Effect of combined use of aminoguanidine and cyclosporine A on acute rejection following cardiac allograft in rats

Abstract

Objective To study the effect of the combined use of aminoguanidine (AG) and cyclosporine A (CsA) on acute rejection following cardiac allograft. Methods Except the control group, all other three groups were respectively treated by AG 600mg/kg every day subcutaneously 0 to 7 days after transplantation, low-dose CsA 2mg/kg every day i.m 0 to 7 days after transplantation, and low-dose CsA plus AG. Inducible nitric oxide synthase (iNOS) expression and nitric oxide (NO) production during acute allograft rejection were detected at 4th day after operation, and the graft survival was observed.Results Compared with the control group, iNOS expression and NO production were significantly inhibited in the AG-treated group (P＜0.05)，the progression of acute rejection was slightly attenuated and allografted heart survival prolonged. The inhibitory effects of iNOS activity and NO production in the recipients receiving the combined treatment of low-dose CsA plus AG were higher than those receiving low-dose CsA alone. Compared with the low-dose CsA group, low-dose CsA plus AG could significantly reduce the histologic grade of acute rejection (P＜0.01) and prolong the graft survival (P＜0.05). Conclusion The combined use of low-dose CsA and AG could synergistically suppress iNOS activity and NO production, and significantly prolong allografted heart survival.