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Combined liver‐kidney perfusion enhances protective effects of normothermic perfusion on liver grafts from donation after cardiac death

机器灌注 医学 灌注 高架桥 肝移植 移植 冷库 肝损伤 肝细胞 内科学 男科 病理 生物 生物化学 园艺 体外
作者
Xiaoshun He,Fei Ji,Zhiheng Zhang,Yunhua Tang,Lu Yang,Shanzhou� Huang,Wenwen Li,Qiao Su,Wei Xiong,Zebin Zhu,Linhe Wang,Lei Lv,Jiyou Yao,Linan Zhang,Longjuan Zhang,Zhiyong Guo
出处
期刊:Liver Transplantation [Lippincott Williams & Wilkins]
卷期号:24 (1): 67-79 被引量:23
标识
DOI:10.1002/lt.24954
摘要

It has been shown that combined liver-kidney normothermic machine perfusion (NMP) is able to better maintain the circuit's biochemical milieu. Nevertheless, whether the combined perfusion is superior to liver perfusion alone in protecting livers from donation after circulatory death (DCD) is unclear. We aimed to test the hypothesis and explored the mechanisms. Livers from 15 DCD pig donors were subjected to either static cold storage (group A), liver-alone NMP (group B), or combined liver-kidney NMP (group C). Livers were preserved for 6 hours and reperfused ex vivo for 2 hours to simulate transplantation or were transplanted in situ. During perfusion, group C showed an improved acid-base and biochemical environment in the circuit over group B. After reperfusion, the architecture of the liver grafts was best preserved in group C, followed by group B, then group A, as shown by the histology and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling staining of both hepatocytes and biliary epithelium. Ki-67 staining showed substantial hepatocyte proliferation and biliary epithelial regeneration after perfusion in group B and group C. Group C produced more bile in the reperfusion phase than those in group A and group B, with more physiological bile composition and less severe biliary epithelium injury. Von Willebrand factor-positive endothelial cells and E-selectin expression decreased in both group B and group C. Combined liver-kidney NMP not only produced more adenosine triphosphate, protected the nitric oxide signaling pathway, but also diminished oxidative stress (high mobility group box-1 protein and 8-hydroxy-2-deoxy guanosine levels) and inflammatory cytokine (IL6 and IL8) release when compared with liver-alone NMP and CS. In addition, the 7-day survival rate of liver transplant recipients was higher in group C than that in groups A and B. In conclusion, combined liver-kidney NMP can better protect DCD livers from warm ischemia and reperfusion injury probably by maintaining the stability of the internal environment and by abolishing oxidative stress injury. Liver Transplantation 24 67-79 2018 AASLD.

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