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 fo r pancreas transplants, but study models have been difficult to develo p. In a rat model that allows study of acute rejection to the exclusio n of nonspecific effects of transplant surgery on the pancreas, in vit ro synthesis of prostacyclin (PGI(2)) and thromboxane A(2) (TXA(2)) by transplanted pancreas and the blood vessels transplanted with it was measured using an RIA for their stable hydrolysis products 6-keto-pros taglandin F-1a and thromboxane B-2 (TXB(2)). TXB(2) synthesis was sign ificantly greater in allotransplanted pancreas than isotransplanted pa ncreas from the 5th day after transplantation. Rejection was complete in the allografted group 7-9 days after transplantation. 6-Keto-prosta glandin F-1a synthesis was similar in the pancreas for both allografts and isografts. Similar changes were seen in aorta, celiac artery, sup erior mesenteric artery, and portal vein transplanted with the pancrea s. In the transplanted aorta, TXB(2) was significantly greater in the allograft group from the third posttransplant day. A group of CsA-trea ted allografts sampled after 9 days had transplanted pancreatic parenc hymal and vascular prostanoid synthesis in the isograft range. The cha nges in PGI(2) and TXA(2) synthesis that accompany cellular rejection may mediate vascular failure in rejecting pancreas transplants, and ch anges in PGI(2) and TXA(2) synthesis in blood vessels transplanted wit h the pancreas could promote early vascular thrombosis.