Effect of 15-deoxyspergualin on accelerated rejection in rat heart transplantation

The effect of 15-deoxyspergualin (DSG) on accelerated rejection was evaluated using a rat heart transplantation model. Lewis rats (LEW, RT1l) served as the organ recipient and Brown Norway rats (BN, RT1n) as the donor. In the accelerated rejection model, the LEW recipient was sensitized with BN skin and BN heart was transplanted 7 days later; the heart graft was rejected within 2 days (n = 7). Histologically, the graft showed coagulation necrosis and hemorrhage throughout the myocardium. DSG (2.5 mg/kg/day) was administered to the recipient under the following three protocols: group 1: during the sensitization period (7 days); group 2: from 3 days after the sensitization to 2 days after grafting (7 days), and group 3: immediately after heart transplantation. The mean graft survival period in groups 1, 2, and 3 was 4.3 +/- 0.8 days (n = 7, p < 0.01 vs untreated host), 11.7 +/- 2.1 days (n = 7, p < 0.001, vs. untreated host), and 2.0 +/- 0 days (n = 6), respectively. The rejected grafts in groups 1 and 3 histologically showed coagulation necrosis and hemorrhage. By contrast, in group 2, the major histological change was interstitial lymphocyte infiltration and there were few findings such as coagulation necrosis or hemorrhage. In the complement-dependent cytotoxicity test, serum obtained at the second posttransplant day from the recipients treated in group 1 showed a high cytotoxicity level, although the cytotoxicity level of serum obtained from the recipients treated in group 2 was consistently low.(ABSTRACT TRUNCATED AT 250 WORDS)