Respiratory failure is a major obstacle to recovery in severely injured patients. The long term goal of this research is to further understand the pathophysiologic processes involved in the development of post-traumatic acute lung injury (ALI). Lung injury will be studied using a murine hemorrhagic sock model as well as evaluating ALI in a two hit model. ALI will be characterized by light microscopy, wet-dry weight ratios, myeloperoxidase assay, changes in membrane permeability and most importantly lung function. Endothelial adhesion molecules play a pivotal role in the sequestration and activation of neutrophils in the lung following a variety of injuries. It is a goal to study the mechanism of neutrophil sequestration in the lung after hemorrhage and resuscitation and a second insult. The applicant will specifically evaluate the physiologic changes that occur in the mouse lung and the role of adhesion molecules and cytokines in his model of ALI. The central hypothesis is that hemorrhage and resuscitation result in increased expression of endothelial adhesion molecules in the lung, that these molecules lead to neutrophil sequestration and ALI, and that there are divergent mechanisms in the development of ALI after hemorrhage and infection. The knowledge gained from these studies could lead to potential treatments to decrease the morbidity and mortality from post-traumatic ALI.
| Claridge, Jeffrey A; Schulman, Andrew M; Young, Jeffrey S (2002) Improved resuscitation minimizes respiratory dysfunction and blunts interleukin-6 and nuclear factor-kappa B activation after traumatic hemorrhage. Crit Care Med 30:1815-9 |
| Claridge, J A; Weed, A C; Enelow, R et al. (2001) Laparotomy potentiates cytokine release and impairs pulmonary function after hemorrhage and resuscitation in mice. J Trauma 50:244-52 |
