THE EFFECTS OF DONOR AND RECIPIENT ENDOTOXEMIA ON TNF-ALPHA PRODUCTION AND MORTALITY IN THE RAT MODEL OF SYNGENIC ORTHOTOPIC LIVER-TRANSPLANTATION

The effects of administration of endotoxin to donors or recipients on the mortality rate, evolution of endotoxin levels, and tumor necrosis factor alpha (TNF-alpha) release were investigated in a syngenic ortho topic liver transplantation model in Lewis rats with portal reperfusio n only. No significant recipient endotoxemia, TNF-alpha release, or mo rtality occurred in control recipients following transplantation from normal donors. The doses of endotoxin needed to kill 50% and 100% of a nimals after hepatic artery ligation were, respectively, 4 mg/kg and 1 0 mg/kg. Transplantation of animals' livers with no preservation phase from donors who were administered a lethal dose of endotoxin for this combination (10 mg/kg) produced significant recipient endotoxemia at 10 min (6.9+/-2.5x10(3) endotoxin unit/ml (EU/ml), P<0.01), 45 min (8. 8+/-1.1x10(3) EU/ml, P<0.001) and 8 hr (18.5+/-3.5x10(3) EU/ml, P<0.00 1) after graft reperfusion. Significant levels of TNF-alpha were also detected in these animals at 45 min (280+/-70 pg/ml, P<0.007) and 8 hr (80+/-40 pg/ml, P<0.05) when compared with the controls. Mortalities in recipients of OLT from donor animals that had received endotoxin (2 mg/kg or 4 mg/kg) immediately prior to the harvesting procedure was 0 % and 20%, respectively, compared with no death in the control group. When recipient animals were administered endotoxin immediately after g raft reperfusion the resistance to endotoxin administration was signif icantly reduced compared with animals that had not received OLT (LD50 <2 mg/kg versus 4 mg/kg; LD100 4 mg/kg versus 10 mg/kg, respectively). These results show that endotoxin and its effects can be transferred from the liver graft donor to the recipient and that OLT per se reduce s the recipient resistance to endotoxin with subsequent increase in mo rtality.