Functional, Metabolic and Morphologic Results of Ex Vivo Donor Lung Perfusion with a Perfluorocarbon-Based Oxygen Carrier Nanoemulsion in a Large Animal Transplantation Model
Background: Ex vivo lung perfusion (EVLP) is a technology that allows the re-evaluation of questionable donor lung before implantation and it has the potential to repair injured donor lungs that are otherwise unsuitable for transplantation. We hypothesized that perfluorocarbon-based oxygen carrier,...
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MDPI AG
2020-11-01
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| Online Access: | https://www.mdpi.com/2073-4409/9/11/2501 |
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| author | Ilhan Inci Stephan Arni Ilker Iskender Necati Citak Josep Monné Rodriguez Miriam Weisskopf Isabelle Opitz Walter Weder Thomas Frauenfelder Marie Pierre Krafft Donat R. Spahn |
| author_facet | Ilhan Inci Stephan Arni Ilker Iskender Necati Citak Josep Monné Rodriguez Miriam Weisskopf Isabelle Opitz Walter Weder Thomas Frauenfelder Marie Pierre Krafft Donat R. Spahn |
| author_sort | Ilhan Inci |
| collection | DOAJ |
| description | Background: Ex vivo lung perfusion (EVLP) is a technology that allows the re-evaluation of questionable donor lung before implantation and it has the potential to repair injured donor lungs that are otherwise unsuitable for transplantation. We hypothesized that perfluorocarbon-based oxygen carrier, a novel reconditioning strategy instilled during EVLP would improve graft function. Methods: We utilized perfluorocarbon-based oxygen carrier (PFCOC) during EVLP to recondition and improve lung graft function in a pig model of EVLP and lung transplantation. Lungs were retrieved and stored for 24 h at 4 °C. EVLP was done for 6 h with or without PFCOC. In the transplantation groups, left lung transplantation was done after EVLP with or without PFCOC. Allograft function was assessed by means of pulmonary gas exchange, lung mechanics and vascular pressures, histology and transmission electron microscopy (TEM). Results: In the EVLP only groups, physiological and biochemical markers during the 6-h perfusion period were comparable. However, perfusate lactate potassium levels were lower and ATP levels were higher in the PFCOC group. Radiologic assessment revealed significantly more lung infiltrates in the controls than in the PFCOC group (<i>p</i> = 0.04). In transplantation groups, perfusate glucose consumption was higher in the control group. Lactate levels were significantly lower in the PFCOC group (<i>p</i> = 0.02). Perfusate flavin mononucleotide (FMN) was significantly higher in the controls (<i>p</i> = 0.008). Post-transplant gas exchange was significantly better during the 4-h reperfusion period in the PFCOC group (<i>p</i> = 0.01). Plasma IL-8 and IL-12 levels were significantly lower in the PFCOC group (<i>p</i> = 0.01, <i>p</i> = 0.03, respectively). ATP lung tissue levels at the end of the transplantation were higher and myeloperoxidase (MPO) levels in lung tissue were lower in the PFCOC group compared to the control group. In the PFCOC group, TEM showed better tissue preservation and cellular viability. Conclusion: PFCOC application is safe during EVLP in lungs preserved 24 h at 4 °C. Although this strategy did not significantly affect the EVLP physiology, metabolic markers of the donor quality such as lactate production, glucose consumption, neutrophil infiltration and preservation of mitochondrial function were better in the PFCOC group. Following transplantation, PFCOC resulted in better graft function and TEM showed better tissue preservation, cellular viability and improved gas transport. |
| first_indexed | 2024-03-10T14:45:38Z |
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| language | English |
| last_indexed | 2024-03-10T14:45:38Z |
| publishDate | 2020-11-01 |
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| spelling | doaj.art-39d48e57bc194bf0915cade752998f412023-11-20T21:26:05ZengMDPI AGCells2073-44092020-11-01911250110.3390/cells9112501Functional, Metabolic and Morphologic Results of Ex Vivo Donor Lung Perfusion with a Perfluorocarbon-Based Oxygen Carrier Nanoemulsion in a Large Animal Transplantation ModelIlhan Inci0Stephan Arni1Ilker Iskender2Necati Citak3Josep Monné Rodriguez4Miriam Weisskopf5Isabelle Opitz6Walter Weder7Thomas Frauenfelder8Marie Pierre Krafft9Donat R. Spahn10Department of Thoracic Surgery, University Hospital Zurich–University of Zurich, CH-8091 Zurich, SwitzerlandDepartment of Thoracic Surgery, University Hospital Zurich–University of Zurich, CH-8091 Zurich, SwitzerlandDepartment of Thoracic Surgery, University Hospital Zurich–University of Zurich, CH-8091 Zurich, SwitzerlandDepartment of Thoracic Surgery, University Hospital Zurich–University of Zurich, CH-8091 Zurich, SwitzerlandInstitute of Veterinary Pathology, Vetsuisse Faculty, University of Zurich, CH-8057 Zurich, SwitzerlandDepartment of Surgical Research, University Hospital Zurich–University of Zurich, CH-8091 Zurich, SwitzerlandDepartment of Thoracic Surgery, University Hospital Zurich–University of Zurich, CH-8091 Zurich, SwitzerlandDepartment of Thoracic Surgery, University Hospital Zurich–University of Zurich, CH-8091 Zurich, SwitzerlandInstitute of Radiology, University Hospital Zurich–University of Zurich, CH-8091 Zurich, SwitzerlandInstitute Charles Sadron, CNRS, University of Strasbourg, 67200 Strasbourg, FranceInstitute of Anesthesiology, University Hospital Zurich-University of Zurich, CH-8091 Zurich, SwitzerlandBackground: Ex vivo lung perfusion (EVLP) is a technology that allows the re-evaluation of questionable donor lung before implantation and it has the potential to repair injured donor lungs that are otherwise unsuitable for transplantation. We hypothesized that perfluorocarbon-based oxygen carrier, a novel reconditioning strategy instilled during EVLP would improve graft function. Methods: We utilized perfluorocarbon-based oxygen carrier (PFCOC) during EVLP to recondition and improve lung graft function in a pig model of EVLP and lung transplantation. Lungs were retrieved and stored for 24 h at 4 °C. EVLP was done for 6 h with or without PFCOC. In the transplantation groups, left lung transplantation was done after EVLP with or without PFCOC. Allograft function was assessed by means of pulmonary gas exchange, lung mechanics and vascular pressures, histology and transmission electron microscopy (TEM). Results: In the EVLP only groups, physiological and biochemical markers during the 6-h perfusion period were comparable. However, perfusate lactate potassium levels were lower and ATP levels were higher in the PFCOC group. Radiologic assessment revealed significantly more lung infiltrates in the controls than in the PFCOC group (<i>p</i> = 0.04). In transplantation groups, perfusate glucose consumption was higher in the control group. Lactate levels were significantly lower in the PFCOC group (<i>p</i> = 0.02). Perfusate flavin mononucleotide (FMN) was significantly higher in the controls (<i>p</i> = 0.008). Post-transplant gas exchange was significantly better during the 4-h reperfusion period in the PFCOC group (<i>p</i> = 0.01). Plasma IL-8 and IL-12 levels were significantly lower in the PFCOC group (<i>p</i> = 0.01, <i>p</i> = 0.03, respectively). ATP lung tissue levels at the end of the transplantation were higher and myeloperoxidase (MPO) levels in lung tissue were lower in the PFCOC group compared to the control group. In the PFCOC group, TEM showed better tissue preservation and cellular viability. Conclusion: PFCOC application is safe during EVLP in lungs preserved 24 h at 4 °C. Although this strategy did not significantly affect the EVLP physiology, metabolic markers of the donor quality such as lactate production, glucose consumption, neutrophil infiltration and preservation of mitochondrial function were better in the PFCOC group. Following transplantation, PFCOC resulted in better graft function and TEM showed better tissue preservation, cellular viability and improved gas transport.https://www.mdpi.com/2073-4409/9/11/2501ex vivo lung perfusionoxygen carrierperfluorocarbonlung transplantation |
| spellingShingle | Ilhan Inci Stephan Arni Ilker Iskender Necati Citak Josep Monné Rodriguez Miriam Weisskopf Isabelle Opitz Walter Weder Thomas Frauenfelder Marie Pierre Krafft Donat R. Spahn Functional, Metabolic and Morphologic Results of Ex Vivo Donor Lung Perfusion with a Perfluorocarbon-Based Oxygen Carrier Nanoemulsion in a Large Animal Transplantation Model Cells ex vivo lung perfusion oxygen carrier perfluorocarbon lung transplantation |
| title | Functional, Metabolic and Morphologic Results of Ex Vivo Donor Lung Perfusion with a Perfluorocarbon-Based Oxygen Carrier Nanoemulsion in a Large Animal Transplantation Model |
| title_full | Functional, Metabolic and Morphologic Results of Ex Vivo Donor Lung Perfusion with a Perfluorocarbon-Based Oxygen Carrier Nanoemulsion in a Large Animal Transplantation Model |
| title_fullStr | Functional, Metabolic and Morphologic Results of Ex Vivo Donor Lung Perfusion with a Perfluorocarbon-Based Oxygen Carrier Nanoemulsion in a Large Animal Transplantation Model |
| title_full_unstemmed | Functional, Metabolic and Morphologic Results of Ex Vivo Donor Lung Perfusion with a Perfluorocarbon-Based Oxygen Carrier Nanoemulsion in a Large Animal Transplantation Model |
| title_short | Functional, Metabolic and Morphologic Results of Ex Vivo Donor Lung Perfusion with a Perfluorocarbon-Based Oxygen Carrier Nanoemulsion in a Large Animal Transplantation Model |
| title_sort | functional metabolic and morphologic results of ex vivo donor lung perfusion with a perfluorocarbon based oxygen carrier nanoemulsion in a large animal transplantation model |
| topic | ex vivo lung perfusion oxygen carrier perfluorocarbon lung transplantation |
| url | https://www.mdpi.com/2073-4409/9/11/2501 |
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