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Title: An evaluation of cellular and molecular mechanisms of donor lung reconditioning during human ex-vivo lung perfusion
Author: Andreasson, Anders S. I.
ISNI:       0000 0004 7425 250X
Awarding Body: University of Newcastle upon Tyne
Current Institution: University of Newcastle upon Tyne
Date of Award: 2017
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Background Donor lungs not deemed suitable for immediate transplantation may be reconditioned using ex-vivo lung perfusion (EVLP). The objective identification of which donor lungs can be successfully reconditioned and will function well post-transplant has not yet been established. Aim To characterise physiological, microbiological, and immunological changes during clinical EVLP and evaluate their association with transplant outcome and cellular changes during perfusion. Methods In two cohorts of rejected donor lungs undergoing clinical EVLP, microbial load in bronchoalveolar lavage fluid (BAL) and markers of inflammation and tissue injury in perfusate, BAL, and lung tissue were examined. An in vitro model of neutrophil adherence to lung vasculature was used to evaluate endothelial activation in response to perfusate fluid. Results In consecutive cohorts, bacterial loads in BAL were significantly reduced after EVLP with high-dose antibiotics in the perfusate. Yeast loads increased when no anti-fungal treatment was given, but were reduced when prophylactic anti-fungal treatment was added. The most effective markers to differentiate in-hospital Survival from Non-survival post-transplant were perfusate IL-lp (AUC=1.00, p=0.002) and TNF-a (AUC=0.95, p=0.006) after 30 minutes of EVLP.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available