LIBERATION OF VASOACTIVE SUBSTANCES AND ITS PREVENTION WITH THROMBOXANE A(2) SYNTHASE INHIBITOR IN PIG-LIVER TRANSPLANTATION

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 unde rlying pathophysiology, it is suspected that various vasoactive substa nces are liberated after reperfusion of the graft. In order to investi gate this matter? we conducted an experimental study with pig liver al lotransplantation. Two groups of animals received donor grafts with or without thromboxane synthase inhibitor (sodium ozagrel), 1.25 mg/kg b ody weight intravenously, given at the time of liver harvesting. All o f the recipient animals in the treatment group (n = 10) survived longe r than 7 days whereas three of ten animals in the control group died w ithin 7 days. Serum lactate dehydrogenase (LDH) in the recipient serum at 1 h after reperfusion was significantly lower in the treatment gro up (915.1 +/- 167.3 U/l) than in the control group (1264.4 +/- 134.7 U /l). Serum thromboxane B-2 (2261.7 +/- 1055.7 pg/ml) and endothelin-1 (6.3 +/- 2.2 pg/ml) after reperfusion in the treatment group were sign ificantly lower than those in the control group (4220.0 +/- 1711.0 pg/ ml and 11.2 +/- 3.1 pg/ml, respectively). Although serum angiotensin I I 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 recipie nts than no such treatment. We speculate that the inhibition of thromb oxane A(2) production suppresses the liberation of ether vasoconstrict ive substances, preventing microcirculatory disturbance and. thereby, contributing to improved graft function after liver transplantation.