Organ Transplant Centre, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, China.
Transplantation. 2023 May 1;107(5):e139-e151. doi: 10.1097/TP.0000000000004529. Epub 2023 Apr 22.
Ischemia-free liver transplantation (IFLT) has been innovated to avoid graft ischemia during organ procurement, preservation, and implantation. However, the metabolism activity of the donor livers between in the in situ and ex situ normothermic machine perfusion (NMP) conditions, and between standard criteria donor and extend criteria donor remains unknown.
During IFLT, plasma samples were collected both at the portal vein and hepatic vein of the donor livers in situ during procurement and ex situ during NMP. An ultra-high performance liquid chromatography-mass spectrometry was conducted to investigate the common and distinct intraliver metabolite exchange.
Profound cysteine and methionine metabolism, and aminoacyl-tRNA biosynthesis were found in both in situ and ex situ conditions. However, obvious D-arginine and D-ornithine metabolism, arginine and proline metabolism were only found in the in situ condition. The suppressed activities of the urea cycle pathway during ex situ condition were confirmed in an RNA expression level. In addition, compared with extend criteria donor group, standard criteria donor group had more active intraliver metabolite exchange in metabonomics level. Furthermore, we found that the relative concentration of p-cresol, allocystathionine, L-prolyl-L-proline in the ex situ group was strongly correlated with peak alanine aminotransferase and aspartate aminotransferase at postoperative days 1-7.
In the current study, we show the common and distinct metabolism activities during IFLT. These findings might provide insights on how to modify the design of NMP device, improve the perfusate components, and redefine the criteria of graft viability.
无缺血肝移植（IFLT）的创新在于避免器官获取、保存和植入过程中的供肝缺血。然而，在原位和体外常温机器灌注（NMP）条件下以及在标准标准供体和扩展标准供体之间，供体肝脏的代谢活性仍不清楚。
在 IFLT 期间，在供体肝脏的原位采集门静脉和肝静脉的血浆样本，在原位采集门静脉和肝静脉的血浆样本，并进行超高效液相色谱-质谱分析，以研究常见和独特的肝内代谢物交换。
在原位和体外条件下均发现了明显的半胱氨酸和蛋氨酸代谢以及氨酰-tRNA 生物合成。然而，只有在原位条件下才发现明显的 D-精氨酸和 D-鸟氨酸代谢、精氨酸和脯氨酸代谢。在 RNA 表达水平上证实了体外条件下尿素循环途径活性受到抑制。此外，与扩展标准供体组相比，标准标准供体组在代谢组学水平上具有更活跃的肝内代谢物交换。此外，我们发现，在体外组中 p-甲酚、allocystathionine、L-脯氨酰-L-脯氨酸的相对浓度与术后第 1-7 天的峰值丙氨酸氨基转移酶和天冬氨酸氨基转移酶强烈相关。
在本研究中，我们展示了 IFLT 期间的共同和独特代谢活动。这些发现可能为如何改进 NMP 设备的设计、改进灌流液成分以及重新定义移植物活力标准提供了思路。
