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EXPERIMENTAL STUDY

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

^a Department of Medicine, Montreal Heart Institute and University of Montreal, Montreal, Quebec, Canada

Manuscript received October 26, 1999; revised manuscript received May 17, 2000, accepted July 12, 2000.

Reprint requests and correspondence: Dr. Jean-François Tanguay, Montreal Heart Institute, Research Center, 5000 Belanger Street East, Montreal, Quebec, Canada H1T 1C8
tanguay{at}icm.umontreal.ca

BACKGROUND

Neointimal hyperplasia is an important mechanism of restenosis after percutaneous transluminal coronary angioplasty (PTCA). Systemically administered estrogen is known to inhibit neointimal formation after arterial injury.

OBJECTIVES

We sought to assess the efficacy of locally delivered 17-beta-estradiol (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 coronary artery in each pig was randomized to receive either local delivery of 600 µg BE, vehicle alone or PTCA only. Twelve animals were euthanized at 28 days for morphometric analysis, and four animals were euthanized at seven days for immunohistochemical analysis of vascular smooth muscle cell (SMC) proliferative activity. Two animals died a few days after PTCA and were excluded.

RESULTS

On morphometric study, the arterial segments treated with BE demonstrated significantly less neointimal proliferation. Arteries treated with BE had reductions in several indexes of restenosis compared with arteries treated with vehicle alone or PTCA only: neointimal area (0.4 ± 0.09 mm² for BE vs. 1.14 ± 0.33 mm² for vehicle alone vs. 0.88 ± 0.2 mm² for PTCA only, p < 0.05), percent neointima (12.16 ± 2.57% vs. 25.46 ± 4.73% 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 showed decreased SMC proliferative activity in BE-treated arteries compared with the other two treatment groups (p < 0.05).

CONCLUSIONS

Local delivery of BE significantly decreases neointimal hyperplasia after PTCA in pigs, probably by the inhibition of SMC proliferation.

Abbreviations and Acronyms   BE = 17-beta-estradiol   EEL = external elastic lamina   FL = fracture length   HPCD = 2-hydroxypropyl-beta-cyclodextrin   IEL = internal elastic lamina   PCNA = proliferating cell nuclear antigen   PTCA = percutaneous transluminal coronary angioplasty   SMC = smooth muscle cell

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