Thromboxane and prostacyclin synthesis in experimental pancreas transplantation. Changes in parenchymal and vascular prostanoids.
The principal causes of failure of a pancreas transplant are rejection and vascular thrombosis. There is an unusually high attrition rate for pancreas transplants, but study models have been difficult to develop. In a rat model that allows study of acute rejection to the exclusion of nonspecific effects of transplant surgery on the pancreas, in vitro synthesis of prostacyclin (PGI2) and thromboxane A2 (TXA2) by transplanted pancreas and the blood vessels transplanted with it was measured using an RIA for their stable hydrolysis products 6-keto-prostaglandin F1 alpha and thromboxane B2 (TXB2). TXB2 synthesis was significantly greater in allotransplanted pancreas than isotransplanted pancreas from the 5th day after transplantation. Rejection was complete in the allografted group 7-9 days after transplantation. 6-Keto-prostaglandin F1 alpha synthesis was similar in the pancreas for both allografts and isografts. Similar changes were seen in aorta, celiac artery, superior mesenteric artery, and portal vein transplanted with the pancreas. In the transplanted aorta, TXB2 was significantly greater in the allograft group from the third posttransplant day. A group of CsA-treated allografts sampled after 9 days had transplanted pancreatic parenchymal and vascular prostanoid synthesis in the isograft range. The changes in PGI2 and TXA2 synthesis that accompany cellular rejection may mediate vascular failure in rejecting pancreas transplants, and changes in PGI2 and TXA2 synthesis in blood vessels transplanted with the pancreas could promote early vascular thrombosis.
Johnson
B F
BF
Transplant-Urology Laboratories, Royal Hallamshire Hospital, Sheffield, UK.
Thomas
G
G
Wiley
K N
KN
Greaves
M
M
Preston
F E
FE
Fox
M
M
Raftery
A T
AT
D015121:6-Ketoprostaglandin F1 alpha / Q000096:biosynthesis; D000208:Acute Disease; D000818:Animals; D001011:Aorta / Q000378:metabolism; D002445:Celiac Artery / Q000378:metabolism / Q000637:transplantation; D016572:Cyclosporine / Q000627:therapeutic use; D011464:Epoprostenol / Q000096:biosynthesis*; D006084:Graft Rejection / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism; D008297:Male; D017538:Mesenteric Artery, Superior / Q000378:metabolism / Q000637:transplantation; D010179:Pancreas / Q000098:blood supply / Q000378:metabolism; D016035:Pancreas Transplantation / Q000009:adverse effects / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D013927:Thrombosis / Q000209:etiology / Q000517:prevention & control; D013928:Thromboxane A2 / Q000096:biosynthesis*; D013929:Thromboxane B2 / Q000096:biosynthesis; D014184:Transplantation, Homologous; D014185:Transplantation, Isogeneic; D014682:Vena Cava, Inferior / Q000378:metabolism
D013929:Thromboxane B2; D013928:Thromboxane A2; D015121:6-Ketoprostaglandin F1 alpha; D016572:Cyclosporine; D011464:Epoprostenol