NEUROGENIC INFLUENCES ON LUNG FLUID AND SOLUTE EXCHANGE

非血流动力学改变的α-肾上腺素能刺激和急性 肺血管高压被认为是高血压的发病机制。 在出现各种临床症状后发展为肺水肿 如蛛网膜下腔出血，颅内高压，脑性癫痫， 儿茶酚胺过量，以及暴露在高海拔地区。与之相对的是 过量α-肾上腺素能可能的通透性增加作用 刺激，β肾上腺素能激动剂，如异丙肾上腺素或特布他林 减轻各种因素在外周和外周引起的浮肿 肺血管床。建议拨款的目的是 两个方面：1)确定神经原性介导的发病机制 2)确定肺水肿的发病机制。 β-受体激动剂的“抗水肿”作用。具体的协议将 利用四种不同的实验模型：1)大量的α-肾上腺素能 刺激和急性肺血管高压会在 枕大池注射柠檬酸钠麻醉犬；2)急性 麻醉犬肺血管高压可通过 左房压力机械性升高；3)不同程度 孤立性左下动脉和/或静脉性高血压 狗的肺叶(方案2和3将作为对 血管高血压本身的影响)；以及4)建议的 α-和α-的增渗和降渗作用 β-肾上腺素能刺激将分别在培养的 肺动脉内皮细胞单层和清醒绵羊。改建 将通过测量来评估经血管内液体和蛋白质的流量 淋巴流量，淋巴和血浆蛋白浓度，蛋白质 反射系数和完整动物的血管外肺水，通过 犬左离体毛细管滤过系数的测定 下叶，并通过测定培养的~(125)I-白蛋白清除 内皮细胞单层。肺组织的形态改变 神经源性介导的内皮、间质和上皮 肺水肿将被表征并与 病理生理异常。关键结构-功能关系 是将血管的幅度和持续时间联系起来 高血压反应与肺部病理程度有关。

Alpha-adrenergic stimulation independent of hemodynamic changes and acute pulmonary vascular hypertension have been postulated as mechanisms in the development of pulmonary edema after a variety of clinical syndromes such as subarachnoid hemorrhage, intracranial hypertension, cerebral seizures, catecholamine overload, and exposure to high altitudes. In contrast to the possible permeability-increasing effects of excessive alpha-adrenergic stimulation, beta adrenergic agonists such as isoproterenol or terbutaline attenuate the edema that various agents can produce in peripheral and pulmonary vascular beds. The objectives of the proposed grant are two-fold: 1) to determine the pathogenesis of the neurogenic mediated pulmonary edema and 2) to determine the mechanism for the proposed "anti-edema" effect of beta-agonistic drugs. The specific protocols will utilize four different experimental models: 1) massive alpha-adrenergic stimulation and acute pulmonary vascular hypertension will be produced in anesthetized dogs by a cisterna magna injection of sodium citrate; 2) acute pulmonary vascular hypertension will be produced in anesthetized dogs by mechanical elevation of left atrial pressure; 3) varying degrees of arterial and/or venous hypertension will be induced in isolated left lower lung lobes of dogs (Protocols 2 and 3 will serve as controls for the effects of vascular hypertension per se); and 4) the proposed permeability-increasing and decreasing effects of alpha- and beta-adrenergic stimulation, respectively, will be studied in cultured pulmonary artery endothelial cell monolayers and awake sheep. Alterations in transvascular fluid and protein fluxes will be assessed by measurement of lymph flow, lymph and plasma protein concentrations, the protein reflection coefficient, and extravascular lung water in intact animals, by measurement of the capillary filtration coefficient in isolated dog left lower lobes, and by measurement of 125I-albumin clearance in cultured endothelial cell monolayers. Morphologic alterations of the pulmonary endothelium, interstitium, and epithelium elicited by neurogenic mediated pulmonary edema will be characterized and correlated with the pathophysiologic abnormalities. A key structure - function relationship to be made is to correlate the amplitude and duration of the vascular hypertensive response with the degree of pulmonary pathology.