Effects of platelet-activating factor antagonist on preservation/reperfusion injury of the graft in porcine orthotopic liver transplantation.
To investigate the role of platelet-activating factor (PAF) in the preservation/reperfusion injury of the liver graft, the effect of treatment with a potent PAF antagonist (E5880) was evaluated in a pig orthotopic liver transplantation model. The graft liver was flushed out and preserved for 8 hr at 4 degrees C using a simplified University of Wisconsin solution. The PAF antagonist was administered into the University of Wisconsin solution (1 mg/L), into the rinsing solution (1 mg/L), and to a recipient pig (0.3 mg/kg d.i.v.) in group 1. The PAF antagonist was not given in the control group (group 2). Postoperative survival of more than 12 hr was 100% (9/9) in group 1 and 56% (5/9) in group 2 (P < 0.05). At 12 hr after reperfusion of the graft (RPF), the arterial ketone body ratio (acetoacetate to 3-hydroxybutyrate) increased to 1.54 +/- 0.15 (mean +/- SEM) in group 1, compared with 0.95 +/- 0.09 (P < 0.05) in group 2. In group 2, blood leukocyte count decreased to 8.3 +/- 0.9 (x 10(3)/microliters) at 2 hr after RPF, in contrast to a slight increase in group 1 (14.3 +/- 1.8 x 10(3)/microliter, P < 0.01). At 4 hr after RPF, glutamic oxaloacetic transaminase (461 +/- 59 vs. 712 +/- 97 U/L, P < 0.05), glutamic pyruvic transaminase (65 +/- 4 vs. 82 +/- 5 U/L, P < 0.05), and the lactate level (6.2 +/- 1.1 vs. 9.4 +/- 1.0 mmol/L, P < 0.05) in arterial blood were significantly lower in group 1 than in group 2. Light and electron microscopic study at 1 hr after RPF showed neutrophil sludging in the sinusoids and sinusoidal endothelial cell damage in group 2, while these findings were attenuated in group 1. It is suggested that PAF plays a key role in microcirculatory disturbance of the liver graft manifested on reperfusion, and that the treatment with E5880 has a protective effect against preservation/reperfusion injury of the graft in liver transplantation.
Laboratoire de Chirurgie Experimentale, Fondation Transplantation, Strasbourg, France.
Y
Y
Takada
K
K
Boudjema
D
D
Jaeck
M
M
Bel-Haouari
M
M
Doghmi
M P
MP
Chenard
P
P
Wolf
J
J
Cinqualbre
D000241:Adenosine; D000493:Allopurinol; D000818:Animals; D005978:Glutathione; D006084:Graft Rejection / Q000517:prevention & control*; D007328:Insulin; D007958:Leukocyte Count; D008099:Liver / Q000098:blood supply* / Q000378:metabolism; D016031:Liver Transplantation; D008854:Microscopy, Electron; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism; D019188:Organ Preservation Solutions; D010880:Piperidines / Q000494:pharmacology*; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors*; D011726:Pyridinium Compounds / Q000494:pharmacology*; D011887:Raffinose; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D013552:Swine; D014021:Tissue Preservation; D000637:Transaminases / Q000097:blood
D007328:Insulin; D019188:Organ Preservation Solutions; D010880:Piperidines; D010972:Platelet Activating Factor; D011726:Pyridinium Compounds; C055206:University of Wisconsin-lactobionate solution; C072429:E 5880; D000493:Allopurinol; D000637:Transaminases; D005978:Glutathione; D000241:Adenosine; D011887:Raffinose