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Lung transplantation has become a life-saving operation for patients with end-stage pulmonary disease, with a one-year survival of 80% and five-year survival of 60% noted in our own program. Initially, the early hazards of lung transplantation related to problems with bronchial healing, acute rejection, and infection. Most of these early problems have now been resolved. Airway anastamoses can be predictably done. Treatment of acute rejection episodes and prevention of infections such as cytomegalovirus have been well standardized with excellent results. Presently, the major cause of early mortality relates to post-transplant reperfusion injury. Originally it was thought this was purely a preservation injury, although it seemed odd that preservation would be an issue in lung transplantation due to the relative anatomic simplicity of the lung. The lung contains very little actual parenchyma, but has an interwoven lattice work of capillary endothelium and airway epithelium. It was quickly realized, however, that the majority of injury actually occurs during reperfusion. We now have a better understanding of these mechanisms and believe the major issue presently is the interaction of the inflammatory cascade with the pulmonary vascular endothelium during reperfusion. Since the major cause of early lung transplant mortality relates to reperfusion injury, we believe a better understanding of the pathophysiology of this entity and its treatment are critical.
Basic Science Model
In our lab, we utilize three models of pulmonary function following ischemia and reperfusion. These include: 1) an isolated, blood perfused, ventilated rabbit lung model, 2) a porcine left lung transplant model, and 3) an isolated, buffer-perfused, mouse lung model. Typically, we use our simpler isolated lung models for initial studies to help establish and screen specific investigations. Our in vivo porcine model is then used to confirm results found in the isolated lung model as well as to extend the period of reperfusion. The clinical relevance of any isolated organ preparation must continually be questioned; however, we have great experience with these models, and their use is well substantiated in the literature as methods tp study pulmonary function during reperfusion. In addition to these animal models, we also utilize an in vitro model to study the effects of hypoxia-reoxygenation on transformed and primary alveolar macrophages and type 2 epithelial cells.