Liver preservation with machine perfusion and a newly developed cell-free oxygen carrier solution under subnormothermic conditions.
Liver preservation with machine perfusion and a newly developed cell-free oxygen carrier solution under subnormothermic conditions.
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DOI：
10.1111/ajt.12991
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发表时间：
2015-02
期刊：
影响因子：
--
通讯作者：
Marsh JW
中科院分区：
文献类型：
--
作者：
Fontes P;Lopez R;van der Plaats A;Vodovotz Y;Minervini M;Scott V;Soltys K;Shiva S;Paranjpe S;Sadowsky D;Barclay D;Zamora R;Stolz D;Demetris A;Michalopoulos G;Marsh JW
我们描述了一种新的保存模式，将低温条件（21°C）下的机器灌注（MP）与新的血红蛋白氧载体（HBOC）溶液相结合。在猪原位肝移植中，在冷缺血9小时和5天随访后，将MP（n = 6）与冷静态保存（CSP; n = 6）进行比较。在肝脏保存前、保存中和保存后收集受体的外周血、连续肝活检、保存液和胆汁标本。除了线粒体功能测定、转录组学、代谢组学和炎症介质分析之外，还进行了临床实验室和组织学分析。与CSP相比，MP动物具有：（1）显著较高的存活率（100% vs. 33%; p < 0.05）;（2）上级移植功能（p < 0.05）;（3）肝脏O2输送量是O2消耗量的8倍（0.78 mL O2/g/h vs. 0.096 mL O2/g/h）;（4）胆汁生成量显著增加（MP = 378.5 ± 179.7; CS = 151.6 ± 116.85）。MP下调肝组织中的干扰素（IFN）-α和IFN-γ。MP同种异体移植物在再灌注后清除乳酸，产生尿素，维持再生并产生亲水性胆汁。在亚常温条件下增强的氧合触发再生和细胞保护反应，从而改善同种异体移植物功能。与CSP相比，在21°C下使用HBOC溶液的MP显著改善了肝脏保存。作者在猪肝移植模型中比较了21°C下无细胞氧载体溶液的机器灌注与冷藏保存，并证明了有效的离体氧合在5天内对肝移植功能的显著影响。
We describe a new preservation modality combining machine perfusion (MP) at subnormothermic conditions (21°C) with a new hemoglobin‐based oxygen carrier (HBOC) solution. MP (n = 6) was compared to cold static preservation (CSP; n = 6) in porcine orthotopic liver transplants after 9 h of cold ischemia and 5‐day follow‐up. Recipients' peripheral blood, serial liver biopsies, preservation solutions and bile specimens were collected before, during and after liver preservation. Clinical laboratorial and histological analyses were performed in addition to mitochondrial functional assays, transcriptomic, metabolomic and inflammatory mediator analyses. Compared with CSP, MP animals had: (1) significantly higher survival (100% vs. 33%; p < 0.05); (2) superior graft function (p < 0.05); (3) eight times higher hepatic O2 delivery than O2 consumption (0.78 mL O2/g/h vs. 0.096 mL O2/g/h) during MP; and (4) significantly greater bile production (MP = 378.5 ± 179.7; CS = 151.6 ± 116.85). MP down‐regulated interferon (IFN)‐α and IFN‐γ in liver tissue. MP allografts cleared lactate, produced urea, sustained gluconeogenesis and produced hydrophilic bile after reperfusion. Enhanced oxygenation under subnormothermic conditions triggers regenerative and cell protective responses resulting in improved allograft function. MP at 21°C with the HBOC solution significantly improves liver preservation compared to CSP. The authors compare machine perfusion with a cell‐free oxygen carrier solution at 21°C with cold storage preservation in a porcine liver transplant model and demonstrate the significant impact of effective ex vivo oxygenation for liver allograft function over a 5‐day period.
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影响因子：
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