I-2190A is a potent immunosuppressive drug for vascularized heart transplantation in rats

Abstract

The effect of a new immunosuppressant-I-2190A was tested in a rodent heart allograft model. Grafts were transplanted to recipients heterotopically. There were 5 groups: group 1 received no immunosuppressive agents; group 2 was given CsA (2. 0 mg/kg, i. p.); group 3 was administered I-2190A (0. 1 mg/ kg, i. p.) in carboxymethyl cellulose (CMC); group 4 received injection of I-2190A (0. 5 mglkg, i. p. in CMC)) group 5 received the combination treatment of I-2190A (0. 1 mglkg) and CsA (2. 0 mglkg). Immunosuppressants were discontinued 14 days after operation. No statistically significant difference in grafts median survival time (MST) was found between group 2 (9. 5 days) and group 1 (9 days). The MSTs of grafts in group 3 (22 days,P< 0. 05), group 4 (> 100 days,P<0. 01) and group 5 (> 100 days,P<0. 01) were significantly prolonged compared with control group 1 (9 days). Our results suggest that I-2190A is a potent immunosuppressant able to significantly prolong heart allograft survival in rats after a short time treatment. Low-dose I-2190A could potentiate the effect of sub-therapeutic dose of CsA as well.

Keywords

I-2190A / immunosuppressant / allotransplantation

References

[1] StepkowskiS M, ChenH F, DalozeP, et al.. Prolongation by rapamycin of heart, kidney, pancreas, and small bowel allograft survival in rats. Transplant Proc, 1991, 23: 507-507

[2] AlmondP S, MossA M, NakhlehR E, et al.. Rapamycin: immunosuppression, hyporesponsiveness, and side effects in a porcine renal allograft model. Transplantation, 1993, 56: 275-275

[3] ChenZ H, HeO C, ZhongM Y, et al.. Modification of heterotopic heart allografting in rats. Chinese Journal Of Transplantation, 1982, 3: 38-38

[4] The International Society for Heart Transplantation. A working formulation for the standardization of nomenclature in the diagnosis of heart and lung rejection: heart rejection study group. J Heart Transplantation, 1990, 9: 587-587

[5] Molar-KimberK L. Mechanism of action of rapamycin. Transplant Proc, 1996, 28: 964-964