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常温下离体灌注期间吲哚菁绿荧光定量评估循环死亡后猪供肝

Indocyanine green fluorescence quantification during normothermic ex situ perfusion for the assessment of porcine liver grafts after circulatory death.

机构信息

Department of Surgery, Ajmera Transplant Centre, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada.

Department of Surgery, Divisions of Hepato-biliary-Pancreatic Surgery and Transplantation, Kyoto University Graduate School of Medicine, Kyoto, Japan.

出版信息

Liver Transpl. 2024 Sep 1;30(9):907-917. doi: 10.1097/LVT.0000000000000416. Epub 2024 Jun 12.

DOI:10.1097/LVT.0000000000000416
PMID:38869990
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11332378/
Abstract

Current graft evaluation during normothermic ex situ liver perfusion lacks real-time parameters for predicting posttransplant hepatocyte and biliary function. Indocyanine green (ICG) imaging has been widely used in liver surgery, enabling the visualization of hepatic uptake and excretion through bile using near-infrared light. In this research, porcine livers under various ischemic conditions were examined during a 5-hour normothermic ex situ liver perfusion procedure, introducing ICG at 1 hour through the hepatic artery. These conditions included livers from heart-beating donors, donation after circulatory death (DCD) with warm ischemic durations of 60 minutes (DCD60) and 120 minutes (DCD120), as well as interventions utilizing tissue plasminogen activator in DCD120 cases (each n = 5). Distinct hepatic fluorescence patterns correlated with different degrees of ischemic injury ( p = 0.01). Low ICG uptake in the parenchyma (less than 40% of maximum intensity) was more prevalent in DCD120 (21.4%) compared to heart-beating donors (6.2%, p = 0.06) and DCD60 (3.0%, p = 0.02). Moreover, ICG clearance from 60 minutes to 240 minutes was significantly higher in heart-beating donors (69.3%) than in DCD60 (17.5%, p < 0.001) and DCD120 (32.1%, p = 0.01). Furthermore, thrombolytic intervention using tissue plasminogen activator in DCD120 resulted in noteworthy outcomes, including significantly reduced ALP levels ( p = 0.04) and improved ICG clearance ( p = 0.02) with a trend toward mitigating fibrin deposition similar to DCD60, as well as enhancements in bile production ( p = 0.09). In conclusion, ICG fluorescence imaging during normothermic ex situ liver perfusion provides real-time classification of hepatic vascular and biliary injuries, offering valuable insights for the more accurate selection and postintervention evaluation of marginal livers in transplantation.

摘要

在常温离体肝脏灌注过程中,当前的移植物评估缺乏预测移植后肝细胞和胆道功能的实时参数。吲哚菁绿(ICG)成像已广泛应用于肝外科,通过近红外光实现了对肝脏摄取和胆汁排泄的可视化。在这项研究中,在 5 小时常温离体肝脏灌注过程中检查了各种缺血条件下的猪肝脏,在 1 小时时通过肝动脉引入 ICG。这些条件包括心跳供体的肝脏、热缺血时间为 60 分钟(DCD60)和 120 分钟(DCD120)的捐赠后循环死亡(DCD)以及在 DCD120 病例中使用组织纤溶酶原激活物的干预(每组 n = 5)。不同的肝荧光模式与不同程度的缺血损伤相关(p = 0.01)。在 DCD120 中(低于最大强度的 40%),实质内 ICG 摄取较低(21.4%)比心跳供体(6.2%,p = 0.06)和 DCD60(3.0%,p = 0.02)更常见。此外,在心跳供体中,从 60 分钟到 240 分钟的 ICG 清除率明显更高(69.3%)比 DCD60(17.5%,p < 0.001)和 DCD120(32.1%,p = 0.01)。此外,在 DCD120 中使用组织纤溶酶原激活物进行溶栓干预产生了显著的结果,包括显著降低的 ALP 水平(p = 0.04)和改善的 ICG 清除率(p = 0.02),与 DCD60 相似,纤维蛋白沉积趋势减轻,胆汁产量增加(p = 0.09)。总之,常温离体肝脏灌注过程中的 ICG 荧光成像提供了实时的肝血管和胆道损伤分类,为更准确地选择和移植后评估边缘供肝提供了有价值的信息。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/76d0/11332378/8e33f00a217e/lvt-30-907-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/76d0/11332378/d9d9e182bd4a/lvt-30-907-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/76d0/11332378/eb969a670f1b/lvt-30-907-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/76d0/11332378/7ea2f516e898/lvt-30-907-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/76d0/11332378/e16ea930cec8/lvt-30-907-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/76d0/11332378/dfd9c33dc115/lvt-30-907-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/76d0/11332378/8e33f00a217e/lvt-30-907-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/76d0/11332378/d9d9e182bd4a/lvt-30-907-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/76d0/11332378/eb969a670f1b/lvt-30-907-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/76d0/11332378/7ea2f516e898/lvt-30-907-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/76d0/11332378/e16ea930cec8/lvt-30-907-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/76d0/11332378/dfd9c33dc115/lvt-30-907-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/76d0/11332378/8e33f00a217e/lvt-30-907-g006.jpg

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Hypothermic machine perfusion before viability testing of previously discarded human livers.在对先前废弃的人体肝脏进行生存能力测试之前进行低温机器灌注。
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Microvascular obstructions in portal bile duct capillaries and hepatic sinusoids during normothermic machine perfusion of marginal human livers.
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Am J Transplant. 2021 Apr;21(4):1662-1664. doi: 10.1111/ajt.16337. Epub 2020 Oct 30.
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Lysis of cold-storage-induced microvascular obstructions for ex vivo revitalization of marginal human kidneys.冷储存诱导的微血管阻塞的溶解用于体外人类边缘肾脏的再生活性化。
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