CAPTOPRIL REDUCES GRAFT CORONARY-ARTERY DISEASE IN A RAT HETEROTOPIC TRANSPLANT MODEL

Background. Transplant coronary artery disease (CAD) is characterized by severe myointimal proliferation causing vascular stenosis. Nontrans plant vascular injury models have shown that angiotensin converting en zyme (ACE) inhibitors reduce myointimal proliferation and preserve lum en integrity. We examined the effect of the ACE inhibitor captopril on graft CAD in a Lewis to F344 rat heterotopic cardiac transplantation model. Methods and Results. Twenty-five control rats (group 1) were ob served without captopril administration after heterotopic cardiac tran splantation, and the other 19 rats (group 2) were administered captopr il (50 mg/kg per day in drinking water) after heart transplantation. G raft survival 3 months after transplantation was significantly (P<.02) higher in group 2 (18 of 19, 95%) than that in group 1 (16 of 25, 64% ). Cellular rejection grades of the heart allografts were significantl y higher in group 1 than those in group 2 both at 3 months (grades, 2. 5+/-0.4 vs 1.3+/-0.7; P<.01) and 6 months (grades, 2.4+/-0.9 vs 0.8+/- 0.5; P<.05) after transplantation. The grades of graft CAD (vascular r ejection) were also significantly higher in group 1 than those in grou p 2 both at 3 months (grades, 2.3+/-0.7 vs 0.9+/-0.9; P<.05) and 6 mon ths (grades, 3.0+/-0.9 vs 0.9+/-0.3; P<.01) after transplantation. The cardiac allografts in group 2 showed minimal intimal proliferation, i ntact elastic laminae, and reduced smooth muscle cell proliferation. C onclusions. These results suggest that the ACE inhibitor captopril may be effective in prevention of accelerated graft CAD.