NEUROGENIC INFLUENCES ON LUNG FLUID AND SOLUTE EXCHANGE

α-肾上腺素能刺激不依赖于血流动力学变化和急性 肺血管性高血压被假定为 肺水肿的发展后，各种临床综合征，如 如蛛网膜下腔出血、颅内高压、脑痉挛、 儿茶酚胺超载和高海拔暴露 相对于 过量的α肾上腺素能可能具有增加渗透性的作用 刺激，β肾上腺素能激动剂，如异丙肾上腺素或特布他林 减轻各种药物在外周产生的水肿 肺血管床 建议拨款的目的是 双重：1）确定神经源性介导的发病机制 肺水肿和2）以确定拟议的机制 β-激动剂药物的“抗水肿”作用。 具体方案将 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将产生 通过枕大池注射柠檬酸钠麻醉犬; 2）急性 肺血管性高血压将在麻醉的狗中产生， 左心房压力机械性升高; 3）不同程度的 将在孤立的左下动脉中诱导动脉和/或静脉高血压。 犬的肺叶（方案2和3将作为对照， 血管性高血压本身的影响）;和4）建议 渗透性增加和降低的影响， β-肾上腺素能刺激，分别将在培养的 肺动脉内皮细胞单层和清醒绵羊。 改变 将通过测量来评估经血管液体和蛋白质通量 淋巴液流量、淋巴液和血浆蛋白浓度， 反射系数和血管外肺水， 离体犬左心室毛细血管滤过系数的测定 下叶，并通过测量125 I-白蛋白清除培养的 内皮细胞单层。 肺组织形态学改变 神经源性介导的内皮细胞、结缔组织和上皮细胞 肺水肿将被表征并与 病理生理异常 关键的结构-功能关系， 使血管的振幅和持续时间相关， 高血压反应与肺部病理改变程度有关。

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.