Sumimoto R, Lindell S L, Southard J H, Belzer F O
Department of Surgery, University of Wisconsin, Madison 53792.
Transplantation. 1992 Oct;54(4):610-4. doi: 10.1097/00007890-199210000-00008.
Many modifications of the UW solution have been reported to yield successful results in rat liver preservation and transplantation. One solution used histidine, in combination with lactobionate (HL-I), and gave superior preservation of the rat liver when compared with the UW solution. In this study we have compared the HL-I solution with 90 mM histidine, HL-II solution with 30 mM histidine, and the UW solution in dog liver preservation and transplantation. Dog livers were preserved for 48 hr in one of the three solutions and transplanted. The peak AST and ALT values were highest in livers preserved in HL-I, intermediate in UW solution, and lowest in HL-II. However, there were no significant differences among survival rates (average 5-7 days per group), posttransplant serum concentration of liver enzymes (AST, ALT, LDH, and alk-phos), clotting factors (PT and PTT), bilirubin, and fibrinogen concentration for each group. Dogs were sacrificed or died within 5-7 days due to rejection in nonimmunosuppressed dogs. Also, rat livers were preserved in the HL-II solution or in a solution in which histidine was replaced by isoleucine (IL-I). Isoleucine is an amino acid with a molecular mass similar to that of histidine, but is not as good a hydrogen ion buffer as histidine at the pH used for liver preservation (7.4). The buffer capacity of the IL-I solution was similar to the UW solution, but about one-half as much as the HL-II solution. Rats receiving a liver preserved for 30 hr in HL-II or IL-I were 100% viable. Rats receiving a liver preserved for 40-44 hr in HL-II or IL-I showed less survival (33% and 25%, respectively). This shows that histidine can be effectively replaced by isoleucine in a preservation solution and gives equivalent preservation results. Thus, the mechanism of improvement of liver preservation with histidine is not due to its action as a hydrogen ion buffer. These studies show that, although the HL solutions are superior for preservation of the rat liver, they are not superior to the UW solution for preservation of the dog liver. However, as others have shown in the rat liver transplant model, a simplified UW solution (HL-II) appears effective in dog liver preservation. The dog liver transplant model remains a more appropriate model for testing new preservation solutions prior to initiation of clinical trials.
据报道，UW溶液有许多改良版本在大鼠肝脏保存和移植中取得了成功。一种溶液使用组氨酸与乳糖酸（HL-I）结合，与UW溶液相比，对大鼠肝脏的保存效果更佳。在本研究中，我们将HL-I溶液（含90 mM组氨酸）、HL-II溶液（含30 mM组氨酸）与UW溶液用于犬肝脏的保存和移植，并进行了比较。犬肝脏在这三种溶液之一中保存48小时后进行移植。在HL-I溶液中保存的肝脏，其AST和ALT峰值最高，UW溶液中的居中，HL-II溶液中的最低。然而，各组的存活率（每组平均5 - 7天）、移植后血清肝酶（AST、ALT、LDH和碱性磷酸酶）浓度、凝血因子（PT和PTT）、胆红素及纤维蛋白原浓度之间并无显著差异。在未进行免疫抑制的犬中，犬在5 - 7天内由于排斥反应而被处死或死亡。此外，大鼠肝脏在HL-II溶液或组氨酸被异亮氨酸替代的溶液（IL-I）中保存。异亮氨酸是一种分子量与组氨酸相似的氨基酸，但在肝脏保存所用的pH值（7.4）下，其作为氢离子缓冲剂的效果不如组氨酸。IL-I溶液的缓冲能力与UW溶液相似，但约为HL-II溶液的一半。接受在HL-II或IL-I中保存30小时的肝脏的大鼠，存活率为100%。接受在HL-II或IL-I中保存40 - 44小时的肝脏的大鼠，存活率较低（分别为33%和25%）。这表明在保存溶液中异亮氨酸可以有效地替代组氨酸，并给出等效的保存效果。因此，组氨酸改善肝脏保存的机制并非因其作为氢离子缓冲剂的作用。这些研究表明，尽管HL溶液在大鼠肝脏保存方面更具优势，但在犬肝脏保存方面并不优于UW溶液。然而，正如其他人在大鼠肝脏移植模型中所表明的，一种简化的UW溶液（HL-II）在犬肝脏保存中似乎是有效的。在启动临床试验之前，犬肝脏移植模型仍然是测试新保存溶液的更合适模型。
