Lung Contusion-Mechanisms and Interaction with Aspiration

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DESCRIPTION (provided by applicant): 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 to identify other factors that may be important in the pathogenesis of lung contusion with/without gastric aspiration. Animal research is complemented In Specific Aim # 3 by a observational, prospective study in blunt trauma patients with lung contusion . This epidemiological study wil also study the risk factors for unwitnessed gastric aspiration and examine other risk factors that may be associated with the progression of lung contusion to ALI/ARDS. 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.