Introduction: Activation and sequestration of leukocytes in the lung are thought to play a significant role in the development of Acute Lung Injury and ARDS. Clinical and laboratory studies have suggested that ventilation modalities that maintain functional residual capacity, prevent alveolar collapse and minimize cyclic overdistension are associated with better outcomes. We hypothesized that ventilation strategies that optimize lung recruitment would be associated with less inflammation and lung injury. The hypothesis was tested using a rabbit model of acute alveolitis.
Methods: Mature New Zealand White rabbits were anesthetized and instrumented with vascular catheters and a tracheostomy. Animals were assigned to receive partial liquid ventilation (PLV, n=15) with perflubron (Alliance Pharmaceutical Corporation), conventional mechanical ventilation (CMV, n=15) or high frequency oscillatory ventilation (HFOV, n=5) prior to administration of 0.9mg/kg of E. coli endotoxin IV. A group of uninjured animals supported with CMV served as controls (n=6). All animals were ventilated for 4.5 hours prior to sacrifice. The lungs were removed, inspected and cut in axial slices prior to preservation in formalin or snap freezing and storage at -70C. Myeloperoxidase activity (MPO), a marker of neutrophil accumulation, was measured in the supernatant of homogenized lung tissue by the method of Bradley using a spectrophotometric assay. Lung histology was assessed by light microscopy using a published lung injury score (range 0 to 28, directly proportional to severity). Severity of injury was scored based on alveolar and interstitial hemorrhage, alveolar and interstitial inflammation, edema, atelectasis and necrosis. A Kruskal-Wallis one-way Anova was used for comparisons between groups. The Dunn's method was used for post hoc pairwise multiple comparison. A p value < 0.05 was considered statistically significant.
