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. Nontransplant vascular injury models have shown that angiotensin converting enzyme (ACE) inhibitors reduce myointimal proliferation and preserve lumen 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 observed without captopril administration after heterotopic cardiac transplantation, and the other 19 rats (group 2) were administered captopril (50 mg/kg per day in drinking water) after heart transplantation. Graft 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 significantly 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 rejection) were also significantly higher in group 1 than those in group 2 both at 3 months (grades, 2.3 +/- 0.7 vs 0.9 +/- 0.9; P < .05) and 6 months (grades, 3.0 +/- 0.9 vs 0.9 +/- 0.3; P < .01) after transplantation. The cardiac allographs in group 2 showed minimal intimal proliferation, intact elastic laminae, and reduced smooth muscle cell proliferation.

Conclusions: These results suggest that the ACE inhibitor captopril may be effective in prevention of accelerated graft CAD.