| 1. |
- Reichart, Bruno, et al.
(författare)
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Pig-to-non-human primate heart transplantation : The final step toward clinical xenotransplantation?
- 2020
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Ingår i: Journal of Heart and Lung Transplantation. - : Elsevier BV. - 1053-2498. ; 39:8, s. 751-757
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Tidskriftsartikel (refereegranskat)abstract
- Background: The demand for donated human hearts far exceeds the number available. Xenotransplantation of genetically modified porcine organs provides an alternative. In 2000, an Advisory Board of the International Society for Heart and Lung Transplantation set the benchmark for commencing clinical cardiac xenotransplantation as consistent 60% survival of non-human primates after life-supporting porcine heart transplantations. Recently, we reported the stepwise optimization of pig-to-baboon orthotopic cardiac xenotransplantation finally resulting in consistent success, with 4 recipients surviving 90 (n = 2), 182, and 195 days. Here, we report on 4 additional recipients, supporting the efficacy of our procedure. Results: The first 2 additional recipients succumbed to porcine cytomegalovirus (PCMV) infections on Days 15 and 27, respectively. In 2 further experiments, PCMV infections were successfully avoided, and 3-months survival was achieved. Throughout all the long-term experiments, heart, liver, and renal functions remained within normal ranges. Post-mortem cardiac diameters were slightly increased when compared with that at the time of transplantation but with no detrimental effect. There were no signs of thrombotic microangiopathy. The current regimen enabled the prolonged survival and function of orthotopic cardiac xenografts in altogether 6 of 8 baboons, of which 4 were now added. These results exceed the threshold set by the Advisory Board of the International Society for Heart and Lung Transplantation. Conclusions: The results of our current and previous experimental cardiac xenotransplantations together fulfill for the first time the pre-clinical efficacy suggestions. PCMV-positive donor animals must be avoided.
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| 2. |
- Stone, John P, et al.
(författare)
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Mechanical removal of dendritic cell-generating non-classical monocytes via ex vivo lung perfusion.
- 2014
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Ingår i: The Journal of Heart and Lung Transplantation. - : Elsevier BV. - 1557-3117 .- 1053-2498. ; 33:8, s. 864-869
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Tidskriftsartikel (refereegranskat)abstract
- Ex vivo lung perfusion (EVLP) is a novel procedure designed to rapidly assess and recondition unusable donor lungs for transplantation (LTx). EVLP may reduce graft immunogenicity and allorecognition via removal of passenger leukocytes. We aimed to explore this hypothesis using human EVLP and in vitro analysis.
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| 3. |
- Wallinder, Andreas, 1977, et al.
(författare)
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A simplified preservation method for lungs donated after cardiac death
- 2014
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Ingår i: Journal of Heart and Lung Transplantation. - : Elsevier BV. - 1053-2498 .- 1557-3117. ; 33:5, s. 528-535
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Tidskriftsartikel (refereegranskat)abstract
- Background The shortage of donor lungs restricts the number of lung transplantations that can be performed. However, extension of the donor pool using organs donated after cardiac death (DCD) could potentially increase the number of patients who undergo transplantation. To establish acceptance among hospital personnel and the donor's next of kin for the uncontrolled DCD procedure we proposed a simplified preservation regime for intrapleural cooling of the donor lungs. METHODS: In an uncontrolled DCD model, 12 pigs were randomized to intrapleural lung cooling using either a standard method with two bilateral chest tubes and intermittent pleural fluid exchanges, or a simplified, less-invasive method with a single bilateral chest tube and filling of the pleural space without fluid exchange. Lungs were explanted and graft function was assessed during ex vivo lung perfusion (EVLP) and by histologic examination. RESULTS: Although the mean temperature after 120 minutes of intrapleural cooling was significantly higher in the lungs cooled using the simplified method (25.9 degrees C vs 13.5 degrees C), this did not affect the oxygenation capacity, pulmonary vascular resistance or dynamic compliance of the lungs, as recorded during EVLP. Furthermore, no differences were found between the lungs preserved by the two methods with respect to the wet/dry ratio, levels of myeloperoxidase in bronchoalveolar lavage, or at histologic examination. CONCLUSIONS: The simplified technique for DCD lung cooling results in a higher preservation temperature but does not affect lung function during EVLP, which implies that this less invasive method can be used in the uncontrolled DCD setting. This is another step forward in the development of a simplified preservation routine for DCD. (C) 2014 International Society for Heart and Lung Transplantation. All rights reserved.
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| 4. |
- Wierup, P, et al.
(författare)
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Lung edema formation during cold perfusion: Important differences between rat and porcine lung
- 2005
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Ingår i: The Journal of Heart and Lung Transplantation. - : Elsevier BV. - 1557-3117 .- 1053-2498. ; 24:4, s. 379-385
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Tidskriftsartikel (refereegranskat)abstract
- Background: The aim of this study was to investigate the effect of different perfusion pressures on edema formation during cold flush perfusion with the 2 most commonly used preservation solutions in clinical lung transplantation: Euro-Collins and Perfadex solutions. Methods: Isolated rat and porcine lungs were perfused for 3 minutes at 4 degrees C to 8 degrees C at a pressure of either 10, 15 or 20 mm, Hg. Weight gain was recorded continuously. Weight gain per minute was calculated after the first phase of rapid weight gain was completed. Results: In the rat model, perfusion pressure of 10 mm Hg resulted in a macro- and microscopically apparent edema, irrespective of the type of preservation solution. Perfusion pressures of 10, 15 and 20 nun Hg gave weight gains of 100%, 150% and 350%, respectively, after 3 minutes of perfusion. The corresponding weight gain per minute was 18%, 31% and 84% of the initial weight. There were no statistically significant differences in weight gain between the different solutions at equal perfusion pressure. In the porcine model the flow was extremely low at 10 mm Hg and no weight gain was registered, whereas the weight gain per minute at 15 and 20 mm Hg was 1.0% and 2.1% of the initial weight. Conclusions: In porcine lungs, cold perfusion at 20 mm Hg gives minimal edema formation, whereas in rat lungs the edema formation is deleterious, irrespective of the solution used.
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