The long range goal of the proposed study is to facilitate successful lung transplantation by improving methods for lung preservation and improving early lung function following transplantation. Achievement of these goals would facilitate the logistics of organ retrieval and improve utilization of the current donor pool. Furthermore improved early graft function would reduce morbidity and mortality following lung transplantation. The research plan has two components: 1) To characterize alterations occurring in the lung during preservation with specific reference to vascular endothelium. This will involve analysis of functional changes (measurement of permeability) and alterations of vascular endothelial cell surface proteins (intercellular adhesion molecules) which play a role in leukocyte-mediated injury following reperfusion. 2) To explore the use of specific strategies to reduce or eliminate leukocyte-endothelial interactions following reperfusion. These interventions include the use of monoclonal antibodies against adhesion molecules; pharmacologic inhibition of neutrophil activation and cytokine release; and use of monoclonal antibodies directed against tumor necrosis factor, a cytokine which plays a major role in leukocyte-mediated injury.
Showing the most recent 10 out of 59 publications
