Effect of single-dose rapamycin-based immunosuppression on the development of cardiac allograft vasculopathy.
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.
Goggins
W C
WC
Department of Surgery, Medical College of Virginia/Virginia Commonwealth University, Richmond, 23298-0254, USA.
Fisher
R A
RA
Cohen
D S
DS
Tawes
J W
JW
Grimes
M M
MM
D000818:Animals; D003327:Coronary Disease / Q000188:drug therapy* / Q000473:pathology; D003331:Coronary Vessels / Q000187:drug effects* / Q000473:pathology; D016572:Cyclosporine / Q000008:administration & dosage; D006084:Graft Rejection / Q000473:pathology / Q000517:prevention & control*; D006085:Graft Survival / Q000187:drug effects*; D016027:Heart Transplantation / Q000276:immunology*; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D008297:Male; D011090:Polyenes / Q000008:administration & dosage*; D015995:Prevalence; D051381:Rats; D011912:Rats, Inbred ACI; D017208:Rats, Wistar; D020123:Sirolimus; D014184:Transplantation, Homologous
D007166:Immunosuppressive Agents; D011090:Polyenes; D016572:Cyclosporine; D020123:Sirolimus