CENTRAL NEURONAL MECHANISMS--DECOMPENSATED HEMORRHAGE

轻度出血可引起自主神经和内分泌代偿 能够极大地减少低血压的反应。这些井- 已知的反应大多是由动脉卸载引起的 压力感受器，包括心脏迷走神经张力的退出和 强烈地激活交感神经流出。如果出血是 更严重的是，自主性补偿机制自相矛盾 颠倒了。出血的第二阶段或失代偿期 以心动过缓和交感神经急剧下降为特征 活性(失血性交感神经抑制。Hisi)生产 心血管进一步恶化。启动 失代偿期归因于迷走神经的激活 从心肺区传入的中枢通路 Hisi的数量尚不清楚。尽管如此，一些研究表明 中枢阿片肽可能在此病的发生中起关键作用 现象。拟议工作的目标是调查 参与出血的中枢神经回路部分 交感神经抑制和心动过缓。这项研究将分为 五个部分。 目的1：使用已建立的麻醉大鼠模型，我们将确定 HISI是否可以用放电率的降低来解释 延髓吻端腹外侧区的血管运动神经元。 目标2：我们将确定低血压出血是否激活 在RVLM内树枝状分布的GABA能神经元。我们还将确定 CVLM区域是否是HISI发生所必需的。 目标3：我们将确定低血压出血是否减少 中枢性呼吸驱动及其对HISI的影响 目的4：我们将确定阿片肽在体内的释放 RVLM助长了HISL 目标5：我们将确定哪些中枢神经系统神经元被激活 清醒大鼠的低血压出血以及它们是否 阿片能或伽马酸能。 了解神经生理学机制的触发 低血压出血应该会提高处理这一问题的能力 临床问题太频繁了。

Mild hemorrhage produces autonomic and endocrine compensatory responses that are able to greatly minimize hypotension. These well- known responses are mostly caused by unloading of arterial barorceptors and include withdrawal of cardiovagal tone and a vigorous activation of the sympathetic outflow. If hemorrhage is more severe the autonomic compensatory mechanisms are paradoxically reversed. This second or ~ decompensatory~ phase of hemorrhage is characterized by bradycardia and a sharp decrease of sympathetic activity ( hemorrhage-induced sympathoinhibiton. HiSI) that produce further cardiovascular deterioration. Initiation of the decompensatory phase has been attributed to the activation of vagal afferent from the cardiopulmonary region however the central pathways of HiSI are not known. Nevertheless several studies have suggested that CNS opiod peptides may play a key role in genesis of this phenomenon. The objective of the proposed work is to investigate the CNS portion of the circuitry involved in hemorrhage induced sympathoinhibition and bradyardia. The study will be divided into five parts. Aim 1: using an established anestheized rat model, we will determine whether HiSI can be explained by a reduction in the discharge rate of the vasomotor neurons of the rostral ventrolateral medulla. Aim 2: we will determine whether hypotensive hemorrhage activates CVLM GABAergic neurons that arborize in RVLM. We will also determine whether the CVLM region is necessary for HiSI to occur. Aim 3: we will determine whether hypotensive hemorrhage reduces central respiratory drive and whether this effect contributes to HiSI Aim 4: we will determine whether the release of opioid peptides in RVLM contributes to hiSl Aim 5: we will determine which CNS neurons are activated by hypotensive hemorrhage in conscious rats and whether they are opiodergic or GABAergic. Understanding the neurophysiological mechanisms triggered by hypotensive hemorrhage should lead to improved ability to manage this all too frequent clinical problem.