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  • Title: Effect of single-dose rapamycin-based immunosuppression on the development of cardiac allograft vasculopathy.
    Author: Goggins WC, Fisher RA, Cohen DS, Tawes JW, Grimes MM.
    Journal: J Heart Lung Transplant; 1996 Aug; 15(8):790-5. PubMed ID: 8878761.
    Abstract:
    BACKGROUND: Cardiac allograft vasculopathy is the major cause of graft loss more than 1 year after transplantation. Daily rapamycin dosing has been shown to inhibit arterial intimal thickening caused by both alloimmune and mechanical injury. The combination of a single preoperative dose of rapamycin with a short (7 day) course of cyclosporine A has been shown to extend cardiac allograft survival, but its effects on the development of cardiac allograft vasculopathy has not been reported. METHODS: The ACI (RT1(a)) to Lewis (RT1(1)) heterotopic cardiac allograft model was used to assess the development of cardiac allograft vasculopathy and rejection. Treatment groups included nonimmunosuppressed control, cyclosporine A, cyclosporine A/donor-specific transfusion, and rapamycin/cyclosporine A. RESULTS: The addition of a single preoperative dose of rapamycin to a short course of cyclosporine A significantly reduced the prevalence of cardiac allograft vasculopathy in small (1.18 +/- 1.4 versus 0.05 +/- 0.3; p = 0.0001), medium (2.05 +/- 1.09 versus 0.26 +/- 0.62; p = 0.0001), and large (2.57 +/- 0.84 versus 1.43 +/- 1.2; p = 0.0008) vessels when compared with that in allografts treated with a single preoperative donor-specific transfusion and the same cyclosporine A schedule. Cardiac allograft vasculopathy did not develop in the nonimmunosuppressed control grafts or the group treated with cyclosporine A alone, because of the short survival times in these groups. In addition, there was a reduction of the rejection score in the rapamycin-treated allografts compared with that in the other treatment groups (4.0 +/- 0.0 versus 3.25 +/- 0.5; p = 0.0006). CONCLUSIONS: These results suggest that a single preoperative dose of rapamycin is efficacious in preventing the development of cardiac allograft vasculopathy, and continued immunosuppression with rapamycin may be unnecessary.
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