Op den Dries Sanna, Sutton Michael E, Karimian Negin, de Boer Marieke T, Wiersema-Buist Janneke, Gouw Annette S H, Leuvenink Henri G D, Lisman Ton, Porte Robert J
Section of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands ; Surgical Research Laboratory, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Section of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
PLoS One. 2014 Feb 14;9(2):e88521. doi: 10.1371/journal.pone.0088521. eCollection 2014.
Livers derived from donation after circulatory death (DCD) are increasingly accepted for transplantation. However, DCD livers suffer additional donor warm ischemia, leading to biliary injury and more biliary complications after transplantation. It is unknown whether oxygenated machine perfusion results in better preservation of biliary epithelium and the peribiliary vasculature. We compared oxygenated hypothermic machine perfusion (HMP) with static cold storage (SCS) in a porcine DCD model.
After 30 min of cardiac arrest, livers were perfused in situ with HTK solution (4°C) and preserved for 4 h by either SCS (n = 9) or oxygenated HMP (10°C; n = 9), using pressure-controlled arterial and portal venous perfusion. To simulate transplantation, livers were reperfused ex vivo at 37°C with oxygenated autologous blood. Bile duct injury and function were determined by biochemical and molecular markers, and a systematic histological scoring system.
After reperfusion, arterial flow was higher in the HMP group, compared to SCS (251±28 vs 166±28 mL/min, respectively, after 1 hour of reperfusion; p = 0.003). Release of hepatocellular enzymes was significantly higher in the SCS group. Markers of biliary epithelial injury (biliary LDH, gamma-GT) and function (biliary pH and bicarbonate, and biliary transporter expression) were similar in the two groups. However, histology of bile ducts revealed significantly less arteriolonecrosis of the peribiliary vascular plexus in HMP preserved livers (>50% arteriolonecrosis was observed in 7 bile ducts of the SCS preserved livers versus only 1 bile duct of the HMP preserved livers; p = 0.024).
Oxygenated HMP prevents arteriolonecrosis of the peribiliary vascular plexus of the bile ducts of DCD pig livers and results in higher arterial flow after reperfusion. Together this may contribute to better perfusion of the bile ducts, providing a potential advantage in the post-ischemic recovery of bile ducts.
循环死亡后捐赠（DCD）的肝脏越来越多地被接受用于移植。然而，DCD肝脏会遭受额外的供体热缺血，导致移植后胆管损伤和更多的胆道并发症。目前尚不清楚氧合机器灌注是否能更好地保存胆管上皮和胆管周围血管系统。我们在猪DCD模型中比较了氧合低温机器灌注（HMP）和静态冷藏（SCS）。
心脏骤停30分钟后，用HTK溶液（4°C）对肝脏进行原位灌注，并通过SCS（n = 9）或氧合HMP（10°C；n = 9）保存4小时，采用压力控制的动脉和门静脉灌注。为模拟移植，肝脏在37°C下用氧合自体血进行体外再灌注。通过生化和分子标志物以及系统的组织学评分系统来确定胆管损伤和功能。
再灌注后，HMP组的动脉血流量高于SCS组（再灌注1小时后分别为251±28和166±28 mL/min；p = 0.003）。SCS组肝细胞酶的释放明显更高。两组中胆管上皮损伤（胆管乳酸脱氢酶、γ-谷氨酰转移酶）和功能（胆管pH值和碳酸氢盐以及胆管转运蛋白表达）的标志物相似。然而，胆管组织学显示，HMP保存的肝脏中胆管周围血管丛的小动脉坏死明显较少（SCS保存的肝脏中有7条胆管观察到>50%的小动脉坏死，而HMP保存的肝脏中只有1条胆管；p = 0.024）。
氧合HMP可防止DCD猪肝脏胆管周围血管丛的小动脉坏死，并在再灌注后导致更高的动脉血流量。这两者共同作用可能有助于胆管更好地灌注，为胆管缺血后恢复提供潜在优势。
