Effect of a new immunosuppressant, 15-deoxyspergualin, on heterotopic rat heart transplantation, in comparison with cyclosporine.

Abstract

In this study, 15-deoxyspergualin (DSG) or cyclosporine (CsA) was administered to heterotopically heart-grafted rats for 15 days, commencing on the day of transplantation. In addition, a 31P nuclear magnetic resonance (NMR) technique was applied to investigate the in vivo energy metabolism of the graft. A significant prolongation of graft survival was observed in groups treated with 2.5 mg/kg and 5 mg/kg of DSG, when compared with the control group not treated with an immunosuppressant. One graft in the DSG 2.5 mg/kg-treated group and one in the 5 mg/kg-treated group survived for more than 100 days after grafting. The 31P NMR study demonstrated that, although rejection occurred in the rats treated with 2.5 mg/kg of DSG during the early period after transplantation, 5 mg/kg of DSG inhibited rejection completely. As for CsA, while 2 mg/kg of the drug did not affect graft survival, 5 mg/kg and 14 mg/kg significantly prolonged survival. It was revealed by 31P NMR, however, that CsA 5 mg/kg did not quite inhibit rejection by itself, and 14 mg/kg of CsA, which was the tolerogenic dose, exerted a cardiotoxic effect. In consequence, DSG seems to be a powerful immunosuppressant with a low toxic effect.