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低流量去细胞和高流量细胞外肺灌注系统中长时间冷缺血后排斥供体肺的移植适应性。

Transplant Suitability of Rejected Human Donor Lungs With Prolonged Cold Ischemia Time in Low-Flow Acellular and High-Flow Cellular Ex Vivo Lung Perfusion Systems.

机构信息

Department of Pathobiology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH.

Department of Thoracic and Cardiovascular Surgery, Cleveland Clinic, Cleveland, OH.

出版信息

Transplantation. 2019 Sep;103(9):1799-1808. doi: 10.1097/TP.0000000000002667.

Abstract

BACKGROUND

Ex vivo lung perfusion (EVLP) has the potential to increase the number of donor lungs available for lung transplantation (LTx). While the current maximum cold ischemia time (CIT) for donor lungs in clinical LTx is around 8 hours, there are no data regarding the potential use of rejected donor lungs with CIT >8 hours before EVLP. The purpose of this study was to investigate the transplant suitability of lungs with a prolonged CIT in 2 EVLP systems.

METHODS

Following prolonged CIT of 13.8 hours (range 9.0-19.5 h), 16 rejected human donor lungs were randomly divided and perfused using either low-flow acellular or high-flow cellular EVLP systems (n = 8, each). Transplant suitability was evaluated according to the standard criteria of each EVLP system.

RESULTS

The high-flow cellular group was associated with a significantly lower transplant suitability (0% versus 37%, P = 0.027), significantly lower wet-to-dry ratio change (-0.71 ± 0.62 versus 0.43 ± 1.01, P = 0.035), and lower pathological score (1.62 ± 0.61 versus 3.00 ± 0.61, P = 0.163) than the low-flow acellular group. In both systems, inflammatory cytokines on perfusate (tumor necrosis factor-α, interleukin [IL]-1ß, IL-6, IL-8, and IL-10) increased in a time-dependent manner and were significantly higher than those of controls with CIT <8 hours (P < 0.05).

CONCLUSIONS

The potential for reconditioning lungs with a CIT >8 hours is diminished compared with that for lungs having a shorter CIT due to severe ischemia reperfusion injury.

摘要

背景

离体肺灌注 (EVLP) 有可能增加可用于肺移植 (LTx) 的供肺数量。 虽然目前临床 LTx 中供肺的最大冷缺血时间 (CIT) 约为 8 小时,但对于 CIT >8 小时之前接受 EVLP 的废弃供肺的潜在用途尚无数据。 本研究的目的是在 2 种 EVLP 系统中研究 CIT 延长的肺的移植适用性。

方法

在延长 CIT 13.8 小时(范围 9.0-19.5 h)后,16 个废弃的人类供肺被随机分为两组,分别使用低流量无细胞或高流量细胞 EVLP 系统进行灌注(每组 8 个)。 根据每个 EVLP 系统的标准标准评估移植适用性。

结果

高流量细胞组的移植适用性显著降低(0%比 37%,P = 0.027),湿干比变化显著降低(-0.71 ± 0.62 比 0.43 ± 1.01,P = 0.035),病理评分较低(1.62 ± 0.61 比 3.00 ± 0.61,P = 0.163)比低流量无细胞组。 在这两种系统中,灌洗液中的炎性细胞因子(肿瘤坏死因子-α、白细胞介素 [IL]-1β、IL-6、IL-8 和 IL-10)呈时间依赖性增加,并且明显高于 CIT <8 小时的对照组(P <0.05)。

结论

与 CIT 较短的肺相比,CIT >8 小时的肺的再调理潜力降低,因为严重的缺血再灌注损伤。

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