Control of the structural and functional consequences of vein graft intimal hyperplasia with a 21-aminosteroid--U74389G.

Following angioplasty and vein bypass grafting, there is endothelial cell injury, infiltration of leukocytes and smooth muscle cell (SMC) proliferation leading to intimal hyperplasia which may result in stenosis and can lead to eventual occlusion. This study examines the effect of the 21-aminosteroid U74389G (Upjohn Company), on the formation of vein graft intimal hyperplasia in vivo and on SMC DNA synthesis and proliferation in vitro. Twenty New Zealand White rabbits had a right carotid interposition bypass graft using the ipsilateral external jugular vein. Ten animals received chronic oral therapy with U74389G (25 mg/kg/day; begun 5 days before surgery and continued until harvest) and 10 control animals received vehicle only. All animals were sacrificed on the 28th postoperative day. Vein grafts were harvested either for histology/videomorphometry (n = 6 per group) or for in vitro isometric tension studies (n = 4; four 5 mm rings per graft). The incorporation of [3H]thymidine into the cellular DNA of serum-stimulated rabbit aortic SMC (passage 6th to 12th) was assessed in the presence of increasing concentrations of U74389G (10(-9) to 10(-4) M). The effect of U74389G on in vitro cell proliferation was also assessed. Treatment with U74389G produced a 44% decrease in overall mean intimal thickness from 82 +/- 1 microM (mean +/- S.E.M.) in the controls to 57 +/- 10 microM in the U74389G treated vein grafts (p = 0.003).(ABSTRACT TRUNCATED AT 250 WORDS)