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基于全氟碳化合物的氧载体和亚常温肺机灌注减少促炎介质的产生。

Perfluorocarbon-Based Oxygen Carriers and Subnormothermic Lung Machine Perfusion Decrease Production of Pro-Inflammatory Mediators.

机构信息

Department of Thoracic Surgery, University Hospital Zürich, 8091 Zürich, Switzerland.

出版信息

Cells. 2021 Aug 30;10(9):2249. doi: 10.3390/cells10092249.

DOI:10.3390/cells10092249
PMID:34571898
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8466246/
Abstract

The quality of marginal donor lungs is clinically assessed with normothermic machine perfusion. Although subnormothermic temperature and perfluorocarbon-based oxygen carriers (PFCOC) have proven favourable for other organ transplants, their beneficial use for ex vivo lung perfusion (EVLP) still requires further investigation. In a rat model, we evaluated on a 4 h EVLP time the effects of PFCOC with either 28 °C or 37 °C perfusion temperatures. During EVLP at 28 °C with PFCOC, we recorded significantly lower lung pulmonary vascular resistance (PVR), higher dynamic compliance (Cdyn), significantly lower potassium and lactate levels, higher lung tissue ATP content, and significantly lower myeloperoxidase tissue activity when compared to the 37 °C EVLP with PFCOC. In the subnormothermic EVLP with or without PFCOC, the pro-inflammatory mediator TNFα, the cytokines IL-6 and IL-7, the chemokines MIP-3α, MIP-1α, MCP-1, GRO/KC as well as GM-CSF, G-CSF and the anti-inflammatory cytokines IL-4 and IL-10 were significantly lower. The 28 °C EVLP improved both Cdyn and PVR and decreased pro-inflammatory cytokines and pCO2 levels compared to the 37 °C EVLP. In addition, the 28 °C EVLP with PFCOC produced a significantly lower level of myeloperoxidase activity in lung tissue. Subnormothermic EVLP with PFCOC significantly improves lung donor physiology and ameliorates lung tissue biochemical and inflammatory parameters.

摘要

用常温机器灌注来临床评估边缘供体肺的质量。虽然亚常温温度和全氟化碳基氧载体(PFCOC)已被证明对其他器官移植有利,但它们在离体肺灌注(EVLP)中的有益应用仍需要进一步研究。在大鼠模型中,我们评估了在 4 小时 EVLP 时间内,28°C 或 37°C 灌注温度下 PFCOC 的效果。在 28°C 下用 PFCOC 进行 EVLP 时,与 37°C 下用 PFCOC 进行 EVLP 相比,我们记录到肺肺血管阻力(PVR)显著降低,动态顺应性(Cdyn)更高,钾和乳酸水平更低,肺组织 ATP 含量更高,髓过氧化物酶组织活性更低。在亚常温 EVLP 中,无论是否使用 PFCOC,促炎介质 TNFα、细胞因子 IL-6 和 IL-7、趋化因子 MIP-3α、MIP-1α、MCP-1、GRO/KC 以及 GM-CSF、G-CSF 和抗炎细胞因子 IL-4 和 IL-10 水平均显著降低。与 37°C EVLP 相比,28°C EVLP 改善了 Cdyn 和 PVR,并降低了促炎细胞因子和 pCO2 水平。此外,与 37°C EVLP 相比,28°C EVLP 加 PFCOC 使肺组织中的髓过氧化物酶活性显著降低。亚常温 EVLP 加 PFCOC 可显著改善供肺的生理学,并改善肺组织的生化和炎症参数。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c453/8466246/c72411a35be3/cells-10-02249-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c453/8466246/f9a901228cfc/cells-10-02249-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c453/8466246/c72411a35be3/cells-10-02249-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c453/8466246/f9a901228cfc/cells-10-02249-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c453/8466246/c72411a35be3/cells-10-02249-g002.jpg

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