49 - Freie Mitteilung
Clinical works II
16. Mai 2019, 10:15 - 11:45, Bellavista 2, 6. OG
Pattern of release of damage associated molecular patterns after experimental ex-vivo lung perfusion and lung transplantation
A. Hasenauer1, E. Abdelnour-Berchtold1, B. Bédat2, R. Parapanov1, A. Debonneville1, M. Gonzalez1, J.-Y. Perentes1, H.-B. Ris1, J. Lugrin1, L. Liaudet1, T. Krueger1, Presenter: A. Hasenauer1 (1Lausanne, 2Geneva)
The release of damage associated molecular patterns (DAMPs) by injured cells during reperfusion may trigger innate immune responses after lung transplantation (LTx). The pattern of DAMPs release following LTx, and the possible influence of ex vivo lung perfusion (EVLP), is largely undefined. We evaluated the release of 4 major DAMPs by lung grafts during EVLP and after Ltx in a rat model. We also sought to compare the release of DAMPs by lungs grafts obtained after either cold or warm ischemia.
4 groups of donor lungs were investigated: (1) Cold ischemia (CI): lungs stored at 4°C for 7 h; (2) Warm ischemia (WI): Lungs kept at room temperature (RT) for 1h, then 6h at 4°C; (3) Cold ischemia plus EVLP (CIE). Lungs stored at 4°C for 2 h, followed by EVLP for 3 h and additional storage at 4°c for 2h. (4) Warm ischemia plus EVLP (WIE): Lungs kept at RT for 1h, followed by 1h at 4°C and then EVLP as above. At the end of storage and EVLP, the right lung was used for bronchoalveolar lavage (BAL) and the left lung for Ltx, with its BAL collected after 2 h reperfusion. The Steen® solution used for EVLP was also collected. The DAMPs HMGB1, S100A8, IL-33 and HSP-70 were determined by ELISAs in the BAL and Steen®.
At the end of preservation and EVLP, high levels of HMGB1, IL-33, S100A8 and Hsp70 were recovered in the BAL of all 4 groups with no significant differences, except from Hsp70, significantly reduced in WIE group. In Steen® solution, very high DAMPs levels were recovered in similar concentrations in CIE and WIE. After LTx, lungs exposed to WI tended to display increased levels of HMGB1 and IL-33, and had significantly lower levels of Hsp70, irrespective of EVLP.
Major DAMPs are released by lung allografts both after CI or WI, with minor influence of EVLP. Hsp70 is reduced after WI, irrespective from EVLP. These findings open new perspective for the understanding of innate immune activation following EVLP and LTx.