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PROLONGATION OF RAT CARDIAC ALLOGRAFT SURVIVAL BY THEATMENT WITH PROSTACYCLIN OR ASPIRIN DURING ACUTE REJECTION

Hearts taken from DA (RT1a) rats were transplanted heterotopically to PVG (RT1c) rats of the same sex (day 0). On day 1 or on day 5 rats were treated with proetacyclin (PGI2), 250 ng/kg/min, by continuous infusion of alkaline solution into the inferior vena cava until the time of rejection. Controls received glycine buffer infusion alone, from day 1 or day 5. Cessation of palpable graft beat was taken as the end point of rejection. When PGI2 was infused from day 5 median graft survival time was prolonged from a control of 7.8 days to 9.3 days (P < 0.05). When PGI2 was infused from day 1, graft survival time was prolonged from a control of 7.4 days to 8.6 days (P < 0.05). Other groups of rats were treated from day 1 or from day 5 with aspirin (acetylsalicylic acid), 200 mg/kg/day, by 8-hourly subcutaneous injection in saline. Control groups received saline alone. When aspirin was given from day 5, graft survival time was prolonged from a control of 7.3 days to 9.5 days (P < 0.05). When aspirin was given from day 1 graft survival time was prolonged from a control of 7.2 days to 14.9 days (P < 0.01), and in two cases this led to very prolonged survival. Histological examination at the time of rejection showed lymphocyte and neutrophil infiltration to be much more prominent than vessel occlusion in all groups. These results imply that PGI2 and aspirin may be beneficial to graft survival in acute rejection, but this is not due to reduced occlusion of blood vessels by platelets.