Background: Ischemia reperfusion injury (IRI) remains a major clinical problem in lung transplantation. Here, we report the investigation of IRI in a 17-year-old patient who underwent lung autotransplantation because of recurrent life threatening pulmonary bleedings due to repetitive ruptures of extraanatomic peribronchial systemic arteries. By explanting the left lung, it was possible to cut all extraanatomic vessels. To our knowledge, this is the first described case of an autotransplantation of a single lung for such an indication. This procedure was a unique chance to investigate isolated IRI as there is no alloreactivity.

Methods: Blood samples and broncheoalveolar lavage fluid (BALF) of the left and right lobe were collected before, intra and post autotransplantation. Plasma samples and BAL were analyzed for 100 cytokines and plasma factors with multiplex assays and for leukocyte subsets by FACS.

Results: 78 proteins showed a 3 to 100-fold increase during or post re-implantation in BALF of the left lung characterizing IRI. The fastest increase was seen for cytokines driven by innate signals like IL-6, IL-18 and chemokines recruiting monocytes and neutrophils like CXCL8, CCL2, CCL5. These factors increased also in BALF of the untreated right lung and systemically in plasma but delayed and lower. In contrast, T and NK cell derived cytokines (IFN-g, IL-2,4,10,17) and sCD25 were neither elevated in BALF nor in plasma. IRI also comprised tissue responses of epi- and endothelial cells, indicated by high levels of sICAM-1, sVCAM, sTie-2, VEGF, Ang-2 in the left lung BALF. High levels of urokinase (uPA) were detected in both BALFs while its inhibitor PAI-1 was also elevated in plasma.

Conclusions: These results from a unique human lung autotransplantation setting indicate that isolated IRI in the absence of alloreactivity can induce a strong cytokine/chemokine response, mainly by immune and non-immune cells, such as endothelial, epithelial and stroma cells. This strong inflammatory response was not limited to the re-implanted left lung, it was also detected delayed in the untreated right lung and systemically.

CITATION INFORMATION: Falk C, Tudorache I, Müller C, Sommer W, Daemen K, Keil J, Hansen G, Haverich A, Warnecke G, Schwerk N. Autotransplantation of the Left Lung for the Treatment of Recurrent Life Threatening Pulmonary Hemorrhage Related to Pulmonary Vascular Malformation: A Unique Chance to Study Ischemia/Reperfusion Injury. Am J Transplant. 2017;17 (suppl 3).

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