POSTNATAL MATURATION OF CARDIOVASCULAR REGULATORY SYSTEM

产后心血管调节系统的成熟

• 批准号: 2838890
• 负责人: PHYLLIS M GOOTMAN
• 金额: $ 29.27万
• 依托单位: SUNY DOWNSTATE MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 1978
• 资助国家: 美国
• 起止时间: 1978-08-01 至 2000-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2838890
• 关键词: brain stem transection; denervation; growth /development; heart function; infant animal; neural transmission; swine; sympathetic nervous system

DESCRIPTION: (Adapted from the Investigator's Abstract) Expression of coherence (i.e. correlated periodicities in neural signals) is known to appear in an age-related manner, and is taken as evidence of a neural oscillator. Coherence of sympathetic nerve discharge (SND) in developing swine will be explored using neurophysiologic and neuroanatomic techniques. The investigators will determine the validity of the following Hypotheses concerned with development of coherence of SND: specifically: 1) coherence of SND will show an age-related cephalo- caudal gradient with a pre-postganglionic lag, 2) coherence is a function of linkages of brainstem emergent networks, 3) baroreceptor and inspiratory network inputs are involved in the appearance of coherent periodicities, and 4) major sites of the brainstem CV regulatory system can be located through the use of transection of the neuraxis, and field and single neuron recordings. Knowledge of the proper sequence in the development of SND periodicities and the onset of coherence may be of clinical importance if lack of such coordinated activity fails to occur and prevents the neonate from responding to stresses in an integrated age-related pattern. These hypotheses will be tested in Saffan anesthetized piglets (less than 1 day - 3 months of age). The discharge of at least two sympathetic nerves (splanchnic, cervical sympathetic, peroneal, lumbar, renal) will be recorded simultaneously with phrenic activity (monitor of the respiratory pattern generator) and will include denervation of vagi and carotid sinus nerves and specific transections of the neuraxis including the spinal cord. Identification of the CV regulatory system will involve the following progression: a) determination of brainstem sites expressing Fos to baroreceptor/chemoreceptor manipulations, b) CV (heart rate, aortic pressure, regional arterial blood flows) and SND responses to chemical stimulation of the c-fos identified sites, c) phenotypic expression of neurons within these functionally identified regions. The rhythms in SND (1-2 Hz [respiratory modulated], 3-6 Hz (usually cardiac modulated) and 8-13 Hz ("10 Hz rhythm") will be used as markers for identification of neurons comprising- sympathetic brainstem circuits (by correlating population recording and single neuron activity to SND including the mathematical technique of partialization of power and coherence spectra to identify patterns of connectivity). Age- related changes will be identified by statistical analyses of results from the different age groups. The results of these studies should establish developmental changes in sympathetic periodicities as markers of postnatal maturity of the regulatory system and support the hypotheses concerning the importance of onset of coherence in SND as a major sign of postnatal maturation. The aforementioned experiments should help chose among the various explanations of sympathetic rhythmicity and help in the understanding of the most vulnerable period in the life of the child as well as define a possible mechanism in the etiology of SIDS.

描述：（改编自研究者摘要） 已知相干性（即神经信号中的相关周期性） 以年龄相关的方式出现，并被视为神经系统疾病的证据。 振荡器 交感神经放电（SND）的一致性 将使用神经生理学和 神经解剖学技术 调查人员将确定 以下假设与发展的连贯性有关， SND：具体而言：1）SND的一致性将显示与年龄相关的头- 尾侧梯度与节前节后滞后，2）连贯性是一个 脑干涌现网络的联系功能，3）压力感受器和 吸气网络输入参与了连贯的外观 周期性，以及4）脑干CV调节系统的主要部位 可以通过使用横断的神经轴定位， 和单神经元记录。 知识的正确顺序在 SND周期性的发展和相干性的开始可能是 如果没有发生这种协调活动，则具有临床重要性 并防止新生儿对压力作出反应， 年龄相关的模式。 这些假设将在Saffan中进行测试 麻醉仔猪（小于1天-3月龄）。 放电 至少两个交感神经（内脏，颈交感， 腓骨、腰椎、肾脏）将与膈神经同时记录 活动（呼吸模式发生器的监测器），并将包括 迷走神经和颈动脉窦神经的去神经支配和特定横断 包括脊髓在内的神经轴。CV的识别 监管制度将涉及以下进展：a） 确定脑干部位表达Fos， 压力感受器/化学感受器操作，B）CV（心率，主动脉 压力，局部动脉血流量）和SND对化学物质的反应 刺激c-fos识别位点，c）表型表达 神经元在这些功能识别区域内。 节奏在 SND（1-2 Hz [呼吸调制]，3-6 Hz（通常为心脏调制） 和8-13 Hz（“10 Hz节律”）将用作识别标记 包括交感脑干回路的神经元（通过相关 群体记录和单个神经元活动的SND，包括 功率谱和相干谱偏化的数学技术 以识别连接模式）。 与年龄有关的变化 通过对不同年龄组的结果进行统计分析确定 组 这些研究的结果应该建立发展 交感神经周期变化作为出生后成熟的标志 的监管制度，并支持有关的假设 SND中连贯性开始作为出生后主要体征的重要性 成熟 上述实验应该有助于选择 对交感神经节律的各种解释， 对儿童生命中最脆弱时期的理解， 以及确定小岛屿发展中国家病因学的可能机制。