LUNG GROWTH AT HIGH ALTITUDE AND MAXIMAL O2 TRANSPORT

高海拔和最大氧气输送下的肺生长

基本信息

批准号：
6875029
负责人：
ROBERT LEE JOHNSON
金额：
$ 37.21万
依托单位：
UT SOUTHWESTERN MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
1996
资助国家：
美国
起止时间：
1996-06-01 至 2007-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6875029
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

项目摘要

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）：高空（HA）的人类本地人发展增加肺部体积和扩散能力与增强的肺泡一致生长并增加促进02转运的血液量。但是，其他适应HA（肺动脉肌肉的肌肉化，dissanaptic气道胸腔生长的生长和延迟）可能会损害O2的运输。这这些因素之间的相互作用在不同的高度处是不知道的。功能这些结构变化的后果只能在当血液体积可逆变化时，重新批准为海平面（SL）和肺血管反应性已经消退。我们采用这种方法解决狗中HA成熟的长期结构 - 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）气道生长滞后于HA的肺泡生长，导致通风分布不均，通气工作增加。 3）HA处的肺血管变化显着限制了最大心脏输出在SL。 4）HA的结构变化在重新升级为SL和SL和SL和对O2运输的影响，即持续的血管和气道影响异常抵消牙槽生长增强的益处。 5）增长胸腔的依赖程度受损。在极端高度受限的胸腔大小为肺部生长和O2转运设定了上限。我们计划将未成熟的狗（2个月）饲养到3时至3个月的躯体成熟度（12个月）与HA的水平（3，100m，3,800m或4,500m的分组）相比在SL处升高的控件。狗将在成熟时返回SL 休息和运动时的心肺测试，包括压力卷曲线，最大02吸收，气体交换效率和肺部扩散能力（DL）和肌肉，通气工作，血液动力学和血容量。方面气道，隔膜，肋骨，肺和脾脏将通过螺旋CT评估扫描。 DL的成分，间隔组织体积和肺血流将是定期测量，与血容量相关。 1年后。的重新成熟到SL，将重复研究以确定更改。在终端，将对详细的结构分析进行肺，呼吸道，机车和心室肌肉以及肋骨和肋骨长骨头。 Acini，Airways，Vasculator，胸腔的生长模式结构及其功能相关性将在3个级别上进行比较缺氧以确定O2转运中适应性的高度依赖性。