DEVELOPMENT OF NEONATAL PULMONARY VASCULAR REACTIVITY

这些研究将调查出生后年龄对肺动脉高压的影响。 血管反应性、肺液体平衡和内皮调节。 特别强调的是与类花生酸的相互作用， 对肺血流动力学的正常转换有重要意义 这发生在出生时。发育中肺循环对 将在三个年龄评价类二十烷酸：0-4天、12-16天、2-3天 羔羊为0.3个月，豚鼠为0.3个月（成年）。 的答复 包括血管反应性的大小和部位， 类花生酸及其对新生儿肺液体平衡的影响， 年龄相关的血管反应性与 类花生酸和肺血管内皮的调节。 本提案的第一个具体目标是确定 肺血管对类二十烷酸的反应作为年龄的函数， 离体灌注羊肺。 这些实验将阐明 血管对血管活性类花生酸反应最强， 反应性随显影变化而改变。 这些答复将 在常氧和缺氧期间测定，因为存在显著的 O2张力和肺血管张力和/或反应性相互作用。 第二个具体目的是评估类二十烷酸对肺的影响。 液体平衡在此发育期间在隔离灌注羔羊 肺 这些研究将试图确定 静水压力、血管表面积和血管通透性 类花生酸引起的肺水肿 最终的具体目标是确定是否存在差异 在调节肺血管反应性的内皮细胞， 发展变化。 使用分离的肺内血管 豚鼠，第一个目标是确定对经典 内皮依赖性和非依赖性化合物作为年龄的函数。 的 第二个具体目标是确定 内皮细胞与类花生酸。

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.