POTENTIAL OF ASPIRIN TO INHIBIT THROMBOTIC MICROANGIOPATHY IN GALT-KO PIG HEARTS AFTER TRANSPLANTATION INTO BABOONS

Abstract

O474 Aim: To assess survival of GalT-KO pig heart transplants in baboons. Methods: Eight baboons received induction therapy with anti-thymocyte globulin, thymic irradiation (n=7), cobra venom factor from days -1 to 14 (n=2) or days -1 to 3 (n=3), and maintenance therapy with a human anti-human CD154 mAb, mycophenolate mofetil, and methylprednisolone. Heparin was administered to all baboons. Group 1 (n=3) received heparin alone. Group 2 (n=3) received additional antithrombin (days 1-12), one of which subsequently received aspirin. Group 3 (n=2) received additional aspirin (40mg p.o. alt days). Results: Group 1 hearts developed a thrombotic microangiopathy (TM); two ceased functioning (days 59 and 67), and one baboon died of hemorrhage (day 56). All Group 2 hearts developed discrete myocardial infarctions, and all showed TM; one was euthanized for anemia on day 23, and in two the graft stopped functioning (days 78 and 110), one with TM plus rejection. One Group 3 baboon was euthanized for an ischemic leg (day 16) with a beating heart, and one remains with a beating heart (day 145); neither shows TM. A rise in serum troponin T always accompanied the development of TM. While full immunosuppressive therapy was being administered, cellular infiltration of the grafts was minimal or absent, the mixed lymphocyte reaction to pig cells was unresponsive, and no elicited antibody was detected. The graft that is still functioning well at >145 days is the longest survival of a pig organ in a nonhuman primate recorded to date. Conclusions: Rejection (including hyperacute, acute humoral, and cellular) can largely be prevented in GalT-KO pig hearts, but TM develops. This appears to be inhibited by a combination of heparin and aspirin.