VENTILATOR-INDUCED LUNG INJURY--MECHANISMS & PREVENTION

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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.