Liberation of vasoactive substances and its prevention with thromboxane A2synthase inhibitor in pig liver transplantation

Abstract

Abstract 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 reper-fusion 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 dehy-drogenase (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). Sepm thromboxane B, (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 A, production suppresses the liberation of other vaso-constrictive substances, preventing microcirculatory disturbance and, thereby, contributing to improved graft function after liver transplantation.