CENTRAL NEURONAL MECHANISMS--DECOMPENSATED HEMORRHAGE

轻度出血产生自主神经和内分泌代偿 能够极大地减少低血压的反应。 这些好- 已知的反应主要由动脉的卸载引起 压力感受器，包括心迷走神经张力的撤回和 交感神经流出的剧烈激活。 如果出血是 自主代偿机制越严重， 颠倒了 出血的第二或失代偿期是 以心动过缓和交感神经系统的急剧减少为特征 活性（血管紧张素诱导的交感神经兴奋。 HiSI）， 心血管恶化。 启动 失代偿期归因于迷走神经的激活， 来自心肺区域的传入，然而中枢通路 HiSI是未知的。 然而，一些研究表明， CNS阿片肽可能在这一过程中起关键作用， 现象 拟议工作的目标是调查 涉及出血诱导的中枢神经系统部分 交感神经抑制和心动过缓。 研究将分为 五个部分。 目的1：利用建立的麻醉大鼠模型，我们将确定 HiSI是否可以通过放电率的降低来解释， 延髓头端腹外侧区的血管神经元。 目的2：我们将确定是否会激活肿胀性出血 CVLM GABA能神经元在RVLM中分支。 我们还将确定 CVLM区域是否是HiSI发生所必需的。 目的3：我们将确定是否肿胀出血减少 中枢呼吸驱动以及这种效应是否有助于HiSI 目的4：我们将确定阿片肽的释放是否在 RVLM有助于hiSl 目的5：我们将确定哪些CNS神经元被激活， 清醒大鼠的脑出血，以及它们是否 阿片能或GABA能。 了解由神经刺激引发的神经生理机制 肿胀性出血应导致管理此的能力提高 常见的临床问题。

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.