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OBJECTIVES Volatile anaesthetics can provide significant protection against reperfusion injury in various experimental settings. The aim of this study was to assess the potential of sevoflurane treatment, the most commonly used volatile anaesthetic in modern anaesthesia, in rat lungs donated after circulatory death and reconditioned in an ex vivo lung perfusion (EVLP) system. METHODS Fifteen rats were sacrificed and divided into 3 groups. In the control and sevoflurane groups, the heart-lung blocks were exposed to 1 h of warm ischaemia and 2 h of cold ischaemia and were mounted on an EVLP circuit for 3 h, in the absence or in the presence of 2% sevoflurane. In the baseline group, heart-lung blocks were harvested immediately after euthanasia. Physiological data, lung nitro-oxidative stress, lactate dehydrogenase (LDH), expression of cytokines, oedema and histopathological findings were assessed during or post-EVLP. RESULTS The sevoflurane group showed significantly reduced LDH (8.82 ± 3.58 arbitrary unit vs 3.80 ± 3.02 arbitrary unit, P = 0.03), protein carbonyl (1.17 ± 0.44 nmol⋅mg−1 vs 0.55 ± 0.11 nmol⋅mg−1, P = 0.006), 3-nitrotyrosine (197.44 ± 18.47 pg⋅mg−1 vs 151.05 ± 23.54 pg⋅mg−1, P = 0.004), cytokine-induced neutrophil chemoattractant factor 1 (1.17 ± 0.32 ng⋅mg−1 vs 0.66 ± 0.28 ng⋅mg−1, P = 0.03) and tumour necrosis factor alpha (1.50 ± 0.59 vs 0.59 ± 0.38 ng⋅mg−1, P = 0.02) when compared with the control group. In addition, sevoflurane lungs gained significantly less weight (0.72 ± 0.09 g vs 0.72 ± 0.09 g, P = 0.044), had less perivascular oedema (0.58 ± 0.09 vs 0.47 ± 0.07, P = 0.036), and improved static pulmonary compliance (+0.215 ml⋅cmH2O−1, P = 0.003) and peak airways pressure (-1.33 cmH2O, P = 0.04) but similar oxygenation capacity (+1.61 mmHg, P = 0.77) and pulmonary vascular resistances (+0.078 mmHg⋅min⋅ml−1, P = 0.15) when compared with the control group. CONCLUSIONS These findings suggest that the potential of sevoflurane in protecting t

OBJECTIVES Malignant pleural mesothelioma (MPM) is a deadly disease with limited treatment options. Approaches to enhance patient immunity against MPM have been tested but shown variable results. Previously, we have demonstrated interesting vascular modulating properties of low-dose photodynamic therapy (L-PDT) on MPM. Here, we hypothesized that L-PDT vascular modulation could favour immune cell extravasation in MPM and improve tumour control in combination with immune checkpoint inhibitors. METHODS First, we assessed the impact of L-PDT on vascular endothelial E-selectin expression, a key molecule for immune cell extravasation, in vitro and in a syngeneic murine model of MPM. Second, we characterized the tumour immune cell infiltrate by 15-colour flow cytometry analysis 2 and 7 days after L-PDT treatment of the murine MPM model. Third, we determined how L-PDT combined with immune checkpoint inhibitor anti-CTLA4 affected tumour growth in a murine MPM model. RESULTS L-PDT significantly enhanced E-selectin expression by endothelial cells in vitro and in vivo. This correlated with increased CD8+ T cells and activated antigen-presenting cells (CD11b+ dendritic cells and macrophages) infiltration in MPM. Also, compared to anti-CTLA4 that only affects tumour growth, the combination of L-PDT with anti-CTLA4 caused complete MPM regression in 37.5% of animals. CONCLUSIONS L-PDT enhances E-selectin expression in the MPM endothelium, which favours immune infiltration of tumours. The combination of L-PDT with immune checkpoint inhibitor anti-CTLA4 allows best tumour control and regression., info:eu-repo/semantics/published