Department of General, Vascular and Pediatric Surgery, University of Saarland, Homburg/Saar, Germany.
Am J Surg. 2012 Feb;203(2):168-76. doi: 10.1016/j.amjsurg.2011.01.026. Epub 2011 Jul 22.
Graft dysfunction of steatotic livers (SL) still remains a major challenge in liver transplantation. Different mechanisms are thought to be involved in the impaired tolerance of SL to ischemia-reperfusion injury. Thus, different pharmacologic strategies may need to be combined to effectively protect SL and to reduce graft dysfunction after transplantation. Therefore, we analyzed the effectiveness of a multidrug donor preconditioning (MDDP) procedure to protect SL from cold ischemia-reperfusion injury.
Liver steatosis was induced by a high-carbohydrate, fat-free diet. A total of 24 Sprague-Dawley rats were divided into 3 groups (n = 8 each), including a control group with nonsteatotic livers (Con), a vehicle-treated SL group (SL-Con), and a SL group undergoing MDDP (SL-MDDP), including pentoxyphylline, glycine, deferoxamine, N-acetylcysteine, erythropoietin, melatonin, and simvastatin. MDDP was applied before liver perfusion with 4°C histidine-tryptophan-ketoglutarate (HTK) solution and organ harvest. After 24 hours of cold storage in HTK, postischemic reperfusion was performed in an isolated liver reperfusion model using 37°C Krebs-Henseleit bicarbonate buffer.
After 60 minutes of reperfusion, SL showed a significant reduction of bile flow as well as a marked increase of liver enzyme levels and apoptotic cell death compared with Con. This was associated with an increased malondialdehyde formation, interleukin-1 production, and leukocytic tissue infiltration. MDDP completely abolished the inflammatory response and was capable of significantly reducing parenchymal dysfunction and injury.
MDDP decreases SL injury after cold storage and reperfusion. The concept of MDDP as a simple and safe preoperative regime, thus may be of interest in clinical use, expanding the donor pool from marginal donors.
脂肪变性肝脏（SL）的移植物功能障碍仍然是肝移植的主要挑战。不同的机制被认为参与了 SL 对缺血再灌注损伤的耐受受损。因此，可能需要结合不同的药物治疗策略来有效保护 SL 并减少移植后的移植物功能障碍。因此，我们分析了多药物供体预处理（MDDP）程序保护 SL 免受冷缺血再灌注损伤的有效性。
通过高碳水化合物、无脂肪饮食诱导肝脂肪变性。总共 24 只 Sprague-Dawley 大鼠分为 3 组（每组 n = 8），包括非脂肪变性肝脏的对照组（Con）、接受vehicle 处理的 SL 组（SL-Con）和接受 MDDP 的 SL 组（SL-MDDP），包括己酮可可碱、甘氨酸、去铁胺、N-乙酰半胱氨酸、促红细胞生成素、褪黑素和辛伐他汀。MDDP 在 4°C 组氨酸-色氨酸-酮戊二酸（HTK）溶液灌注和器官收获前应用于肝脏。在 HTK 中冷储存 24 小时后，在离体肝再灌注模型中使用 37°C Krebs-Henseleit 碳酸氢盐缓冲液进行缺血后再灌注。
再灌注 60 分钟后，与 Con 相比，SL 胆汁流量明显减少，肝酶水平和凋亡细胞死亡显著增加。这与丙二醛形成、白细胞介素-1 产生和白细胞组织浸润增加有关。MDDP 完全消除了炎症反应，并能够显著降低实质功能障碍和损伤。
MDDP 可减少 SL 冷储存和再灌注后的损伤。MDDP 作为一种简单、安全的术前方案的概念，因此可能在临床上具有应用价值，扩大了边缘供体的供体库。
