CENTRAL NEURONAL MECHANISMS--DECOMPENSATED HEMORRHAGE

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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.