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Rapid reperfusion may be injurious to the ischemic lung. Our aim was to confirm that slow reperfusion improves postischemic pulmonary function and to elucidate the ultrastructural changes associated with slow versus rapid reperfusion.We used an ex vivo perfused rat lung transplant model to study the effect of slow versus rapid reperfusion on subsequent lung function and morphologic condition. Functional assessment was performed in (1) fresh lung, slowly reperfused; (2) fresh lung, rapidly reperfused; (3) ischemic lung (4 hours at 22°C), slowly reperfused; and (4) ischemic lung, rapidly reperfused.In group 4, the shunt fraction (P = .001), airway pressure (P = .001), and wet/dry ratio (P = .01) were significantly higher than in groups 1 through 3. Light and electron microscopy of slowly reperfused ischemic lungs (n = 4) appeared normal. Rapidly reperfused ischemic lungs (n = 4) demonstrated massive alveolar edema, hemorrhage, and epithelial "blebbing" by light microscopy. Electron microscopy identified the blebbing as separation of the epithelial layer from an intact basement membrane by edema fluid. The epithelial layer was disrupted in numerous locations. Complete disruption of all layers of the blood-gas barrier was occasionally present.Rapid reperfusion of the ischemic lung is an important contributing factor to reperfusion lung injury resulting in mechanical stress failure of the alveolar/capillary barrier. Gradual reintroduction of blood flow to the ischemic lung improves oxygenation.