DEVELOPMENT OF NEONATAL PULMONARY VASCULAR REACTIVITY

这些研究将调查出生后年龄对肺部疾病的影响。 血管反应性、肺液平衡和内皮调节。 将特别强调与二十烷类化合物的相互作用，因为 它们对肺血流动力学的正常转换很重要。 这在出生时就会发生。发育中的肺循环对 二十烷类化合物将在三个日龄进行评估：0-4天，12-16天，2-3天 羔羊为0.3个月，豚鼠为0.3个月。对以下问题的回应 包括血管反应性的大小和位置 二十碳二碳酸酯及其对新生儿肺液平衡的影响 与年龄相关的血管反应性与 二十烷基类化合物和肺血管内皮细胞的调节。 这项建议的第一个具体目标是确定 肺血管对二十烷基类化合物的反应与年龄的关系 隔离灌流的羔羊肺。这些实验将阐明 血管对血管活性二十烷酸类化合物最敏感，以及它们的 反应性会因发育变化而改变。回应将是 在常氧和低氧期间测定，因为有显著的 O2张力与肺血管张力和/或反应性的相互作用。 第二个具体目标是评估二十碳二烯对肺的影响。 离体灌流羔羊这一发育期的液体平衡 肺部。这些研究将试图确定 静水压力、血管表面积和血管通透性 患有二十烷醇所致的肺水肿。 最终的具体目标将是确定是否存在差异 内皮细胞对肺血管反应性的调节作用 对发育变化的影响。使用分离的肺内血管 豚鼠，第一个目标是确定对经典的反应 内皮依赖和非内皮依赖的化合物作为年龄的函数。这个 这一具体目标的第二个将是确定 内皮细胞内含二十烷基硫酸酯。

These studies will investigate the effects of post-natal age on pulmonary vascular reactivity, lung fluid balance, and endothelial modulation. Particular emphasis will be placed on the interactions with eicosanoids, as they are important for the normal transition of pulmonary hemodynamics which occurs at birth. Responses of the developing pulmonary circulation to eicosanoids will be evaluated at three ages: 0-4 days, 12-16 days, 2-3 months for lambs and .3 months (adults) for guinea pigs. The responses to be determined included magnitude and site of vascular reactivity to eicosanoids, their effects on neonatal lung fluid balance, and the potential interaction between age-related vascular reactivity to eicosanoids and modulation by the pulmonary vascular endothelium. The first specific aim of this proposal is to determine the site of pulmonary vascular responses to eicosanoids as a function of age in isolated perfused lamb lungs. These experiments will elucidate which vessels are most responsive to vasoactive eicosanoids, and how their reactivity is altered by development changes. The responses will be determined during normoxia and during hypoxia, as there is a significant interaction of 02 tension and pulmonary vascular tone an d/or reactivity. The second specific aim is to evaluate the effects of eicosanoids on lung fluid balance during this developmental period in isolated perfused lamb lungs. These studies will attempt to determine the contributions of hydrostatic pressures, vascular surface area, and vascular permeability with eicosanoid-induced pulmonary edema. The final specific aim will be to determine whether there is a difference in the modulation of pulmonary vascular reactivity by the endothelium due to developmental changes. Using isolated intra-pulmonary vessels from guinea pigs, the first goal os to determine the responses to classic endothelium-dependent and -independent compounds as a function of age. The second of this specific aim will be to determine the interaction of the endothelium with eicosanoids.