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 orthotopic liver transplantation model in Lewis rats with portal reperfusion only. No significant recipient endotoxemia, TNF-alpha release, or mortality occurred in control recipients following transplantation from normal donors. The doses of endotoxin needed to kill 50% and 100% of animals after hepatic artery ligation were, respectively, 4 mg/kg and 10 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 +/- 2.5 x 10(3) endotoxin unit/ml (EU/ml), P < 0.01), 45 min (8.8 +/- 1.1 x 10(3) EU/ml, P < 0.001) and 8 hr (18.5 +/- 3.5 x 10(3) EU/ml, P < 0.001) 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 graft reperfusion the resistance to endotoxin administration was significantly 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 reduces the recipient resistance to endotoxin with subsequent increase in mortality.
Azoulay
D
D
Paul Brousse Hospital, Villejuif, France.
Astarcioglu
I
I
Lemoine
A
A
Dennison
A
A
Mathieu
D
D
Saulnier
C
C
Chatenoud
L
L
Reynès
M
M
Bismuth
H
H
D000818:Animals; D004731:Endotoxins / Q000008:administration & dosage*; D006085:Graft Survival / Q000187:drug effects*; D008099:Liver / Q000473:pathology; D016031:Liver Transplantation / Q000276:immunology* / Q000401:mortality*; D008168:Lung / Q000473:pathology; D008297:Male; D051381:Rats; D011917:Rats, Inbred Lew; D014185:Transplantation, Isogeneic; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D004731:Endotoxins; D014409:Tumor Necrosis Factor-alpha