Halofuginone, a specific collagen type I inhibitor, reduces anastomotic intimal hyperplasia.

OBJECTIVE: To determine if halofuginone hydrobromide, a specific type I collagen inhibitor, could prevent intimal hyperplasia at a vascular anastomosis. DESIGN: Intimal hyperplasia is characterized by smooth muscle cell proliferation and extracellular matrix accumulation. Halofuginone was used to block collagen production and smooth muscle cell proliferation in cell cultures and in a rabbit model of an end-to-end anastomosis of the right common carotid artery. Animals were fed a nontoxic dose of halofuginone. Eighteen rabbits were fed the inhibitor in a randomized blinded fashion and were examined after 4 weeks by harvesting the arteries after perfusion fixation at physiologic pressures. RESULTS: Halofuginone inhibited smooth muscle cell proliferation in vitro and had no effect on cell viability. Morphometric quantification verified that halofuginone treatment significantly attenuated anastomotic intimal thickness. CONCLUSION: Oral administration of halofuginone inhibits intimal hyperplasia at vascular anastomoses. Intimal hyperplasia inhibition by halofuginone may be a therapeutic option for preventing arterial stenosis in vascular surgery.