baseline state and their responses to hypercapnia and asphyxia will be measured. In the unanesthetized chronic piglet preparations with and without intact carotid bodies, we will examine the effect of arcuate homologue lesions on breathing and blood pressure during natural wakefulness and sleep and on the responses to hypercapnia and asphyxia. Our goal is to examine the relative roles of arcuate homologue neurons and carotid body inputs on breathing and blood pressure in the absence of anesthesia and in natural sleep and wakefulness. In respect to the Triple Risk Model for SIDS pathogenesis, we are 1) experimentally creating a vulnerability by means of our lesions or injections, at 2) two separate developmental ages, and 3) examining, as exogenous stresses, responses to hypercapnia and asphyxia in wakefulness and sleep with and without afferent input from the carotid body.