Prolonged hepatic warm ischemia in non-heart-beating donors: protective effects of FK506 and a platelet activating factor antagonist in porcine liver transplantation.
BACKGROUND
Prolonged warm ischemic injury in non-heart-beating donors (NHBDs) significantly affects hepatic allograft function after liver transplantation (LTx).


METHODS
The effects of FK506 and the platelet activating factor antagonist E5880 on postoperative function of hepatic allografts procured from NHBDs were evaluated in porcine orthotopic LTx. In donors, livers were subjected to 90 minutes of warm ischemia and a subsequent 4-hour cold preservation. Group 1 (n = 6) was the untreated control group. In group 2 (n = 4), donors were pretreated with FK506 (0.3 mg/kg). In group 3 (n = 4), donors and recipients were treated with E5880 (0.3 mg/kg). In group 4 (n = 6), pigs were treated with both FK506 and E5880.


RESULTS
All of the recipients in group 1 died within 12 hours. In groups 2 and 3, half of the recipients survived more than 12 hours. In group 4, all of the recipients survived more than 2 days (p < 0.01 compared with group 1). The improved survival seen in group 4 was associated with a reduction in the serum concentrations of glutamic oxaloacetic transaminase and lactate, and a restoration of hepatic energy charge.


CONCLUSIONS
The present study suggests that FK506 and E5880 can improve the function of hepatic allografts subjected to prolonged warm ischemia in NHBDs, and that the protective effects of the two drugs seem to be synergistic.
Takada
Y
Y
Department of Surgery, Tsukuba University, Japan.
Taniguchi
H
H
Fukunaga
K
K
Yuzawa
K
K
Otsuka
M
M
Todoroki
T
T
Iijima
T
T
Fukao
K
K
D000255:Adenosine Triphosphate / Q000032:analysis; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007511:Ischemia / Q000503:physiopathology*; D008099:Liver / Q000098:blood supply* / Q000187:drug effects / Q000473:pathology; D016031:Liver Transplantation; D010880:Piperidines / Q000494:pharmacology*; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors*; D011726:Pyridinium Compounds / Q000494:pharmacology*; D013552:Swine; D016559:Tacrolimus / Q000494:pharmacology*
D007166:Immunosuppressive Agents; D010880:Piperidines; D010972:Platelet Activating Factor; D011726:Pyridinium Compounds; C072429:E 5880; D000255:Adenosine Triphosphate; D001219:Aspartate Aminotransferases; D016559:Tacrolimus