title: Steroids can reduce warm ischemic reperfusion injury in a porcine donation after circulatory death model with ex vivo lung perfusion evaluation.
abstract: Donation after circulatory death (DCD) is being used to increase the number of transplantable organs. The role and timing of steroids in DCD donation and ex vivo lung perfusion (EVLP) has not been thoroughly investigated. In this study, we investigated the effect of steroids on warm ischemic injury in a porcine model (n = 6/group). Following cardiac arrest, grafts were left untouched in the donor (90-min warm ischemia). Graft function was assessed after 6 h of EVLP. In the MP group, 500 mg methylprednisolone was given prior to cardiac arrest and during EVLP. In the CONTR group, no steroids were added. Median lung compliance (13 ml/cmH20) was significantly better preserved in the CONTR group than in the MP group (30.5 ml/cmH20). Also, median wet-to-dry weight (6.11 vs. 6.94) and CT density (182.5 vs. 352.9 g/l) were significantly better in the MP group than in the CONTR group, respectively. There was no difference in oxygenation and pulmonary vascular resistance. Perfusate cytokine analysis showed a significant reduction in IL-1β, IL-8, IFN-α, IL-10, TNF-α, and IFN-γ in MP. Cytokines in bronchoalveolar lavage were not decreased except for IFN-gamma. We demonstrated that warm ischemic injury in DCD donation can be attenuated by steroids when given prior to warm ischemia and during EVLP. Ethical context of donor preconditioning should be discussed further.
authors: Laboratory of Anesthesiology and Algology, Department of Cardiovascular Sciences, Katholieke Universiteit Leuven and University Hospitals, Leuven, Belgium.|Leuven Lung Transplant Unit, Katholieke Universiteit Leuven, Leuven, Belgium.
authors: An
authors: A
authors: Martens
authors: Laboratory of Experimental Thoracic Surgery, Department of Clinical and Experimental Medicine, Katholieke Universiteit Leuven and University Hospitals, Leuven, Belgium.
authors: Marc
authors: M
authors: Boada
authors: Leuven Lung Transplant Unit, Katholieke Universiteit Leuven, Leuven, Belgium.|Lung Transplant Unit, Laboratory of Pneumology, Department of Clinical and Experimental Medicine, Katholieke Universiteit Leuven and University Hospitals, Leuven, Belgium.
authors: Bart M
authors: BM
authors: Vanaudenaerde
authors: Leuven Lung Transplant Unit, Katholieke Universiteit Leuven, Leuven, Belgium.|Lung Transplant Unit, Laboratory of Pneumology, Department of Clinical and Experimental Medicine, Katholieke Universiteit Leuven and University Hospitals, Leuven, Belgium.
authors: Stijn E
authors: SE
authors: Verleden
authors: Leuven Lung Transplant Unit, Katholieke Universiteit Leuven, Leuven, Belgium.|Lung Transplant Unit, Laboratory of Pneumology, Department of Clinical and Experimental Medicine, Katholieke Universiteit Leuven and University Hospitals, Leuven, Belgium.
authors: Robin
authors: R
authors: Vos
authors: Leuven Lung Transplant Unit, Katholieke Universiteit Leuven, Leuven, Belgium.|Lung Transplant Unit, Laboratory of Pneumology, Department of Clinical and Experimental Medicine, Katholieke Universiteit Leuven and University Hospitals, Leuven, Belgium.
authors: Geert M
authors: GM
authors: Verleden
authors: Department of Histopathology, University Hospitals Leuven, Leuven, Belgium.
authors: Eric K
authors: EK
authors: Verbeken
authors: Leuven Lung Transplant Unit, Katholieke Universiteit Leuven, Leuven, Belgium.|Laboratory of Experimental Thoracic Surgery, Department of Clinical and Experimental Medicine, Katholieke Universiteit Leuven and University Hospitals, Leuven, Belgium.
authors: Dirk
authors: D
authors: Van Raemdonck
authors: Laboratory of Virology and Chemotherapy (Rega Institute), Department of Microbiology and Immunology, Katholieke University Leuven, Leuven, Belgium.
authors: Dominique
authors: D
authors: Schols
authors: Laboratory of Virology and Chemotherapy (Rega Institute), Department of Microbiology and Immunology, Katholieke University Leuven, Leuven, Belgium.
authors: Sandra
authors: S
authors: Claes
authors: Laboratory of Anesthesiology and Algology, Department of Cardiovascular Sciences, Katholieke Universiteit Leuven and University Hospitals, Leuven, Belgium. arne.neyrinck@uzleuven.be.|Leuven Lung Transplant Unit, Katholieke Universiteit Leuven, Leuven, Belgium. arne.neyrinck@uzleuven.be.
authors: Arne P
authors: AP
authors: Neyrinck
mesh_terms: D000818:Animals; D018893:Bronchoalveolar Lavage; D016207:Cytokines / Q000378:metabolism; D005112:Extracorporeal Circulation; D006323:Heart Arrest / Q000517:prevention & control; D008168:Lung / Q000473:pathology / Q000502:physiology; D016040:Lung Transplantation; D008775:Methylprednisolone / Q000627:therapeutic use; D010100:Oxygen / Q000378:metabolism; D010477:Perfusion; D015427:Reperfusion Injury / Q000188:drug therapy / Q000473:pathology*; D013256:Steroids / Q000627:therapeutic use*; D013552:Swine; D013997:Time Factors; D052096:Warm Ischemia
chemical_list: D016207:Cytokines; D013256:Steroids; D010100:Oxygen; D008775:Methylprednisolone
keywords: animal models; donation; donation after circulatory death; donor management; ex vivo lung perfusion; experimental transplantation; extended donor pool; ischemia reperfusion injury; organ preservation and procurement