VENTILATOR-INDUCED LUNG INJURY--MECHANISMS & PREVENTION

已经证实，大潮气量通气可在未改变的肺中引起肺损伤。这种损伤似乎在仰卧动物的依赖肺区域更严重，并通过呼气末正压（PEEP）的应用得到改善。呼吸机诱导的肺损伤（VILI）的一个潜在机制是呼吸循环期间终末气道的循环打开和关闭（气道剪切应力）。防止气道关闭的干预措施可能潜在地防止这种现象，如PEEP和俯卧位。俯卧位胸膜压力梯度的降低提供了更均匀的通气分布，因此应该减少末梢呼气时有关闭风险的气道数量（与仰卧动物的依赖肺区相比），从而减少由此导致的肺损伤。方法：在不同潮气量、PEEP水平和体位的机械通气条件下，量化麻醉、瘫痪新西兰大白兔肺损伤的严重程度和分布。损伤严重程度将通过几种方法进行评估，包括气体交换参数、呼吸力学、重量分析和定量形态计量学。具体目的：1)量化不同随机分配PEEP水平（0 ~ 10 cm H20，以2 cm H20为增量）下大VT通气仰卧动物的组织学损伤和每克无血干肺肺水的严重程度和空间分布。2)定量测定不同PEEP水平（0 ~ 10 cm H20，以2 cm H20为递增量）下，大VT通气俯卧动物的组织学损伤程度和每克无血干肺肺水的空间分布。3)定量测定低VT通气（6 ~ 8cc /kg）下仰卧动物无PEEP时的组织损伤程度和每克无血干肺肺水。4)确定PEEP和俯卧位对通气分布的影响，通过分析N2期冲洗曲线的平均归一化斜率作为通气不均匀性的度量。

It has been well established that lung injury can be induced in unaltered lungs by ventilation with large tidal volumes. This injury appears to be more severe in the dependent lung regions of supine animals and is ameliorated by the application of positive end expiratory pressure (PEEP). A potential mechanism responsible for ventilator-induced lung injury (VILI) is the cyclic opening and closing of terminal airways around during the respiratory cycle (airway shear stress). Interventions to prevent airways closure could potentially prevent this phenomenon, such as PEEP and prone position. Reduction in the pleural pressure gradient in the prone position provides more homogeneous distribution of ventilation and therefore should reduce the number of airways at risk for closure at end exhalation (compared with those in the dependent lung regions of supine animals) therefore reducing the amount of resultant lung injury. METHODS: Quantitate the severity and distribution of lung injury in anesthetized, paralyzed New Zealand white rabbits mechanically ventilated at varying tidal volumes , PEEP levels, and postures. Injury severity will be assessed by several methods, including gas exchange parameters, respiratory mechanics, gravimetric analysis and quantitative morphometrics. SPECIFIC AIMS: 1) Quantitate the severity and spatial distribution of histological damage and lung water per gram of blood-free dry lung in supine animals ventilated with large VT at different, randomly assigned, levels of PEEP (0 to 10 cm H20 in increments of 2 cm H20). 2) Quantitate the severity and spatial distribution of histological damage and lung water per gram of blood-free dry lung in prone animals ventilated with large VT at different, randomly assigned, levels of PEEP (0 to 10 cm H20 in increments of 2 cm H20). 3) Quantitate the degree of histological damage and lung water per gram of blood-free dry lung in supine animals ventilated at low VT (6 to 8 cc/kg) in the absence of PEEP. 4) Determine the effect of PEEP and prone position on the distribution of ventilation, using analysis of mean normalized slope of phase III of N2 washout curves as a measure of ventilation inhomogeneity.