End-ischemic machine perfusion reduces bile duct injury in donation after circulatory death rat donor livers independent of the machine perfusion temperature
End-ischemic machine perfusion reduces bile duct injury in donation after circulatory death rat donor livers independent of the machine perfusion temperature
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DOI：
10.1002/lt.24200
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发表时间：
2015-10-01
影响因子：
4.6
通讯作者：
Porte, Robert J.
中科院分区：
文献类型：
--
作者：
Westerkamp, Andrie C.;Mahboub, Paria;Porte, Robert J.
静冷贮藏（SCS）后短时间的氧机灌注（MP）可减少心脏死亡（DCD）供肝捐献时的胆道损伤。然而，保护胆管的理想灌注温度尚不清楚。本研究评估了保护胆管的最佳灌注温度。用SCS保存DCD大鼠肝脏6小时。此后，在低温机器灌注、亚常温机器灌注或可控氧合再暖（COR）条件下进行1小时的氧合MP。随后，在2小时常温非原位再灌注期间评估移植物和胆管活力。在MP研究组中，与SCS相比，测量了较低水平的转氨酶、乳酸脱氢酶（LDH）和硫代巴比妥酸活性物质。同时，线粒体耗氧量和三磷酸腺苷（ATP）的产生在MP组中显著增加。胆道功能的生物标志物，包括胆汁生成、胆道碳酸氢盐浓度和pH值，在MP组中显著升高，而胆道上皮损伤的生物标志物（胆道γ -谷氨酰转移酶[GGT]和LDH）在MP保存的肝脏中显著降低。组织学分析显示，与SCS相比，MP组大胆管上皮损伤较小。综上所述，与SCS相比，DCD肝脏终末缺血氧合MP可以更好地保存胆道上皮功能和形态，而与MP进行时的温度无关。终末缺血氧合MP可减轻DCD肝移植术后胆道损伤。
A short period of oxygenated machine perfusion (MP) after static cold storage (SCS) may reduce biliary injury in donation after cardiac death (DCD) donor livers. However, the ideal perfusion temperature for protection of the bile ducts is unknown. In this study, the optimal perfusion temperature for protection of the bile ducts was assessed. DCD rat livers were preserved by SCS for 6 hours. Thereafter, 1 hour of oxygenated MP was performed using either hypothermic machine perfusion, subnormothermic machine perfusion, or with controlled oxygenated rewarming (COR) conditions. Subsequently, graft and bile duct viability were assessed during 2 hours of normothermic ex situ reperfusion. In the MP study groups, lower levels of transaminases, lactate dehydrogenase (LDH), and thiobarbituric acid reactive substances were measured compared to SCS. In parallel, mitochondrial oxygen consumption and adenosine triphosphate (ATP) production were significantly higher in the MP groups. Biomarkers of biliary function, including bile production, biliary bicarbonate concentration, and pH, were significantly higher in the MP groups, whereas biomarkers of biliary epithelial injury (biliary gamma-glutamyltransferase [GGT] and LDH), were significantly lower in MP preserved livers. Histological analysis revealed less injury of large bile duct epithelium in the MP groups compared to SCS. In conclusion, compared to SCS, end-ischemic oxygenated MP of DCD livers provides better preservation of biliary epithelial function and morphology, independent of the temperature at which MP is performed. End-ischemic oxygenated MP could reduce biliary injury after DCD liver transplantation.