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 mu scle cell proliferation and extracellular matrix accumulation. Halofug inone was used to block collagen production and smooth muscle cell pro liferation in cell cultures and in a rabbit model of an end to-end ana stomosis of the right common carotid artery. Animals were fed a nontox ic dose of halofuginone. Eighteen rabbits were fed the inhibitor in a randomized blinded fashion and were examined after 4 weeks by harvesti ng the arteries after perfusion fixation at physiologic pressures. Res ults: Halofuginone inhibited smooth muscle cell proliferation in vitro and had no effect on cell viability. Morphometric quantification veri fied that halofuginone treatment significantly attenuated anastomotic intimal thickness. Conclusion: Oral administration of halofuginone inh ibits intimal hyperplasia at vascular anastomoses. Intimal hyperplasia inhibition by halofuginone may be a therapeutic option for preventing arterial stenosis in vascular surgery.