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常温劈离式肝脏机器灌注:用于肝功能评估中稳健对照比较的方案,适用于临床前环境中新型治疗干预措施的评估。

Normothermic Split Liver Machine Perfusion: Protocol for Robust Comparative Controls in Liver Function Assessment Suitable for Evaluation of Novel Therapeutic Interventions in the Pre-clinical Setting.

作者信息

Attard Joseph A, Osei-Bordom Daniel-Clement, Boteon Yuri, Wallace Lorraine, Ronca Vincenzo, Reynolds Gary, Perera M T P R, Oo Ye Htun, Mergental Hynek, Mirza Darius F, Afford Simon C

机构信息

National Institute for Health Research (NIHR) Birmingham Biomedical Research Centre, University Hospitals Birmingham National Health Service (NHS) Foundation Trust, University of Birmingham, Birmingham, United Kingdom.

Centre for Liver and Gastrointestinal Research, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, United Kingdom.

出版信息

Front Surg. 2021 Feb 17;8:627332. doi: 10.3389/fsurg.2021.627332. eCollection 2021.

DOI:10.3389/fsurg.2021.627332
PMID:33681282
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7925992/
Abstract

donor liver machine perfusion is a promising tool to assess organ viability prior to transplantation and platform to investigate novel therapeutic interventions. However, the wide variability in donor and graft characteristics between individual donor livers limits the comparability of results. We investigated the hypothesis that the development of a split liver machine perfusion protocol provides the ideal comparative controls in the investigation of machine perfusion techniques and therapeutic interventions, thus leading to more comparable results. Four discarded human donor livers were surgically split following identification and separation of right and left inflow and outflow vessels. Each lobe, on separate perfusion machines, was subjected to normothermic perfusion using an artificial hemoglobin-based oxygen carrier solution for 6 h. Metabolic parameters as well as hepatic artery and portal vein perfusion parameters monitored. Trends in hepatic artery and portal vein flows showed a general increase in both lobes throughout each perfusion experiment, even when normalized for tissue weight. Progressive decreases in perfusate lactate and glucose levels exhibited comparable trends in between lobes. Our results demonstrate comparability between right and left lobes when simultaneously subjected to normothermic machine perfusion. In the pre-clinical setting, this model provides the ideal comparative controls in the investigation of therapeutic interventions.

摘要

供体肝脏机器灌注是一种在移植前评估器官活力的有前景的工具,也是一个用于研究新型治疗干预措施的平台。然而,个体供体肝脏之间供体和移植物特征的广泛差异限制了结果的可比性。我们研究了这样一个假设,即开发一种劈离式肝脏机器灌注方案可为机器灌注技术和治疗干预措施的研究提供理想的对照,从而得出更具可比性的结果。在识别并分离左右流入和流出血管后,对四个废弃的人类供体肝脏进行手术劈离。每个肝叶在单独的灌注机器上,使用基于人工血红蛋白的氧载体溶液进行6小时的常温灌注。监测代谢参数以及肝动脉和门静脉灌注参数。肝动脉和门静脉血流趋势显示,在每个灌注实验过程中,两个肝叶的血流总体上均有所增加,即使按组织重量进行标准化后也是如此。灌注液中乳酸和葡萄糖水平的逐渐下降在两个肝叶之间呈现出可比的趋势。我们的结果表明,左右肝叶在同时进行常温机器灌注时具有可比性。在临床前环境中,该模型为治疗干预措施的研究提供了理想的对照。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca50/7925992/68ff05b215f1/fsurg-08-627332-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca50/7925992/8e54d191e1a0/fsurg-08-627332-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca50/7925992/bc46db7b4baa/fsurg-08-627332-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca50/7925992/15777b622148/fsurg-08-627332-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca50/7925992/3384206d5598/fsurg-08-627332-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca50/7925992/bc885d0e32fc/fsurg-08-627332-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca50/7925992/68ff05b215f1/fsurg-08-627332-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca50/7925992/8e54d191e1a0/fsurg-08-627332-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca50/7925992/bc46db7b4baa/fsurg-08-627332-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca50/7925992/15777b622148/fsurg-08-627332-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca50/7925992/3384206d5598/fsurg-08-627332-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca50/7925992/bc885d0e32fc/fsurg-08-627332-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca50/7925992/68ff05b215f1/fsurg-08-627332-g0006.jpg

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2
Manipulation of Lipid Metabolism During Normothermic Machine Perfusion: Effect of Defatting Therapies on Donor Liver Functional Recovery.常温机械灌注期间脂代谢的调控:去脂治疗对供体肝功能恢复的影响。
Liver Transpl. 2019 Jul;25(7):1007-1022. doi: 10.1002/lt.25439.
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Development of Clinical Criteria for Functional Assessment to Predict Primary Nonfunction of High-Risk Livers Using Normothermic Machine Perfusion.
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Ann Surg Open. 2022 Feb 3;3(1). doi: 10.1097/AS9.0000000000000124. eCollection 2022 Mar.
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Full-left-full-right split liver transplantation for adult recipients: a systematic review and meta-analysis.成人受者全肝离断-再分配肝移植:系统评价和荟萃分析。
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