Considerable advancements have been made in the field of lung transplantation in recent years. Despite improvements, transplanted lungs remain vulnerable to ischemia-reperfusion injury. The inability to effectively transplant lung allografts in a manner that encourages immediate, optimal graft function persists as a major dilemma. The inflammatory system clearly has a role in ischemia-reperfusion injury, however, the specific cellular mediators are unclear. The majority of work in this field has focused on the recipient immune system. Resident alveolar macrophages from the donor, however, could be initiating reperfusion injury. Gadolinium chloride, a rare lanthanide earth element, inactivates macrophages. This compound has been used, along with dichloromethylene bisclodrinate, to inhibit alveolar macrophages in lung experiments involving adult respiratory distress syndrome (ARDS) and ozone induced injury. The objective of this research proposal is to investigate the importance of alveolar macrophages in the setting of lung ischemia-reperfusion. An isolated, blood perfused, ventilated rabbit lung model will be used as a small animal study in which the severity of lung injury during reperfusion can be accurately quantified and the functional consequences of donor macrophage inhibition with GdCI3 can be assessed. These findings will then be tested in a large animal study using a porcine left lung transplant model to explore macrophage inhibition in a more clinical setting of lung transplantation.
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