CHARACTERIZATION OF VASCULAR TONE ON LUNG FLUID BALANCE

这项研究计划的主要目的是测试 假设肺血管张力升高和肺损伤改变了 组胺能、胆碱能和肾上腺素能介导的肺 血管反应，例如肺毛细血管压力和 微血管通透性受到影响，从而破坏肺液 平衡 具体而言，该提案将：1）描述不同的 血管紧张度升高的模型 血管阻力-顺应性和微血管分布 磁导率 待测试的升高血管张力的模型包括 U46619（血栓烷类似物），内皮素-I（血管收缩肽）， 去甲肾上腺素和血管紧张素11 2)将响应与 组胺能、胆碱能和肾上腺素能受体的激活 正常血管张力下的系统，以及使用 上述模型和使用佛波醇肉豆蔻酸酯的肺损伤后 醋酸盐（PMA）输注、油酸输注和HCL气道滴注。 3)比较主动增加血管张力与被动增加血管张力的效果 当上述受体系统受到刺激时，血管扩张; 和4）评估当组胺能， 胆碱能和肾上腺素能受体系统在肺中被激活， 正常血管张力、升高的血管张力和损伤。 节段性 肺血管阻力和顺应性的分布将是 通过使用单独的动脉、静脉和双血管 闭塞技术。 肺微血管通透性将 通过测量毛细过滤系数来评价， 等重毛细管压力和渗透反射 系数 除了生理测量，表征 组胺能、胆碱能和肾上腺素能受体系统将 通过动力学速率常数测量进行快速评价， 通过测定血管活性介质的存在来进行生物化学测定。 的 被动血管扩张对这些受体介导效应的影响 将通过不同静水压灌注进行评估。 最后，在受体刺激后的肺血流模式将被 通过观察锌硫化镉化合物的分布来评价 （黄色荧光血管标记物）对照，血管色调，和 受伤的肺

The major objective of this research proposal is to test the hypothesis that elevated pulmonary vascular tone and lung injury alter the histaminergic, cholinergic, and adrenergic-mediated pulmonary vascular responses such that both pulmonary capillary pressure and microvascular permeability are affected, thereby disrupting lung fluid balance. Specifically, this proposal will: 1) characterize different models of elevated vascular tone with respect to the segmental distribution of vascular resistance-compliance, and microvascular permeability. The models of elevating vascular tone to be tested include U46619 (thromboxane analog), endothelin-I (vasoconstrictor peptide), norepinephrine, and angiotensin 11. 2) compare the responses to the activation of the histaminergic, cholinergic, and adrenergic receptor systems at normal vascular tone, and elevated vascular tone using the models outlined above, and following lung injury using phorbol myristate acetate (PMA) infusion, oleic acid infusion and HCL airway instillation. 3) compare the effect of active increases in vascular tone to passive vessel distention when the receptor systems stated above are stimulated; and 4) evaluate blood flow patterns that occur when the histaminergic, cholinergic, and adrenergic receptor systems are activated in lungs with normal vascular tone, elevated vascular tone, and injury. The segmental distribution of pulmonary vascular resistance and compliance will be determined by use of separate arterial, venous, and double vascular occlusion techniques. Pulmonary microvascular permeability will be evaluated by measurement of the capillary filtration coefficient, isogravimetric capillary pressure, and the osmotic reflection coefficient. In addition to physiological measurements, characterization of the histaminergic, cholinergic, and adrenergic receptor systems will be evaluated pharmacologically by kinetic rate-constant measurements and biochemically by assaying for the presence of vasoactive mediators. The effect of passive vessel distention on these receptor-mediated effects will be assessed by perfusion with different hydrostatic pressures. Finally, pulmonary blood flow patterns upon receptor stimulation will be evaluated by observing the distribution of zinc cadmium sulfide compound (a yellow fluorescing vascular marker) in control, vascular toned, and injured lungs.