EFFECT OF A SHORT-COURSE OF RAPAMYCIN, CYCLOSPORINE-A, AND DONOR-SPECIFIC TRANSFUSION ON RAT CARDIAC ALLOGRAFT SURVIVAL

The interactions of rapamycin (Rapa), CsA, and donor-specific transfus ion (DST) were examined in an ACI to Lewis rat heterotopic cardiac all ograft model. Survival data were truncated at 175 days for the purpose of statistical comparisons. Vehicle (Veh)-treated animals rejected at a mean of 7.3+/-0.2 days. Treatment with a DST on the day before tran splantation (d-1) resulted in a decreased survival of 5.5+/-0.3 days ( P<0.05). An 8-day course of low-dose CsA (d-1 to d6) in Veh-treated an imals prolonged allograft survival to 10.3+/-0.5 days (P<0.05). The ad dition of a DST d-1 to the Veh/CsA-treated animals resulted in a syner gistic prolongation of survival to 45.7+/-12.5 days (P<0.05). Rapa pro ved to be a potent immunosuppressive agent in this model, with an 8-da y course of Rapa (d-1 to d6) at 0.5 mg/kg/day (R1) or 1.5 mg/kg/day (R 2), resulting in mean allograft survivals of 24.2+/-5.0 and 67.3+/-20. 9 days, respectively (P<0.05 vs. Veh or Veh/CsA). Rapa demonstrated sy nergy with CsA by further prolonging allograft survival to 115.9+/-27. 9 days (R1/CsA, P<0.05 vs. Veh/CsA, R1) and 164.6+/-10.4 days (R2/CsA, P<0.05 vs. Veh/CsA). The extended graft survival using a combination of Rapa and DST, compared to Rapa alone, did not prove to be statistic ally significant. When all three treatments were combined (Rapa/DST/Cs A), no significant benefit to survival was seen over Veh/DST/CsA (45.7 +/-12.5 days vs. R1/DST/CsA, 81.9+/-18.4 days; R2/DST/CsA, 98.5+/-21.3 days; P>0.05). If Rapa was withheld until postoperative day 1 (Rapa, 1.5 mg/kg/day on d1 to d6/DST/CsA), enhancement of the DST/CsA effect was seen with a mean survival of 170.2+/-4.8 days (P<0.05). This sugge sts that the timing of Rapa administration may significantly impact it s interaction with DST/CsA treatment and merits further investigation.