Lung contusion affects 17%-25% of adult blunt trauma patients, and is the leading cause of death from blunt thoracic injury. A small animal model for isolated bilateral lung contusion has not been developed. We induced lung contusion in anesthetized rats by dropping a 0.3-kg weight onto a precordial protective shield to direct the impact force away from the heart and toward the lungs. Lung injury was characterized as a function of chest impact energy (1.8-2.7 J) by measurements of arterial oxygenation, bronchoalveolar lavage (BAL) albumin and cytology, pressure-volume mechanics, and histopathology. Histology confirmed bilateral lung contusion without substantial cardiac muscle trauma. Rats receiving 2.7 J of chest impact energy had 33% mortality that exceeded prospectively defined limits for sublethal injury. Hypoxemia in rats with maximal sublethal injury (2.45 J) met criteria for acute lung injury at < or =24 h, improving by 48 h. BAL albumin levels were highest at < or =24 h, and remained elevated along with increased BAL leukocytes and decreased lung volumes at 48 h. We concluded that an impact energy of 2.45 J induces isolated, bilateral lung contusion and provides a useful model for future mechanistic pathophysiological assessments.

Lung contusion is the leading cause of death from blunt thoracic trauma in adults, but its mechanistic pathophysiology remains unclear. This study uses a recently developed rat model to investigate the evolution of inflammation and injury in isolated lung contusion. Bilateral lung contusion with minimal cardiac trauma was induced in 54 anesthetized rats by dropping a 0.3-kg hollow cylindrical weight onto a precordial shield (impact energy, 2.45 Joules). Arterial oxygenation, pressure-volume (P-V) mechanics, histology, and levels of erythrocytes, leukocytes, albumin, and inflammatory mediators in bronchoalveolar lavage (BAL) were assessed at 8 min, at 4, 12, 24, and 48 h, and at 7 days after injury. The role of neutrophils in the evolution of inflammatory injury was also specifically studied by depleting these cells with intravenous vinblastine before lung contusion. Arterial oxygenation was severely reduced at 8 min to 24 h postcontusion, but became almost normal by 48 h. Levels of erythrocytes, leukocytes, and albumin in BAL were increased at

TNF-alpha is differentially manifested according to the components that make up the aspirate but the levels of TNF-alpha expression do not correlate with the severity of the resultant injury. However, the reduction in acid-induced lung injury by anti-TNF-alpha treatment indicates that TNF-alpha plays a role in the pathogenesis of aspiration pneumonitis.

Lung contusion (LC), commonly observed in patients with thoracic trauma is a leading risk factor for development of acute lung injury/ acute respiratory distress syndrome. Previously, we have shown that CC chemokine ligand (CCL)-2, a monotactic chemokine abundant in the lungs, is significantly elevated in LC. This study investigated the nature of protection afforded by CCL-2 in acute lung injury/acute respiratory distress syndrome during LC, using rats and CC chemokine receptor (CCR) 2 knockout (CCR2 2/2 ) mice. Rats injected with a polyclonal antibody to CCL-2 showed higher levels of albumin and IL-6 in the bronchoalveolar lavage and myeloperoxidase in the lung tissue after LC. Closed-chest bilateral LC demonstrated CCL-2 localization in alveolar macrophages (AMs) and epithelial cells. Subsequent experiments performed using a murine model of LC showed that the extent of injury, assessed by pulmonary compliance and albumin levels in the bronchoalveolar lavage, was higher in the CCR2 2/2 mice when compared with the wild-type (WT) mice. We also found increased release of IL-1b, IL-6, macrophage inflammatory protein-1, and keratinocyte chemoattractant, lower recruitment of AMs, and higher neutrophil infiltration and phagocytic activity in CCR2 2/2 mice at 24 hours. However, impaired phagocytic activity was observed at 48 hours compared with the WT. Production of CCL-2 and macrophage chemoattractant protein-5 was increased in the absence of CCR2, thus suggesting a negative feedback mechanism of regulation. Isolated AMs in the CCR2 2/2 mice showed a predominant M1 phenotype compared with the predominant M2 phenotype in WT mice. Taken together, the above results show that CCL-2 is functionally important in the down-modulation of injury and inflammation in LC.Keywords: lung contusion; macrophage chemoattractant protein-1; CC chemokine ligand-2; CC chemokine receptor 2; inflammation Thoracic injury is involved in nearly one-third of all acute trauma admissions (1-4), often including clinically significant lung contusion (LC) with subsequent respiratory deficits. LC is an important independent risk factor for the development of acute lung injury (ALI), acute respiratory distress syndrome (ARDS), and ventilator-associated pneumonia in affected patients (1-4), all of which are associated with high mortality and morbidity (5).The clinical pathophysiology of LC includes hypoxemia, hypercarbia, increased work of breathing, and decreased lung volumes and compliance in association with ventilation-perfusion mismatching, intrapulmonary shunting, edema, and segmental lung damage (1, 6, 7). As 30% of patients with LC progress to ALI/ ARDS (1), it is important to delineate the factors responsible for the development of progressive respiratory failure. Several lines of evidence suggest that factors in addition to traumainduced tissue damage may contribute to respiratory failure in LC (1, 3).Macrophage chemoattractant protein (MCP)-1/CC chemokine ligand (CCL)-2 is produced by a number of cells in response to inflammatory stimuli, suc...

Lung injury increases and bacterial clearance decreases in this experimental model of E. coli pneumonia following gastric aspiration. Cytokine profiles suggest possible mechanisms for the impaired antibacterial host defense.