LUNG GROWTH AT HIGH ALTITUDE AND MAXIMAL O2 TRANSPORT

高海拔和最大氧气输送下的肺生长

• 批准号: 6287953
• 负责人: ROBERT LEE JOHNSON
• 金额: $ 38.61万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-06-01 至 2006-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6287953
• 关键词: altitude; blood circulation; blood volume; cardiac output; dogs; environmental adaptation; growth /development; hemodynamics; hypoxia; lung; oxygen transport; pulmonary diffusion; pulmonary respiration; respiratory circulation; respiratory function; respiratory oxygen; respiratory oxygenation; vasomotion

DESCRIPTION (Applicant's abstract): Human natives of high altitude (HA) develop increased lung volume and diffusing capacity consistent with enhanced alveolar growth, and increase blood volumes that facilitate 02 transport. However, other adaptation to HA (muscularization of pulmonary arterioles, dysanaptic airway growth and retardation of thoracic growth) may impair O2 transport. The interplay among these factors at different altitudes is not known. Functional consequences of these structural changes can be isolated only after re-acclimatization to sea level (SL) when reversible changes in blood volume and pulmonary vascular reactivity have subsided. We employ this approach to address long-term structure-function relationships of maturation at HA in dogs. Hypotheses are 1) Hypoxia stimulates alveolar hyperplasia and enhances diffusive gas exchange. 2) Airway growth lags behind alveolar growth at HA, leading to uneven distribution of ventilation and increased ventilatory work. 3) Pulmonary vascular changes at HA significantly limits maximal cardiac output at SL. 4) Structural changes at HA persist after reacclimatization to SL and exert opposing effects on O2 transport, i.e., persistent vascular and airway abnormalities offset benefits derived from enhanced alveolar growth. 5) Growth of thorax is impaired in an altitude-dependent way; at extreme altitude, the restricted thoracic size sets an upper limit to lung growth and O2 transport. We plan to raise immature dogs (age 2 mo.) to somatic maturity (12 mo.) at 3 levels of HA (3, 100m, 3,800m or 4,500m in separate groups) compared with controls raised at SL. Dogs will be returned to SL at maturity for cardiopulmonary testing at rest and exercise, including pressure-volume curves, maximal 02 uptake, efficiency of gas exchange and diffusing capacity of lungs (DL) and muscles, ventilatory work, hemodynamics and blood volume. Dimensions of airways, diaphragm, rib cage, lungs and spleen will be assessed by spiral CT scan. Components of DL, septal tissue volume and pulmonary blood flow will be measured at regular intervals and correlated with blood volume. After 1 yr. of re-acclimatization to SL, studies will be repeated to determine regression of changes. Terminally, detailed structural analysis will be performed on the lungs, respiratory, locomotive and ventricular muscles, as well as ribs and long bones. Growth patterns of the acini, airways, vasculature, thoracic structures and their functional correlates will be compared at the 3 levels of hypoxia to determine the altitude-dependence of adaptation in O2 transport.

描述（申请人的摘要）：高海拔地区的人类（HA）发展 肺容量和弥散能力增加与肺泡增强一致 生长，并增加促进 02 运输的血量。然而，其他 对 HA 的适应（肺小动脉肌肉化、气道接触不良 生长和胸部生长迟缓）可能会损害氧气运输。这 这些因素在不同海拔高度之间的相互作用尚不清楚。功能性 这些结构变化的后果只能在之后才能被隔离 当血容量发生可逆变化时重新适应海平面（SL） 肺血管反应性已消退。我们采用这种方法来 解决狗 HA 成熟的长期结构与功能关系。 假设是 1) 缺氧刺激肺泡增生并增强 扩散气体交换。 2) HA处气道生长落后于肺泡生长， 导致通风分布不均，通气功增加。 3) HA处的肺血管变化显着限制了最大心输出量 在 SL。 4) 重新适应 SL 后，HA 的结构变化仍然存在 对 O2 运输产生相反的影响，即持续的血管和气道 异常抵消了肺泡生长增强带来的益处。 5）成长 胸部受损程度取决于海拔高度；在极端海拔处， 有限的胸部尺寸设定了肺部生长和氧气运输的上限。 我们计划将未成熟的狗（2 个月）饲养到 3 岁时身体成熟（12 个月） HA 水平（不同组中为 3、100m、3,800m 或 4,500m）与 控制在 SL 上调。狗将在成年后被送回 SL 休息和运动时的心肺测试，包括压力-容量曲线， 最大 O2 摄取、气体交换效率和肺扩散能力 (DL) 和肌肉、通气功、血流动力学和血容量。方面 将通过螺旋 CT 评估气道、膈肌、胸腔、肺和脾的情况 扫描。 DL、间隔组织体积和肺血流量的组成部分将是 定期测量并与血容量相关。 1年后。的 重新适应 SL，将重复研究以确定 SL 的回归 变化。最后，将进行详细的结构分析 肺、呼吸肌、运动肌和心室肌，以及肋骨和 长骨头。腺泡、气道、脉管系统、胸廓的生长模式 结构及其功能相关性将在 3 个级别进行比较 缺氧以确定 O2 运输适应的高度依赖性。