Yokoyama I, Kobayashi T, Negita M, Hayashi S, Yasutomi M, Katayama A, Uchida K, Takagi H
Nagoya University, School of Medicine, Department of Surgery II, Japan.
Transpl Int. 1996;9(1):76-81. doi: 10.1007/BF00336816.
There are multiple causes of liver graft nonfunction in the early post-transplant period. Since a severe microcirculatory disturbance based on ischemia-reperfusion liver injury is considered to be the main underlying pathophysiology, it is suspected that various vasoactive substances are liberated after reperfusion of the graft. In order to investigate this matter, we conducted an experimental study with pig liver allotransplantation. Two groups of animals received donor grafts with or without thromboxane synthase inhibitor (sodium ozagrel), 1.25 mg/ kg body weight intravenously, given at the time of liver harvesting. All of the recipient animals in the treatment group (n = 10) survived longer than 7 days whereas three of ten animals in the control group died within 7 days. Serum lactate dehydrogenase (LDH) in the recipient serum at 1 h after reperfusion was significantly lower in the treatment group (915.1 +/- 167.3 U/l) than in the control group (1264.4 +/- 134.7 U/l). Serum thromboxane B2 (2261.7 +/- 1055.7 pg/ml) and endothelin-1 (6.3 +/- 2.2 pg/ml) after reperfusion in the treatment group were significantly lower than those in the control group (4220.0 +/- 1711.0 pg/ml and 11.2 +/- 3.1 pg/ml, respectively). Although serum angiotensin II after reperfusion tended to be lower in the treatment group than in the controls serum renin activity was less than 3 ng/ml in both groups of animals. There were no differences in the plasma endotoxin levels between the two groups. We conclude that the administration of sodium ozagrel to the donor animals provided better graft function in recipients than no such treatment. We speculate that the inhibition of thromboxane A2 production suppresses the liberation of other vasoconstrictive substances, preventing microcirculatory disturbance and, thereby, contributing to improved graft function after liver transplantation.
肝移植术后早期肝移植无功能有多种原因。由于基于缺血再灌注肝损伤的严重微循环障碍被认为是主要的潜在病理生理学机制，因此怀疑移植肝再灌注后会释放各种血管活性物质。为了研究此事，我们进行了猪肝同种异体移植的实验研究。两组动物在肝脏获取时静脉注射1.25 mg/kg体重的血栓素合酶抑制剂（奥扎格雷钠），一组接受，另一组不接受。治疗组（n = 10）的所有受体动物存活时间超过7天，而对照组的十只动物中有三只在7天内死亡。再灌注后1小时受体血清中的血清乳酸脱氢酶（LDH）在治疗组（915.1 +/- 167.3 U/l）显著低于对照组（1264.4 +/- 134.7 U/l）。治疗组再灌注后的血清血栓素B2（2261.7 +/- 1055.7 pg/ml）和内皮素-1（6.3 +/- 2.2 pg/ml）显著低于对照组（分别为4220.0 +/- 1711.0 pg/ml和11.2 +/- 3.1 pg/ml）。虽然治疗组再灌注后的血清血管紧张素II往往低于对照组，但两组动物的血清肾素活性均小于3 ng/ml。两组之间的血浆内毒素水平没有差异。我们得出结论，给供体动物施用奥扎格雷钠比不进行这种治疗能为受体提供更好的移植肝功能。我们推测，抑制血栓素A2的产生可抑制其他血管收缩物质的释放，防止微循环障碍，从而有助于改善肝移植后的移植肝功能。
