Local delivery of 17-beta-estradiol decreases neointimal hyperplasia aftercoronary angioplasty in a porcine model

BACKGROUND Neointimal hyperplasia is an important mechanism of restenosis a fter percutaneous transluminal coronary angioplasty (PTCA). Systemically ad ministered estrogen is known to inhibit neointimal formation after arterial injury. OBJECTIVES We sought to assess the efficacy of locally delivered 17-beta-es tradiol (BE) in inhibiting neointimal hyperplasia after PTCA. METHODS Eighteen juvenile farm pigs were studied. Coronary angioplasty was performed in all three coronary arteries of each animal. After PTCA, each c oronary artery in each pig was randomized to receive either local delivery of 600 mug BE, vehicle alone or PTCA only. Twelve animals were euthanized a t 28 days for morphometric analysis, and four animals were euthanized at se ven days for immunohistochemical analysis of vascular smooth muscle cell (S MC) proliferative activity. Two animals died a few days after PTCA and were excluded. RESULTS On morphometric study, the arterial segments treated with BE demons trated significantly less neointimal proliferation. Arteries treated with B E had reductions in several indexes of restenosis compared with arteries tr eated with vehicle alone or PTCA only: neointimal area (0.4 +/- 0.09 mm(2) for BE vs. 1.14 +/- 0.33 mm(2) for vehicle alone vs. 0.88 +/- 0.2 mm(2) for PTCA only, p < 0.05), percent neointima (12.16 +/- 2.57% vs. 25.46 +/- 4.7 3% vs. 23.02 +/- 3.97%, p < 0.025), neointima/media area (0.59 +/- 0.14 vs. 1.75 +/- 0.41 vs. 1.67 +/- 0.43, p < 0.01) and restenotic index (1.3 +/- 0 .14 vs. 2.42 +/- 0.22 vs. 2.4 +/- 0.23, p < 0.005). Immunohistochemistry sh owed decreased SMC proliferative activity in BE-treated arteries compared w ith the other two treatment groups (p < 0.05). CONCLUSIONS Local delivery of BE significantly decreases neointimal hyperpl asia after PTCA in pigs, probably by the inhibition of SMC proliferation. ( C) 2000 by the American College of Cardiology.