DYNAMICS OF ALVEOLAR RECRUITMENT IN LUNG INJURY

肺损伤时肺泡复张的动态

• 批准号: 6254823
• 负责人: ROBERT SCOTT HARRIS
• 金额: $ 13万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-03-01 至 2006-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6254823
• 关键词: adolescence (12-20); adult human (21+); adult respiratory distress syndrome; biomechanics; blood volume; capillary; chemical kinetics; elasticity; human subject; lung alveolus; lung injury; mathematical model; nitric oxide; patient oriented research; positive pressure breathing; positron emission tomography; pulmonary circulation; respirators; respiratory airway pressure; respiratory airway volume; respiratory function; sheep

(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.

（摘自申请人摘要）候选人有以下背景： 其目标是利用这些技能来帮助解决临床问题 在学术重症监护环境中。 长远的目标是 制定急性呼吸衰竭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， 进一步的肺损伤。 假设：1）肺泡上皮细胞的 补充取决于空气-液体界面向下的传输， 因此，对于相同的峰值压力， 通货膨胀将招募超过潮汐呼吸，2A）人口开放 和关闭压力可以从以下数学模型唯一地确定： 肺准静态压力-容积（PV）曲线，2B）一氧化氮气体摄取 动力学，由于其与血红蛋白的快速反应时间，不应被 显著受肺毛细血管血容量的影响，因此 应跟踪肺泡复张的变化，3）ARDS是一种异质性 综合征，因此，招募的全球测量可能不符合 招聘的地方措施。 具体目标是：1）确定 有效持续充气复张策略的参数， 将该操作与单独的PEEP增加进行比较，2）以确定 NO吸收动力学变化与预测人口之间的相关性 根据机械通气中的PV曲线得出的开放肺泡的 ARDS肺，以及3）比较募集的总体测量，例如 ARDS肺，以及3）比较募集的总体测量，例如 肺力学和NO摄取动力学，使用正电子 发射断层扫描（PET），包括局部气体捕获、肺不张和 分流。 该项目的健康相关性在于其提供 临床医生了解牙槽骨的作用的工具和知识 招募ARDS患者，并开始回答相关问题， 肺复张与低潮气量在保护肺免受 进一步的伤害。 研究设计和方法利用动物 针对这三个具体目标中的每一个进行实验和临床研究。 将通过打开或关闭压力的分布来评估招募 根据PV曲线、NO摄取动力学、氧合和氦稀释肺 音量. 对于SA 1，将在 肺灌洗损伤羊，以确定一个演习的特点， 将成为后续协议的标准。 临床研究将 将动物实验的成功操作与PEEP增加进行比较， 一个人 SA 2将根据以下因素比较去募集的时间过程： PEEP水平根据肺泡关闭压力分布设置， 动物和患者中受试者的PV曲线。 SA 3将比较本地 采用全球征聘措施， NO摄取动力学和肺力学。