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• W4225464089 abstract "PurposeMononuclear phagocytes (MPs) play a key role in post-lung transplantation (LTx) ischemia-reperfusion injury (IRI). Clodronate-liposome is a promising drug for the depletion of MPs. We hypothesized that the administration of clodronate-liposome into the perfusate during ex vivo lung perfusion (EVLP) could reduce MPs and attenuate IRI in a rat LTx model.MethodsLewis rat lungs were flushed with Perfadex® solution and stored for 15 h at 4°C. In Experiment I, grafts were allocated to two groups: control and clodronate (n = 5 each). In the clodronate group, 3 mL of clodronate-liposome was administered into the perfusate before EVLP. After 4 h of EVLP, the amounts of MPs in the perfusate and digested lung tissue were measured via flow cytometry. In Experiment II, grafts were similarly allocated to two groups: control and clodronate (n = 6 each). After 4 h of EVLP, left lungs were transplanted and reperfused for 2 h. Lung function was then evaluated, and samples were collected. The Mann-Whitney U test was used for comparing the two groups. Repeated measures analysis of variance was used for comparing data obtained during EVLP.ResultsIn Experiment I, the amounts of MPs were significantly reduced in the clodronate group (P=0.008, Figure 1A). In Experiment II, compliance and vascular resistance during EVLP were significantly better in the clodronate group than in the control group (P<0.001 and P<0.001, respectively). Two hours after reperfusion, the PaO2/FiO2 ratio from the pulmonary vein was significantly higher in the clodronate group (P=0.015, Figure 1B), whereas the wet-to-dry weight ratio was significantly lower (P=0.026). Regarding scoring of histological findings, less lung injury was observed in the clodronate group than in the control group (P=0.013).ConclusionThe administration of clodronate-liposome into the perfusate during EVLP demonstrated significant attenuation of MPs in the donor lungs and IRI post-LTx. Mononuclear phagocytes (MPs) play a key role in post-lung transplantation (LTx) ischemia-reperfusion injury (IRI). Clodronate-liposome is a promising drug for the depletion of MPs. We hypothesized that the administration of clodronate-liposome into the perfusate during ex vivo lung perfusion (EVLP) could reduce MPs and attenuate IRI in a rat LTx model. Lewis rat lungs were flushed with Perfadex® solution and stored for 15 h at 4°C. In Experiment I, grafts were allocated to two groups: control and clodronate (n = 5 each). In the clodronate group, 3 mL of clodronate-liposome was administered into the perfusate before EVLP. After 4 h of EVLP, the amounts of MPs in the perfusate and digested lung tissue were measured via flow cytometry. In Experiment II, grafts were similarly allocated to two groups: control and clodronate (n = 6 each). After 4 h of EVLP, left lungs were transplanted and reperfused for 2 h. Lung function was then evaluated, and samples were collected. The Mann-Whitney U test was used for comparing the two groups. Repeated measures analysis of variance was used for comparing data obtained during EVLP. In Experiment I, the amounts of MPs were significantly reduced in the clodronate group (P=0.008, Figure 1A). In Experiment II, compliance and vascular resistance during EVLP were significantly better in the clodronate group than in the control group (P<0.001 and P<0.001, respectively). Two hours after reperfusion, the PaO2/FiO2 ratio from the pulmonary vein was significantly higher in the clodronate group (P=0.015, Figure 1B), whereas the wet-to-dry weight ratio was significantly lower (P=0.026). Regarding scoring of histological findings, less lung injury was observed in the clodronate group than in the control group (P=0.013). The administration of clodronate-liposome into the perfusate during EVLP demonstrated significant attenuation of MPs in the donor lungs and IRI post-LTx." @default.
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• W4225464089 date "2022-04-01" @default.
• W4225464089 modified "2023-09-28" @default.
• W4225464089 title "Reduction of Donor Mononuclear Phagocytes During Ex Vivo Lung Perfusion Attenuates Ischemia-Reperfusion Injury in a Rat Lung Transplantation Model" @default.
• W4225464089 doi "https://doi.org/10.1016/j.healun.2022.01.760" @default.
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