POSTNATAL MATURATION OF CARDIOVASCULAR REGULATORY SYSTEM

产后心血管调节系统的成熟

• 批准号: 6286270
• 负责人: Anthony Louis Sica
• 金额: $ 33.07万
• 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 2004-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6286270
• 关键词: age difference; brain mapping; cardiovascular function; denervation; developmental neurobiology; disease /disorder model; growth /development; hypercapnia; hypotension; infant animal; neural transmission; neuroregulation; phrenic nerve; respiration regulatory center; respiratory function; respiratory reflex; sudden infant death syndrome; swine; sympathetic nervous system

DESCRIPTION (Verbatim from the application): The overall goal of this proposal is to provide physiological and anatomical indices of maturation within neural networks involved in cardiorespiratory (CV-RESP) regulation. We shall focus on brainstem circuit neurons that mediate the CV-RESP responses to hypercapnic stress because: (a) this circuit plays an essential role in the maintenance of blood/gas homeostasis and (b) evidence suggesting that maladaptive responses to hypercapnic stimulation may be involved in the pathogenesis of Sudden Infant Death Syndrome (SIDS).The swine model of early development will be used to test the hypothesis that CV-RESP responses to prolonged hypercapnia are: (a) age-related, (b) modulated by peripheral afferent inputs, and (c) mediated by central a2-adrenoceptors. We also hypothesize that the network response to hypercapnia involves area postrema, nucleus tractus solitarii, and their synaptic targets within sympathetic (SYMP) control regions of the lateral medullary reticular formation. We shall test our hypothesis that catecholaminergic cell areas of the piglet medulla, previously shown to be activated by (a) CO2 and (b) hypotension, play crucial roles in the coordinated response. Of special significance are a subset of epinephrinergic neurons located in the SYMP premotor region of the rostral ventrolateral medulla. The effects of prolonged hypercapnia on SYMP outflow from at least two different segmental levels will be recorded, simultaneously with phrenic (PHR) activity. lEG expression will be quantitated with respect to age and brain stem sites. Age-related alterations in physiologic and neqronal responses to hypercapnia will be assessed following blockade of central alpha-2 receptors. Peripheral denervation will determine the importance of peripheral afferent inputs versus central effects ofhypercapnia at different ages. The correlation between lEG expression and SYMP-PHR outflows should reveal whether age-related changes in CV-RESP brain circuits (suggesting periods of vulnerability), are also observed in SYMP-PHR outflows; thus explaining the absence of a linear pattern of maturation of CV responses with stress. These studies should identify apparent dissociation between level of lEG expression (neuronal activation), SYMP coherence (regulatory outflow) and CV-RESP responses to stress (critical developmental period). The results should help in our understanding of the most vulnerable period in the life of the child and the pathogenesis ('window of opportunity') of SIDS.

描述(来自应用程序的逐字)：本提案的总体目标 是提供神经内成熟的生理和解剖指标 心脏呼吸调节网络(CV-RESP)。我们将重点放在 脑干环路神经元介导对高碳酸血症的CV-RESP反应 压力是因为：(A)这一回路在维持 血液/气体动态平衡和(B)证据表明，对 高二氧化碳刺激可能参与了婴儿猝死的发病机制 死亡综合征(SID)。将使用早期发育的猪模型来测试 持续高碳酸血症的CV-RESP反应的假设是：(A) 与年龄有关，(B)由外周传入信息调制，以及(C)由 中枢a2-肾上腺素受体。我们还假设网络对 高碳酸血症累及最后区、孤束核及其 外侧交感神经控制区内的突触靶点 延髓网状结构。我们将检验我们的假设 仔猪延髓儿茶酚胺能细胞区域，以前显示为 由(A)二氧化碳和(B)低血压激活，在协调的 回应。具有特殊意义的是肾上腺素能神经元的一个子集 位于延髓头端腹外侧的运动前运动区。这个 持续高碳酸血症对至少两个不同部位症状流出的影响 节段水平将被记录，与膈(PHR)活动同步。 腿部的表达将根据年龄和脑干部位进行量化。 高碳酸血症生理和神经反应的年龄相关性改变 将在阻断中枢α-2受体后进行评估。外围 去神经将决定外周传入输入的重要性与 不同年龄段高碳酸血症的中枢效应。两腿之间的相关性 表达和symp-PHR流出应该揭示年龄相关的变化 还观察到了CV-Resp脑回路(提示易损期) 在SYMP-PHR流出中；从而解释了为什么没有线性模式 应激条件下CV反应的成熟。这些研究应该确定明显的 腿表达水平(神经元激活)、症状之间的分离 一致性(调节流出)和CV-RESP对压力的反应(关键 发育期)。这些结果应该有助于我们理解大多数 儿童生命中的易损期及其发病机制 机遇‘)的影响。