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BACKGROUND: Optimal preservation of post-ischemic organ function is a continuing challenge in clinical lung transplantation. Retrograde instillation of preservation solutions has the theoretic advantage of achieving homogeneous distribution in the lung because of perfusing both the pulmonary and the bronchial circulation. So far, we have seen no experimental studies that include stereologic analysis of intrapulmonary edema concerning the influence of retrograde preservation on post-ischemic lung function after preservation with Perfadex and Celsior. METHODS: In an extracorporeal rat model, we perfused 8 lungs, each, using either antegrade or retrograde perfusion technique with Celsior (CE(ant)/CE(ret)) and Perfadex (PER(ant)/PER(ret)). Results were compared with low-potassium Euro-Collins. Post-ischemic lungs were reventilated and reperfused mechanically. We continuously monitored relative oxygenation capacity (ROC), pulmonary artery pressure, flush time, and wet/dry ratio. Furthermore, we used stereologic means to evaluate edema formation. Statistics comprised different analysis of variance models. RESULTS: Relative oxygen capacity of CE(ant)-protected lungs was superior to that of PER(ant) preservation (p = 0.05). Use of PER(ret) resulted in significantly higher ROC as compared with PER(ant) (p < 0.001) and was comparable to results obtained with CE-preservation, which was not further improved with retrograde application. CONCLUSIONS: Celsior provides better lung preservation than does Perfadex when administered antegradely. Retrograde application of Perfadex results in significant functional improvement as compared with antegrade perfusion, which reaches the standard of Celsior-protected organs. Additional in vivo experiments in combination with ultrastructural analysis are warranted to further evaluate retrograde delivery of preservation solutions, which could be used in clinical lung transplantation to further optimize current results.