CONTROL OF BREATHING IN NEWBORNS

尽管新生儿的呼吸调节与 成年人之间存在数量和质量上的差异。 可以 这些发育差异解释了 新生儿易患长时间自发性呼吸暂停。 的 目前的研究是基于这样的假设，即中枢神经机制 在呼吸调节中比传统的 认可. 长期目标是了解 中枢神经机制，使呼吸驱动不稳定。 的 本研究的具体目标是描述 呼吸反应的中枢和外周化学感受机制 新生儿低氧血症 已经开发出一种实验动物模型， 通常是在通风系统改变后产生的负化学反馈 但是其允许通过测量膈神经的呼吸输出来定量呼吸输出， 神经活动 两项研究提出了利用这个模型。 的 首先利用脑细胞外液pH、PCO 2和C1- 以评估中枢化学感觉刺激对呼吸的变化。 我们 初步结果表明，脑干区域负责 新生儿低氧血症时化学感觉异常，但老年人无 动物 第一项研究将描述机制的成熟 通过检测脑干的变化， ECF、PCO 2、脑干血流量和各种药物的作用， 抑制脑干缓冲能力。 第二项研究利用了上述 模型来确定外周化学传感器，特别是 颈动脉体，在低氧血症时有刺激呼吸作用 新生儿 具体来说，颈动脉窦神经传入化学感受活动 将在低氧血症期间定量， 将评估反馈机制和新的兴奋剂。 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对于维持 低氧血症时的呼吸 这种相互作用可能具有重要的 对有缺氧风险的呼吸暂停早产儿的影响 脑损伤，年龄较大的婴儿有婴儿猝死的风险 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.