Neutrophil extracellular traps removal using ex vivo lung perfusion restored lung function in gastric aspiration damaged porcine lungs
Margareta Mittendorfer1,2, Leif Pierre1,2, Andrew Aswani3, Gunilla Kjellberg 4, Franziska Olm1,2, Sandra Lindstedt1,2.
1Department of Cardiothoracic Surgery and Transplantation, Lund University Hospital, Lund, Sweden; 2Department of Clinical Sciences, Lund University, Lund, Sweden; 3Department of Critical Care, Guy’s and St Thomas’s NHS Foundation Trust, London, United Kingdom; 4Department of Thoracic Surgery and Anesthesiology, Uppsala University Hospital, Uppsala, Sweden
Background: Lung transplantation (LTx) is an established therapeutic option for end-stage pulmonary disease. However, it remains hampered by donor lung scarcity. Treatments which could regenerate lungs rejected for transplant should be explored in order to combat waiting list mortality. Aspiration induced acute lung injury (ALI) is one of the contributes to the low utilization of donor lungs. Neutrophil extracellular traps (NETs) are implicated in the inflammation profile of ALI. Reduction of NETs could be used as a therapeutic option with the arrival of devices specific to their removal. NucleoCapture device selectively removes NETs from the blood by utilizing human histone H1.3 protein conjugated to polymer beads. This study investigated the impact of the NETs capture device during ex vivo lung perfusion (EVLP) on ALI damaged lungs.
Methods: Healthy pigs (n=12) were stratified into two groups, treated (n=6) and not treated (n=6). All animals received 4ml/kg body weight gastric content distributed equally between the different lung segments using a bronchoscopy to induce acute lung injury. Mild to moderate ARDS was developed over 6 hours and confirmed via blood gas values, chest x-ray imaging and histological examination. Lungs were subsequently explanted en bloc and placed on EVLP for 4 hours. Treated lungs were placed in line with a NucleoCapture device connected to the EVLP circuit and the non-treated group underwent the same EVLP protocol without the device.
Results: Aspiration induced ALI was induced in all subjects as confirmed by infiltration on chest x-ray, histopathological examination and by PaO2/FiO2 ratio. Following treatment with the NucleoCapture device during 4 hours of EVLP, the PaO2/FiO2 ratio was significantly increased compared to non-treated lungs and was found to surpass the threshold values suitable for transplantation. Furthermore, macroscopic evaluation of the treated lungs demonstrated improvement relative to both the initial injury as well as comparison with the non-treated cohort.
Conclusions: Removal of NETs using the NucleoCapture device did restored lung function in aspiration damaged lungs. The amelioration of lung function by removing NETs shows potential clinical use of the device to increase the donor lung pool for lung transplantation.
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