Protecting the viability of hepatic allografts procured from non-heart-beating donors by blockade of endothelin and platelet activating factor in porcine liver transplantation.
OBJECTIVE
The function of hepatic allograft from non-heartbeating donors (NHBD) is significantly affected by warm ischemic injury before harvesting.


METHODS
The effects of the endothelin (ET) antagonist TAK-044 and the platelet activating factor (PAF) antagonist E5880 on the function of grafts from NHBD were evaluated in a porcine orthotopic liver transplantation. The liver grafts were subjected to 90 min of warm ischemia and 4 hours cold preservation. Group 1 (n = 4; n is the number of donor/recipient pairs) was used as a control (untreated). In group 2 (n = 4), donors and recipients were treated with TAK-044 (3 mg/kg). In group 3 (n = 4), pigs were treated with E5880 (0.3 mg/kg). In group 4 (n = 4), pigs were treated with TAK-044 and E5880.


RESULTS
The 7 day survival rate of the recipients in groups 1, 2, 3 and 4 was 0, 25, 25 and 100%, respectively (p<0.05, group 1 versus 4). The increases of the serum concentrations of aspartate transaminase, lactate dehydrogenase and arterial lactate 1-4 hours after transplantation were significantly inhibited in the treated groups.


CONCLUSIONS
The blockade of ET and PAF has protective effects on the function of hepatic grafts from NHBD.
Fukunaga
K
K
Department of Surgery, Institute of Clinical Medicine, Tsukuba University, Tsukuba City, Ibaraki, Japan.
Takada
Y
Y
Taniguchi
H
H
Yuzawa
K
K
Otsuka
M
M
Todoroki
T
T
Goto
K
K
Fukao
K
K
D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D016232:Endothelins / Q000037:antagonists & inhibitors*; D007770:L-Lactate Dehydrogenase / Q000097:blood; D019344:Lactic Acid / Q000097:blood; D008099:Liver / Q000098:blood supply / Q000473:pathology; D008102:Liver Circulation / Q000187:drug effects; D016031:Liver Transplantation; D010456:Peptides, Cyclic / Q000494:pharmacology*; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors*; D015427:Reperfusion Injury / Q000517:prevention & control*; D013552:Swine; D013997:Time Factors; D014019:Tissue Donors; D014184:Transplantation, Homologous
D016232:Endothelins; D010456:Peptides, Cyclic; D010972:Platelet Activating Factor; C088196:TAK 044; D019344:Lactic Acid; D007770:L-Lactate Dehydrogenase; D001219:Aspartate Aminotransferases