Lung contusion is the commonest injury following blunt trauma to the chest that requires admission to the hospital. The pathogenesis and cellular mechansims of lung contusion are not well understood in part due to a lack of a reliable small animal model for isolated lung contusion . We have recently developed a reproducible rat model for isolated bilateral lung contusion from blunt trauma in a closed chest to facilitate mechanistic studies.This model is used here to examine the mechanistic inflammatory pathophysiology of lung contusion, as well as its interaction with gastric aspiration, a frequent occurence in trauma patients. Based on our preliminary studies, we hypothesize that acute inflammatory injury in isolated lung contusion resolves by 7 days. In the presence of an additional """"""""second hit""""""""such as gastric aspiration, this injury progresses to severe respiratory dysfunction (ALI/ARDS).
The Specific Aim #1 examines in detail the cellular mechanisms(role of neutrophils and alveolar macrophages) and specific chemokines(CINC-1, MIP-2 and MCP-1) in the rat model.
The Specific Aim # 2 studies the interaction of lung contusion with combination of acid and particulate aspiration injury to the lung in rats.
This aim examines the role of neutrophils, alveolar macrophages and chemokines (CINC-1, MIP-2 and MCP-1) in the interaction of these two insults. In addition, aim 2 uses genomic profiling (expression microarray complemented by quantitative RT-PCR) on whole lung homogenates to identify other pathways that may be important in the pathogenesis of lung contusion with/without gastric aspiration. Understanding lung contusion and its interaction with gastric aspiration, two common insults suffered by trauma patients, will greatly aid the development of new diagnostic and therapeutic modalities.
|Raghavendran, Krishnan; Davidson, Bruce A; Hutson, Alan D et al. (2009) Predictive modeling and inflammatory biomarkers in rats with lung contusion and gastric aspiration. J Trauma 67:1182-90|
|Raghavendran, Krishnan; Notter, Robert H; Davidson, Bruce A et al. (2009) Lung contusion: inflammatory mechanisms and interaction with other injuries. Shock 32:122-30|
|Raghavendran, Krishnan; Davidson, Bruce A; Huebschmann, John C et al. (2009) Superimposed gastric aspiration increases the severity of inflammation and permeability injury in a rat model of lung contusion. J Surg Res 155:273-82|
|Raghavendran, Krishnan; Davidson, Bruce A; Knight, Paul R et al. (2008) Surfactant dysfunction in lung contusion with and without superimposed gastric aspiration in a rat model. Shock 30:508-17|
|Raghavendran, Krishnan; Pryhuber, Gloria S; Chess, Patricia R et al. (2008) Pharmacotherapy of acute lung injury and acute respiratory distress syndrome. Curr Med Chem 15:1911-24|
|Raghavendran, Krishnan; Wang, Jiping; Belber, Christopher et al. (2007) Predictive value of sputum gram stain for the determination of appropriate antibiotic therapy in ventilator-associated pneumonia. J Trauma 62:1377-82;discussion 1382-3|