Transplant Division, Department of Surgery, University of Massachusetts, Worcester, MA.
Transplant Center, Massachusetts General Hospital, Harvard University, Boston, MA.
Transplantation. 2019 Feb;103(2):363-370. doi: 10.1097/TP.0000000000002530.
Donation after circulatory death (DCD) liver grafts are known to be predisposed to primary nonfunction and ischemic cholangiopathy. Many DCD grafts are discarded because of older donor age or long warm ischemia times. Thus, it is critical to improve the quality of DCD liver grafts. Here, we have tested whether an enriched oxygen carrier added to the preservation solution can prolong graft survival and reduce biliary damage.
We assessed the adenosine triphosphate (ATP) content decay of mouse liver grafts after cold ischemia, warm ischemia, and combined warm+cold ischemia. In addition, we used a rat model of liver transplantation to compare survival of DCD grafts preserved in high-oxygen solution (preoxygenated perfluorocarbon [PFC] + University of Wisconsin [UW] solution) versus lower oxygen solution (preoxygenated UW solution).
Adenosine triphosphate levels under UW preservation fall to less than 10% after 30 minutes of warm ischemia. Preoxygenated UW solution with PFC reached a significantly higher PaO2. After 45 minutes of warm ischemia in oxygenated UW + PFC solution, grafts showed 63% higher levels of ATP (P = 0.011). In addition, this was associated with better preservation of morphology when compared to grafts stored in standard UW solution. Animals that received DCD grafts preserved in higher oxygenation solution showed improved survival: 4 out of 6 animals survived long-term whereas all control group animals died within 24 hours.
The additional oxygen provided by PFC during static cold preservation of DCD livers can better sustain ATP levels, and thereby reduce the severity of ischemic tissue damage. PFC-based preservation solution extends the tolerance to warm ischemia, and may reduce the rate of ischemic cholangiopathy.
已证实,循环死亡后(DCD)供体的肝脏移植物容易发生原发性无功能和缺血性胆管病。由于供体年龄较大或热缺血时间较长,许多 DCD 移植物被丢弃。因此,提高 DCD 肝脏移植物的质量至关重要。在此,我们研究了在保存液中添加富含氧气载体是否可以延长移植物的存活时间并减少胆管损伤。
我们评估了小鼠冷缺血、热缺血和联合冷热缺血后肝移植物三磷酸腺苷(ATP)含量的衰减情况。此外,我们使用大鼠肝移植模型比较了在高氧溶液(预充氧全氟化碳[PFC]+威斯康星大学[UW]溶液)和低氧溶液(预充氧 UW 溶液)中保存的 DCD 移植物的存活率。
在 UW 保存下,经过 30 分钟的热缺血后,ATP 水平降至 10%以下。含有 PFC 的预充氧 UW 溶液达到了显著更高的 PaO2。在富含氧 UW+PFC 溶液中进行 45 分钟的热缺血后,移植物的 ATP 水平提高了 63%(P=0.011)。此外,与在标准 UW 溶液中保存的移植物相比,这种方法保存的移植物形态也更好。接受在高氧合溶液中保存的 DCD 移植物的动物显示出更好的生存:6 只动物中有 4 只长期存活,而所有对照组动物在 24 小时内死亡。
在 DCD 肝脏的静态冷保存过程中,PFC 提供的额外氧气可以更好地维持 ATP 水平,从而减轻缺血性组织损伤的严重程度。基于 PFC 的保存溶液延长了对热缺血的耐受,可能减少缺血性胆管病的发生率。