MATURATIONAL CHANGES IN THE PULMONARY MICROCIRCULATION

长期目标是确定 肺微循环 研究的具体领域 这一建议是：（a）纵向的成熟变化 肺血管压力分布;（B）血管扩张控制 肺微循环;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缺氧对 机械性能和血管的成熟 肺微循环的控制。 基本原理是 第一组研究将解释为什么 新生儿肺中的液体积聚大于成熟肺中的液体积聚， 为什么新生儿比成年人更容易患上 特定情况下的肺水肿（缺氧、肺 膨胀，增加肺血流量）。 其他研究将 显示肺液体平衡的调节是如何被破坏的， 新生儿心肺疾病，其特征在于 慢性缺氧 为了确定肺部的成熟变化， 微循环，将使用直接微穿刺技术 在离体灌注的肺中测量微血管压力， 新生和成年动物。 每一层的压力都在下降 将在控制下测量血管节段， 实验条件：改变血流后，去除 血管紧张素，暴露于缺氧，输注5 羟色胺，并在不同水平的肺膨胀和 左心房压力 在另一系列研究中， 微血管压力将在离体肺中测量， 暴露于低氧环境中的新生猪， 2-7天 在这些研究中，微血管压力将 在控制条件下测量，然后在改变 血液流动或暴露于缺氧期间。 最后，为了确保 在离体肺中微血管压力是相同的 与新生儿肺中的情况一样， 还将在麻醉新生羔羊的肺中进行测量。 的 这些研究的结果应该有助于确定 在出生后肺部发育的地方，改善我们的下- 新生儿心肺功能障碍的病理生理学地位 疾病，并导致改善护理危重病 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.