Distribution of mechanical energy intensity during mechanical ventilation: An investigation on the mechanisms of ventilator induced lung injury

机械通气需要设定肺扩张压力、潮气量、气道流量（或吸气呼气比）、呼吸速率和呼气末正压（PEEP）。所有这些变量共同构成了从呼吸机传递到呼吸系统的机械能。根据在肺部耗散的机械能的大小，可能会导致呼吸机诱发的肺损伤（VILI）。目前计算机械功率（即机械能随时间变化的量）的方法由于包含PEEP项而存在缺陷。另一方面，PEEP引起呼吸系统容积-压力曲线的移位，并导致静态应力-应变，这两者都是VILI的重要因素。此外，通常被忽视的是，VILI可能因肺部能量分布而有所不同，即所谓的能量强度。本申请中提出的两个项目旨在填补这一知识空白。第一个项目涉及在猪急性呼吸窘迫综合征（ARDS）的实验模型中，机械能量强度的创新概念及其在不同保护性机械通气设置下在肺部的分布。第二个项目在猪急性呼吸窘迫综合征的实验模型中研究了单独（无潮汐通气）和联合（有潮汐通气）PEEP对机械能强度和VILI的贡献，因此需要使用体外肺支持来获得适当的机械通气设置。这两个项目包括复杂的肺部成像技术的组合，允许确定区域肺力学和炎症，即计算机断层扫描（CT）和正电子发射断层扫描（PET）与18f -氟脱氧葡萄糖（18F-FDG，炎症标志物）动力学的数学模型。此外，将采用分子生物学和组织学技术对炎症和肺损伤进行最先进的测量。从理论上讲，通过解决机械功率计算中的不一致性，特别是通过将概念扩展到静态和动态能量以及静态和动态强度，可以得到全局和区域的VILI统一机制。此外，通过估算PEEP的能量贡献，可以决定性地改进机械通气时的肺保护策略。因此，这些研究结果将代表机械通气的基础科学和转化方面的实质性进展，对临床实践也有影响。

Mechanical ventilation requires the setting of lung distending pressures, tidal volume, airway flow (or inspiratory-to-expiratory ratio), respiratory rate and positive end-expiratory pressure (PEEP). Together, all those variables contribute to the mechanical energy that is transferred from the ventilator to the respiratory system. Depending upon the amount of mechanical energy that is dissipated in the lungs, ventilator-induced lung injury (VILI) may result. Current ways to calculate mechanical power, that is the amount of mechanical energy over time, are flawed due to inclusion of a PEEP term. On the other hand, PEEP causes a shift in the volume-pressure curve of the respiratory system, and results in static stress-and-strain, both of which contribute importantly to VILI. Also, it is usually neglected that VILI may differ regionally depending on the distribution of energy across lungs, so-called energy intensity. The two projects proposed in this application are intended to fulfill this gap in knowledge. The first project deals with the innovative concept of mechanical energy intensity and its distribution across the lungs at different protective mechanical ventilation settings in an experimental model of the acute respiratory distress syndrome (ARDS) in pigs. The second project addresses the isolated (without tidal ventilation) and the combined (with tidal ventilation) contribution of PEEP to mechanical energy intensity and VILI also in an experimental model of ARDS in pigs, whereby the use of extracorporeal lung support will be required to obtain the appropriate mechanical ventilation settings. Both projects include a combination of sophisticated lung imaging techniques that permit the determination of regional lung mechanics and inflammation, namely computed tomography (CT), and positron emission tomography (PET) with mathematical modeling of 18F-fluorodeoxyglucose (18F-FDG, inflammation marker) kinetics. In addition, state-of-the-art measurements of inflammation and lung damage using molecular biology and histology techniques will take place. Theoretically, by solving the inconsistencies in the computation of mechanical power, and specially by expanding the concept to static and dynamic energy as well as static and dynamic intensity, both globally and regionally, a unifying mechanism of VILI might result. Also, by estimating the contribution of the energy due to PEEP, strategies aiming at protecting lungs during mechanical ventilation could be decisively improved. Therefore, the results of these investigations would represent a substantial advance in basic science and translational aspects of mechanical ventilation, with impact on clinical practice as well.