Beneficial effect of thromboxane A2 synthetase inhibitor (OKY-046) on 24-hr simple hypothermic preservation of the canine pancreas graft.
This study was performed to investigate the potential protective effect of OKY-046, an inhibitor of thromboxane A2 synthetase, on the viability of 24-hr preserved canine segmental pancreas graft. Each graft was preserved in either cold Euro-Collins (E-C) solution (control group; n = 5) or E C+OKY-046(10(-4)M) solution (OKY-046 group; n = 5). In both groups, grafts were preserved for 24 hr and calculated the total levels of 6keto-prostaglandin F1 alpha (6ket-PGF1 alpha) and thromboxane B2(TxB2) in the preservation solution per pancreas graft weight at the time point of 0,3,7,12,24 hr after preservation. The efficacy of OKY-046 in protecting ischemically stressed grafts was examined by histological findings of the grafts before transplantation and blood flow of the transplanted pancreas graft. During 24-hr preservation time, increased production of 6ket-PGF1 alpha and decreased production of TxB2 were found in OKY-046 group. Histologically ischemic damage of the acinar cells was observed in the control group, but it was milder in the OKY-046 group. The blood flow of the transplanted pancreas in the OKY-046 group were higher than that in control group. In the OKY-046 group, all dogs survived with functioning grafts, although some grafts were lost in the control group. These results suggest that there is a possibility that OKY-046 may contribute to the improvement of the survival rate in segmental pancreas transplantation.
Nagami
H
H
First Department of Surgery, Shimane Medical University, Izumo, Japan.
Tamura
K
K
Kin
S
S
Teramoto
M
M
Ishida
T
T
D000818:Animals; D002470:Cell Survival; D004285:Dogs; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D005260:Female; D008297:Male; D008689:Methacrylates / Q000627:therapeutic use*; D008833:Microcirculation; D009926:Organ Preservation; D016035:Pancreas Transplantation / Q000502:physiology; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors*
D004791:Enzyme Inhibitors; D008689:Methacrylates; D013930:Thromboxane-A Synthase; C034364:ozagrel