VENTILATOR-INDUCED LUNG INJURY--MECHANISMS & PREVENTION

已经确定，在未改变的肺中，通过大潮气量通气可以诱导肺损伤。 这种损伤在仰卧动物的依赖性肺区域中似乎更严重，并且通过应用呼气末正压（PEEP）而得到改善。 呼吸机诱导的肺损伤（VILI）的一个潜在机制是在呼吸周期（气道切应力）期间周围终末气道的周期性打开和关闭。 预防气道关闭的干预措施可能会预防这种现象，例如PEEP和俯卧位。 俯卧位时胸膜压梯度的降低提供了更均匀的通气分布，因此应减少呼气末有关闭风险的气道数量（与仰卧动物的依赖性肺区域相比），从而减少了由此产生的肺损伤量。方法：在不同潮气量、PEEP水平和姿势下，定量麻醉、瘫痪的新西兰白色家兔机械通气时肺损伤的严重程度和分布。将通过多种方法评估损伤严重程度，包括气体交换参数、呼吸力学、重量分析和定量形态测量学。具体目标：1）在不同的、随机分配的PEEP水平（0至10 cm H2O，以2 cm H2O为增量）下，定量用大VT通气的仰卧动物中每克无血干肺的组织学损伤和肺水的严重性和空间分布。2)在不同的随机分配的PEEP水平（0 - 10 cm H2O，增量为2 cm H2O）下，定量用大VT通气的俯卧动物中每克无血干肺的组织学损伤和肺水的严重程度和空间分布。 3)在没有PEEP的情况下，对以低VT（6至8 cc/kg）通气的仰卧动物的组织学损伤程度和每克无血干肺的肺水进行定量。4)使用N2洗脱曲线第III阶段的平均标准化斜率分析作为通气不均匀性的测量，确定PEEP和俯卧位对通气分布的影响。

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.