DYNAMICS OF ALVEOLAR RECRUITMENT IN LUNG INJURY

(根据申请人的摘要改编)候选人有以下背景 工程学的目标是使用这些技能来帮助解决临床问题 在学术重症监护环境中。广泛而长期的目标是 发展急症患者机械通气的改进策略 呼吸窘迫综合征(ARDS)以最大限度地增加气体交换和最大限度地减少 进一步的肺损伤。这些假设是：1)牙槽骨的发育过程 招募取决于空气-液体界面向下的传输 通向肺泡的气道，因此，对于相同的峰值压力，持续的 通货膨胀会招来比潮气呼吸更多的人口 关闭压力可以从一个数学模型唯一地确定 肺准静态压力-容量(PV)曲线，2B)一氧化氮气体摄取量 动力学，因为它与血红蛋白的反应时间很快，不应该 明显受肺毛细血管血容量的影响，因此 应跟踪肺泡重新募集的变化，3)ARDS是一种异质性 因此，招募的全球衡量标准可能不符合 招聘的当地衡量标准。具体目标是：1)定义 有效的持续通货膨胀招募策略的参数和 将这一动作与单独的窥视增加进行比较，2)确定 NO摄取动力学变化与预测人群的相关性 机械通气组的肺泡开放程度由肺活量曲线得出 3)比较招聘的全球衡量标准，如 3)比较招聘的全球衡量标准，如 肺力学和NO摄取动力学，使用正电子进行局部测量 发射断层扫描(PET)，包括区域性气体捕获、肺不张和 分流。该项目与健康的相关性在于它有可能提供 临床医生了解牙槽骨作用的工具和知识 在ARDS中招募并开始回答亲属的问题 补充量与低潮气量在保护肺功能方面的重要性 进一步的伤害。研究设计和方法利用了这两种动物 三个特定目标的实验和临床研究。 招聘将根据开放或关闭压力的分布情况进行评估 从肺活量曲线，一氧化氮摄取动力学，氧合和氦稀释肺 音量。对于SA1，不同的持续通胀策略将在 肺灌洗--识别受伤绵羊的一种动作特点 将成为后续议定书的标准。临床研究将 比较动物实验中的成功动作与呼气末正压增加 独自一人。SA2将根据以下情况比较解除保险的时间进程 根据肺泡关闭压力分布设置的PEEP水平 受试者在动物和患者中的PV曲线。SA3将比较本地 用全球招募指标衡量PET的招募情况 NO摄取动力学和肺力学。

(Adapted from applicant's abstract) The candidate has a background in engineering whose goal is to used those skills to help solve clinical problems in an academic critical care environment. The broad, long term objective is to develop improved strategies of mechanical ventilation in the acute respiratory distress syndrome (ARDS) to maximize gas exchange and minimize further lung injury. The hypotheses are: 1) the process of alveolar recruitment depends on the transmission of an air-liquid interface down the airway to the alveoli and therefore, for the same peak pressure, a sustained inflation will recruit more than tidal breaths, 2A) the population of opening and closing pressures can be uniquely determined from a mathematical model of the lung quasi-static pressure-volume (PV) curve, 2B) nitric oxide gas uptake kinetics, because of its rapid reaction time with hemoglobin, should not be significantly affected by pulmonary capillary blood volume and therefore should track changes in alveolar recruitment, and 3) ARDS is a heterogeneous syndrome, therefore, global measurements of recruitment may not correspond to local measurements of recruitment. The specific aims are: 1) to define the parameters of an effective sustained inflation recruitment maneuver and compare this maneuver to a PEEP increase alone, 2) to determine the correlation between changes in NO uptake kinetics and the predicted population of opened alveoli derived from the PV curve in the mechanically ventilated ARDS lung, and 3) to compare the global measurements of recruitment, such as ARDS lung, and 3) to compare the global measurements of recruitment, such as lung mechanics and NO uptake kinetics, with local measurements using positron emission tomography (PET) including regional gas trapping, atelectasis and shunt. The health relatedness of the project is in its potential to provide tools and knowledge for clinicians to understand the role of alveolar recruitment in ARDS and begin to answer the question of the relative importance of recruitment versus low tidal volumes in protecting the lung from further injury. The research design and methods utilize both animal experiments and clinical studies for each of the three specific aims. Recruitment will be assessed by distributions of opening or closing pressures from the PV curve, NO uptake kinetics, oxygenation, and helium dilution lung volume. For SA1, different sustained inflation maneuvers will be tested in lung lavage-injured sheep to identify the characteristics of a maneuver that will become the standard for the subsequent protocols. Clinical studies will compare the successful maneuvers from the animal experiments to PEEP increases alone. SA2 will compare the time course of derecruitment depending on the PEEP level set according to alveolar closing pressure distributions from the subject's PV curve in both animals and patients. SA3 will compare local measurements of recruitment by PET with the global measures of recruitment by NO uptake kinetics and lung mechanics.