The superior effect of the combination of FK 506 and deoxyspergualin on rat cardiac allograft survival.
In this present study, the effects of FK 506 and 15-deoxyspergualin (DSG), with respect to dose, timing, and combination, were investigated in an ACI-to-LEW rat cardiac allograft model. FK 506 was administered intramuscularly for 14 days starting on day 0 after grafting, while DSG was given intraperitoneally for 7 days starting on day 0,4, or 7 after transplantation. FK 506 or DSG monotherapy prolonged cardiac allograft survival in dose-dependent manners, and the minimum effective dose for overcoming rejection was 0.1 mg/kg per day in the case of FK 506 and 1.0 mg/kg per day for DSG. The graft survival rate was higher with administration of DSG starting on day 4 on day 0 after transplantation. A low dosage of FK 506 starting on day 0, in combination with DSG starting on day 0 or day 4 (but not on day 7), had a synergistic effect in prolonging allograft survival for 14.0 +/- 3.3 days and 25.4 +/- 8.2 days, respectively. The most effective combination treatment schedule for prolongation of allograft survival was FK 506 starting on day 0 and DSG starting on day 4 after transplantation.