MECHANICAL INTERDEPENDENCE IN THE DEVELOPING LUNG

形态和功能研究表明， 哺乳动物在出生时完全发育， 血管在出生后继续发育。 该提案探讨了 这种不同的生长模式对机械 气道、实质和肺血管的相互依赖性 在麻醉羔羊的早期发育过程中。 四个假言 会得到考验 前三个假设涉及气道- 实质相互依赖：1）发育中的气道 特别容易受到尺寸变形的影响， 它们的内在塑性和高径向应力 从肺实质中分离出来 2)的内在可塑性， 气道是结构成熟变化的结果， 成分和肌肉张力。 3)地区差异 组成和肌肉张力决定纵向差异， 气道对径向应力的尺寸响应。 这些 区域差异受发育和病理的影响， 状态 为了检验这些假设，气道尺寸将 直接在支气管铸型中定量， 从中心和外周气道阻力的测量 在不同的肺容量和不同的容量历史之后。 可能调节气道的气道固有特性 然后，从发展的角度审视相互依存关系 在健康和肺部生长被改变后， 博莱霉素的施用。 这些内在属性包括 迷走神经控制支气管张力，支气管收缩力， 和气道壁的结构（胶原/弹性蛋白）组成。 第四个假设涉及血管实质 相互依存 根据这一假设， 胎儿和新生儿肺的血管床1扩张， 血流量增加，但不能进一步 血管募集 血管周围应力的松弛 血管扩张产生的总弹性可能会降低 当肺血流量增加时肺的回缩。 测试 这一假设，在体内弹性回缩压力，肺血 血流量、血容量、毛细血管表面积（表观Vmax， 肺血管紧张素转换酶）和血管外肺 水（双倍指示剂稀释）将在增加后测量 肺血流量和可控的动静脉瘘。 的 从这些研究中获得的信息将有助于澄清 发育中的气道和肺血管对 机械和药物干预，以及 病态的侮辱 因此，拟议的研究将提供 预防和识别气道损伤的合理依据 在危重新生儿中，特别是那些需要机械 通风.

Morphometric and functional studies demonstrate that airways of mammals are completely developed at birth whereas parenchyma and vessels continue to develop after birth. This proposal explores the effect of this differential pattern of growth on the mechanical interdependence of airways, parenchyma, and pulmonary vasculature during early development in anesthetized lambs. Four hypotheses will be tested. The first three hypothesis concern airway- parenchymal interdependence: 1) Developing airways are particularly susceptible to dimensional deformation because of their intrinsic plasticity and the high radial stresses arising from the lung parenchyma. 2) The intrinsic plasticity of the airways is the result of maturational changes in structural composition and muscle tone. 3) Regional differences in composition and muscle tone determine longitudinal differences in the dimensional response of the airways to radial stress. These regional differences are influenced by development and pathological state. To test these hypotheses, airway dimensions will be quantified directly in bronchial casts and estimated functionally from measurements of central and peripheral airway resistance at various lung volumes and after different volume histories. Intrinsic properties of the airways that may modulate airway interdependence will then be examined from a developmental point of view both in health and after lung growth has been altered by administration of bleomycin. These intrinsic properties include vagal control of bronchomotor tone, bronchial contractility, and structural (collagen/elastin) composition of the airway wall. The fourth hypothesis concerns vascular-parenchymal interdependence. According to this hypothesis, the underdeveloped vascular bed 1 of the fetal and newborn lung dilates in the presence of increased blood flow but is not capable of further vascular recruitment. The relaxation of perivascular stress produced by vascular dilatation may decrease the total elastic recoil of the lung when pulmonary blood flow is increased. To test this hypothesis, in vivo elastic recoil pressure, pulmonary blood flow, blood volume, capillary surface area (apparent Vmax for pulmonary angiotensin-converting enzyme), and extravascular lung water (double indicator dilution) will be measured after increasing pulmonary blood flow with a controlled arteriovenous fistula. The information gained from these studies will help to clarify the response of the developing airways and pulmonary vessels to mechanical and pharmacological interventions as well as to pathological insults. The proposed research therefore will provide rational basis for the prevention and recognition of airway damage in critically ill newborns, particularly those requiring mechanical ventilation.