Westerkamp Andrie C, Karimian Negin, Matton Alix P M, Mahboub Paria, van Rijn Rianne, Wiersema-Buist Janneke, de Boer Marieke T, Leuvenink Henri G D, Gouw Annette S H, Lisman Ton, Porte Robert J
1 Surgical Research Laboratory, Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. 2 Section of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. 3 Department of Pathology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Transplantation. 2016 Apr;100(4):825-35. doi: 10.1097/TP.0000000000001081.
The mechanism through which oxygenated hypothermic machine perfusion (HMP) improves viability of human extended criteria donor (ECD) livers is not well known. Aim of this study was to examine the benefits of oxygenated HMP after static cold storage (SCS).
Eighteen ECD livers that were declined for transplantation underwent ex situ viability testing using normothermic (37 °C) machine perfusion (NMP) after traditional SCS (0 °C-4 °C) for 7 to 9 hours. In the intervention group (n = 6), livers underwent 2 hours of oxygenated HMP (at 12 °C) after SCS and before NMP. Twelve control livers underwent NMP without oxygenated HMP after SCS.
During HMP, hepatic ATP content increased greater than 15-fold, and levels remained significantly higher during the first 4 hours of NMP in the HMP group, compared with controls. Cumulative bile production and biliary secretion of bilirubin and bicarbonate were significantly higher after HMP, compared with controls. In addition, the levels of lactate and glucose were less elevated after HMP compared with SCS preservation alone. In contrast, there were no differences in levels of hepatobiliary injury markers AST, ALT, LDH, and gamma-GT after 6 hours of NMP. Hepatic histology at baseline and after 6 hours of NMP revealed no differences in the amount of ischemic necrosis between both groups.
Two hours of oxygenated HMP after traditional SCS restores hepatic ATP levels and improves hepatobiliary function but does not reduce (preexisting) hepatobiliary injury in ECD livers.
氧合低温机器灌注(HMP)改善人类边缘供体(ECD)肝脏存活能力的机制尚不清楚。本研究的目的是探讨静态冷保存(SCS)后氧合HMP的益处。
18例被拒绝移植的ECD肝脏在传统SCS(0℃-4℃)7至9小时后,采用常温(37℃)机器灌注(NMP)进行体外存活能力测试。在干预组(n = 6)中,肝脏在SCS后和NMP前接受2小时的氧合HMP(12℃)。12例对照肝脏在SCS后接受无氧合HMP的NMP。
在HMP期间,肝脏ATP含量增加超过15倍,与对照组相比,HMP组在NMP的前4小时内水平仍显著更高。与对照组相比,HMP后胆汁累积生成以及胆红素和碳酸氢盐的胆汁分泌显著更高。此外,与单独SCS保存相比,HMP后乳酸和葡萄糖水平升高较少。相比之下,NMP 6小时后肝胆损伤标志物AST、ALT、LDH和γ-GT水平没有差异。基线时和NMP 6小时后的肝脏组织学显示两组之间缺血坏死量没有差异。
传统SCS后2小时的氧合HMP可恢复肝脏ATP水平并改善肝胆功能,但不会减轻ECD肝脏(已存在的)肝胆损伤。