RAMIPRIL AND EXPERIMENTAL VEIN GRAFT INTIMAL HYPERPLASIA

Angiotensin-converting enzyme (ACE) inhibitors have been shown to redu ce the intimal proliferation in animal models of arterial angioplasty and vein bypass grafting. This study examines the effect of high-dose ramipril, an ACE inhibitor that does not contain a sulfhydryl group, o n the development of intimal hyperplasia in experimental vein bypass g rafts. Twenty New Zealand White rabbits underwent common carotid inter position bypass grafting. Twelve were treated with ramipril (2mg/kg/da y; po) five days prior to surgery and thereafter until harvest. The re maining 8 animals were used as controls. Vein grafts were harvested at twenty-eight days by pressure fixation (80 mmHg). The grafts were sec tioned into proximal, middle, and distal thirds, and the thickness of the intima and the media and the area of the lumen from each segment w ere determined by videomorphometry. The effect of ramipril on the [H3] thymidine incorporation into DNA of serum-stimulated smooth muscle cel ls (culture passage 6 to 12) was also assessed. There was a 50% mortal ity rate in the rabbits that received ramipril, and this was assumed t o be related to the high dose of the drug. Ramipril treatment reduced mean vein graft intimal area by 34% (P > 0.05), but this was accompani ed by an increase of 73% in the mean medial area of the vein grafts as compared with controls. These changes resulted in a decrease in the m ean intimal ratio (intima/[intima + media]) by 39% in the ramipril gro up as compared with controls. Ramipril did not inhibit [H3]thymidine i ncorporation into DNA of serum-stimulated smooth muscle cells. This st udy shows that treatment with the nonsulfhydryl ACE inhibitor ramipril , even at a high dose, produces only a marginal reduction in the forma tion of intimal hyperplasia in experimental vein grafts.