MATURATIONAL CHANGES IN THE PULMONARY MICROCIRCULATION

长期目标是定义 肺微循环。拟研究的具体领域 这一建议是：(A)纵向的成熟变化 肺血管压力的分布；(B)血管运动控制 对肺微循环的影响；及(C) 机械因素对肺微循环的影响。另一个领域 研究的重点将是确定慢性低氧对 机械性能和血管运动的成熟度 控制肺微循环。理由是 第一组研究将解释为什么 新生儿的液体积聚比成熟的肺更大，而且 为什么新生儿比成年人更容易发生 特定情况下的肺水肿(缺氧、肺 通货膨胀、肺血流量增加)。其他研究将 显示肺水平衡调节是如何被破坏的 新生儿心肺疾病的特点是 慢性缺氧。定义肺组织的成熟变化 微循环，将使用直接微穿刺术 测量离体、灌流肺的微血管压力 新生和成年动物。压力分别下降到每一个 血管节段将在控制下和以下情况下测量 实验条件：血流改变后，取出 血管舒张性紧张，暴露于低氧，输注5 羟色胺，在不同程度的肺膨胀和 左房压力。在另一系列单独的研究中， 微血管压力将在分离的肺中测量 暴露在低氧环境中的新生猪 2-7天。在这些研究中，微血管压力将是 在控制条件下测量，然后在更改 血液流动或暴露在低氧环境中。最后，为了确保 离体肺的微血管压力是相同的。 就像活着的新生儿的肺部一样，微血管压力 也将在麻醉的新生羔羊的肺中进行测量。这个 这些研究的结果应该有助于确定 在出生后肺发育期间的位置，改善我们的- 新生儿心肺疾病的病理生理学基础 并导致危重病人护理的改善 新生儿。

The long range objective is to define maturational changes in the pulmonary microcirculation. The specific areas to be studied in this proposal are: maturational changes in (a) the longitudinal distribution of pulmonary vascular pressures; (b) vasomotor control of the pulmonary microcirculation; and (c) the influence of mechanical factors on the pulmonary microcirculation. Another area of study will be to define the effect of chronic hypoxia on the maturation of the mechanical properties and vasomotor control of the pulmonary microcirculation. The rationale is that the first group of studies will explain why the tendency towards fluid accumulation is greater in newborn than in mature lungs and why newborns are more susceptible than adults to develop pulmonary edema under specific circumstances (hypoxia, lung inflation, increased pulmonary blood flow). The other studies will show how the regulation of lung fluid balance is disrupted in neonatal cardiopulmonary disorders that are characterized by chronic hypoxia. To define maturational changes in the pulmonary microcirculation, the direct micropuncture technique will be used to measure microvascular pressures in isolated, perfused lungs of newborn and adult animals. The pressure drops across each vascular segment will be measured under control and the following experimental conditions: after alteration of blood flow, removal of vasomotor tone, exposure to hypoxia, infusion of 5 hydroxytryptamine, and at different levels of lung inflation and left atrial pressure. In a separate series of studies, microvascular pressures will be measured in isolated lungs of newborn pigs that have been exposed to an hypoxic environment for 2-7 days. For these studies, microvascular pressures will be measured under control conditions and then after alteration of blood flow or during exposure to hypoxia. Finally, to ensure that microvascular pressures are the same in isolated lungs as they are in lungs of living newborns, microvascular pressures will also be measured in lungs of anesthetized newborn lambs. The results of these studies should help define the changes that take place during postnatal lung development, improve our under- standing of the pathophysiology of newborn cardiopulmonary disorders, and lead to improvements in the care of critically ill newborns.