CONTROL OF BREATHING IN NEWBORNS

虽然新生儿的呼吸调节有许多相似之处 成虫在数量和质量上存在差异。这是有可能的 这些发育差异解释了明显的 新生儿对延长的自发性呼吸暂停的易感性。这个 目前的研究是基于这样一种假设：中枢神经机制 在呼吸调节方面比传统上更重要 被认可了。长期目标是发展对 破坏呼吸动力稳定的中枢神经机制。这个 这项研究的具体目标是描述 中枢和外周对呼吸反应的化学感觉机制 新生儿的低氧血症。 一种实验动物模型已经被开发出来，可以消除这种影响 通常伴随着通风的改变而产生的化学负反馈 但它允许通过测量膈来量化呼吸输出 神经活动。提出了利用该模型进行的两项研究。这个 首次利用测量脑细胞外液pH、PCO2和C1- 评估中枢化学感觉刺激对呼吸的变化。我们的 初步结果表明，脑干区域负责 新生儿低氧血症期间化学感觉变碱性，但不是年龄较大者 动物。这第一个研究将描述机制的成熟。 通过检测脑干的变化，在缺氧期间改变ECF的pH值 ECF、二氧化碳分压、脑干血流量及不同药物的影响 抑制脑干缓冲能力。第二项研究利用了上述内容 模型来确定外周化学传感器的作用，特别是 颈动脉体部，有在刺激呼吸过程中的低氧血症 新生儿。特异地，颈动脉窦神经传入化学感觉活动 会量化低氧血症期间可能产生的抑制作用 将评估反馈机制和一种新的镇静剂。 中枢和外周化学感觉传入的相互作用 呼吸神经元的中枢网络是维持呼吸功能的关键 低氧血症时的呼吸。这种互动可能具有重要的 对有低氧风险的早产儿呼吸暂停的影响 脑损伤，大龄婴儿有猝死的风险 综合征，以及婴儿和成人阻塞性睡眠呼吸暂停 导致低氧血症。

Though respiratory regulation in newborns has many similarities with adults, quantitative and qualitative differences exist. It is possible that these developmental differences account for the pronounced susceptibility of newborn infants to have prolonged spontaneous apnea. The present studies are based on the hypothesis that central neural mechanisms are more important in respiratory regulation than traditionally recognized. The long-range objective is to develop an understanding of central neural mechanisms which destabilize respiratory drive. The specific objective of this study is to characterize the influence of central and peripheral chemosensory mechanisms on the respiratory response to hypoxemia in newborns. An experimental animal model has been developed which eliminates the effect of negative chemical feedback that usually follows a change in ventilation but which allows quantitation of respiratory output by measuring phrenic nerve activity. Two studies are proposed which utilize this model. The first utilizes measurement of brain extracellular fluid pH, PCO2, and C1- to assess change in central chemosensory stimulation to respiration. Our preliminary results indicate that the brainstem regions responsible for chemosensation become alkalotic during hypoxemia in newborn but not older animals. This first study will characterize the maturation of mechanisms by which ECF pH is altered during hypoxia by examining changes in brainstem ECF, PCO2, brainstem blood flow and the effects of various agents which inhibit brainstem buffering capacity. The second study utilizes the above model to determine the role that peripheral chemosensors, particularly the carotid body, have in stimulating respiration during hypoxemia of newborns. In specific, carotid sinus nerve afferent chemosensory activity will be quantified during hypoxemia and the effect of possible inhibitory feedback mechanisms and a new analeptic agent will be assessed. The interaction of central and peripheral chemosensory afferents on the central network of respiratory neurons is critical for maintenance of breathing during hypoxemia. This interaction may have important implications for premature newborns with apnea who are at risk for hypoxic cerebral damage, older infants at risk for the Sudden Infant Death Syndrome, as well as infants and adults with obstructive sleep apnea resulting in hypoxemia.