Beneficial effect of donor pretreatment with thromboxane A2 synthase inhibitor on the graft survival in pig liver transplantation.
With a known evidence that thromboxane A2 (TxA2) is elevated in the perfusate of the liver transplant (LTx) recipient, TxA2 is likely to play a role in the pathogenesis of preservation reperfusion injury. In this study, effectiveness of donor pretreatment with TxA2 synthase inhibitor, sodium ozagrel (SO), in the prevention of primary nonfunction (PNF) was investigated. LTx was performed for eight pigs which received the grafts treated with SO during harvest surgery (treatment group). Eight other animals were the control group. All of the animals in the treatment group survived longer than 7 days, whereas 37.5% (three of eight) of the control group died from PNF within 3 days postoperative. Significantly lower serum LDH levels were noted in the treatment group than control. Serum thromboxane B2 (TxB2) and 6-keto-PGF1 alpha were both elevated in the control group. However, a significant decrease in TxB2 was noted in the treatment group after reperfusion of the liver graft. Polymorphonuclear leukocyte (PMN) infiltration in the graft after reperfusion was significantly greater in the control group than in the treatment group. Hepatocyte microsteatosis was prominent in the control group after reperfusion. Donor pretreatment with SO was effective in the prevention of PNF after LTx. The beneficial effects of this drug are improvement in microcirculation allowing better perfusion of cold preservative and the blocking effect of platelet-PMN-endothelial interaction which is thought to be a primary etiology in reperfusion injury.
Yokoyama
I
I
Nagoya University, School of Medicine, Department of Surgery II, Japan.
Negita
M
M
Kobayashi
T
T
Hayashi
S
S
Hachisuka
T
T
Sato
E
E
Orihara
A
A
Uchida
K
K
Takagi
H
H
D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood; D000818:Animals; D006085:Graft Survival; D008099:Liver / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D016031:Liver Transplantation; D008689:Methacrylates / Q000494:pharmacology*; D009926:Organ Preservation; D013552:Swine; D013929:Thromboxane B2 / Q000378:metabolism; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors*; D014019:Tissue Donors
D008689:Methacrylates; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D013930:Thromboxane-A Synthase; C034364:ozagrel