DEVELOPMENT OF NEONATAL PULMONARY VASCULAR REACTIVITY

新生儿肺血管反应性的发展

• 批准号: 3472797
• 负责人: MARY L TOD
• 金额: $ 10.08万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-04-01 至 1995-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3472797
• 关键词: body water; eicosanoid metabolism; eicosanoids; fatty acid metabolism; growth /development; guinea pigs; hydrostatic pressure; hypoxia; infant animal; lung disorder; microscopy; newborn animals; pulmonary circulation; pulmonary edema; pulmonary hypertension; sheep; spectrometry; statistics /biometry; vascular endothelium; vascular endothelium permeability; vascular resistance; vasomotion

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.

这些研究将调查产后年龄对肺功能的影响 血管反应性、肺液平衡和内皮调节。 将特别强调与类二十烷酸的相互作用，因为 它们对于肺血流动力学的正常转变很重要 这发生在出生时。发育中的肺循环对 类二十烷酸将在三个年龄进行评估：0-4 天、12-16 天、2-3 天 羔羊 3 个月，豚鼠 0.3 个月（成年）。 对以下问题的回应 被确定的包括血管反应的强度和部位 类二十烷酸，其对新生儿肺液平衡的影响，以及 与年龄相关的血管反应性之间的潜在相互作用 类二十烷酸和肺血管内皮的调节。 该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与年龄的关系 离体灌注羔羊肺。 这些实验将阐明哪些 血管对血管活性类二十烷酸最敏感，以及它们如何 反应性因发育变化而改变。 回应将是 在常氧和缺氧期间测定，因为存在显着的 O 2 张力和肺血管张力和/或反应性的相互作用。 第二个具体目标是评估类二十烷酸对肺的影响 离体灌注羔羊发育期间的液体平衡 肺。 这些研究将试图确定以下方面的贡献： 静水压、血管表面积和血管通透性 类二十烷酸引起的肺水肿。 最终的具体目标是确定是否存在差异 内皮细胞对肺血管反应性的调节 到发展变化。 使用分离的肺内血管 豚鼠，第一个目标操作系统来确定对经典的反应 内皮依赖性和非内皮依赖性化合物作为年龄的函数。 这 这一具体目标的第二个目标是确定 内皮与类二十烷酸。