VENTRAL MEDULLA, BREATHING, AND CENTRAL CHEMORECEPTION

我们认为SIDS是由腹侧髓质异常引起的 干扰正常的保护性心肺反射在这 我们将在仔猪中进行实验，在两个发育阶段， 次，人类弓状核的同源物被发现异常， 婴儿猝死综合症患者。这种同系物被建议包含逆梯形 核（RTN）和锥体旁区，髓缝区，和 尾侧延髓腹外侧的中央化学感受器区域。在 在成年动物中，RTN/锥体旁和中缝区域的破坏是 已知会减少呼吸输出和 呼吸系统对二氧化碳增加的反应的大小 麻醉效果更好。外周化学感受器去神经支配 放大了这种干扰对成年动物的有害影响; 当在具有完整脑干功能的新生动物中进行时， 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体的去大脑仔猪， 弓状同源物功能通过显微注射1）兴奋性氨基 酸性神经毒素产生病变，和2）毒蕈碱和离子型 谷氨酸激动剂/拮抗剂和促甲状腺激素释放激素。 膈神经输出量和血压在基线状态及其 将测量对高碳酸血症和窒息的反应。在 有和没有完整颈动脉的未麻醉慢性仔猪制剂 身体，我们将研究弓状同源病变的影响， 在自然清醒和睡眠期间的呼吸和血压 对高碳酸血症和窒息的反应我们的目标是检查 弓状同源神经元和颈动脉体输入对 呼吸和血压在没有麻醉和自然 睡眠和觉醒。关于小岛屿发展中国家三重风险模式 发病机制，我们是1）实验性地创造一个脆弱性， 我们的病变或注射，在2）两个不同的发展年龄，和 3)检查作为外源性应激的高碳酸血症和窒息反应 在有或没有颈动脉传入输入的清醒和睡眠中 身体

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.