MECHANICAL INTERDEPENDENCE IN THE DEVELOPING LUNG

形态计量学和功能研究表明， 哺乳动物在出生时就完全发育了，而实质组织和 血管在出生后继续发育。这项提案探索了 这种不同的增长模式对机械设备的影响 呼吸道、实质和肺血管系统的相互依赖 在麻醉羔羊的早期发育过程中。四个假设 将会受到考验。前三个假设与呼吸道有关- 实质上相互依赖：1)发展中的呼吸道是 特别容易受到尺寸变形的影响，因为 它们的本征塑性和产生的高径向应力 从肺实质中提取。2)材料的内在可塑性 航空公司是结构性成熟变化的结果 成分和肌肉张力。3)区域差异 成分和肌肉张力决定了人体的纵向差异 呼吸道对径向应力的尺寸反应。这些 地区差异受发展和病理因素的影响 州政府。为了检验这些假设，呼吸道尺寸将是 直接在支气管管型中进行定量和功能评估 根据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。 可调节呼吸道的呼吸道的固有特性 然后，我们将从发展的角度来审视相互依存 在健康和肺生长被改变后的观点 博莱霉素的给药。这些固有属性包括 迷走神经控制的支气管运动张力，支气管收缩， 以及气道壁的结构(胶原/弹性蛋白)成分。 第四个假设与血管实质有关。 相互依存。根据这一假设，不发达的人 胎儿和新生儿肺的血管床1在 存在血流增加，但不能进一步 血管招募。血管周围应力的松弛 血管扩张会降低血管的总弹性 当肺血流量增加时，肺的后座力。为了测试 这一假说，在体内的弹性反冲压，肺血 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(双指示剂稀释度)将在增加后测量 控制动静脉瘘的肺血流。这个 从这些研究中获得的信息将有助于澄清 发育中的呼吸道和肺血管对 机械和药物干预以及 病态的侮辱。因此，拟议的研究将提供 预防和识别呼吸道损伤的合理依据 危重新生儿，特别是那些需要机械治疗的新生儿 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.