Takada Y, Taniguchi H, Fukunaga K, Yuzawa K, Otsuka M, Todoroki T, Iijima T, Fukao K
Department of Surgery, Tsukuba University, Japan.
Surgery. 1998 Jun;123(6):692-8.
Prolonged warm ischemic injury in non-heart-beating donors (NHBDs) significantly affects hepatic allograft function after liver transplantation (LTx).
The effects of FK506 and the platelet activating factor antagonist E5880 on postoperative function of hepatic allografts procured from NHBDs were evaluated in porcine orthotopic LTx. In donors, livers were subjected to 90 minutes of warm ischemia and a subsequent 4-hour cold preservation. Group 1 (n = 6) was the untreated control group. In group 2 (n = 4), donors were pretreated with FK506 (0.3 mg/kg). In group 3 (n = 4), donors and recipients were treated with E5880 (0.3 mg/kg). In group 4 (n = 6), pigs were treated with both FK506 and E5880.
All of the recipients in group 1 died within 12 hours. In groups 2 and 3, half of the recipients survived more than 12 hours. In group 4, all of the recipients survived more than 2 days (p < 0.01 compared with group 1). The improved survival seen in group 4 was associated with a reduction in the serum concentrations of glutamic oxaloacetic transaminase and lactate, and a restoration of hepatic energy charge.
The present study suggests that FK506 and E5880 can improve the function of hepatic allografts subjected to prolonged warm ischemia in NHBDs, and that the protective effects of the two drugs seem to be synergistic.
非心脏跳动供体（NHBDs）的长时间热缺血损伤显著影响肝移植（LTx）后肝移植功能。
在猪原位肝移植中评估FK506和血小板活化因子拮抗剂E5880对从NHBDs获取的肝移植术后功能的影响。在供体中，肝脏经历90分钟热缺血及随后4小时冷保存。第1组（n = 6）为未治疗对照组。第2组（n = 4），供体用FK506（0.3 mg/kg）预处理。第3组（n = 4），供体和受体用E5880（0.3 mg/kg）治疗。第4组（n = 6），猪同时用FK506和E5880治疗。
第1组所有受体在12小时内死亡。第2组和第3组，一半受体存活超过12小时。第4组，所有受体存活超过2天（与第1组相比，p < 0.01）。第4组观察到的存活率提高与血清谷草转氨酶和乳酸浓度降低以及肝能量电荷恢复有关。
本研究表明FK506和E5880可改善NHBDs中经历长时间热缺血的肝移植功能，且两种药物的保护作用似乎具有协同性。
