Halofuginone, a specific collagen type I inhibitor, reduces anastomotic intimal hyperplasia
E. T. Choi, A. D. Callow, N. L. Sehgal, D. M. Brown and U. S. Ryan
Department of Surgery, Washington University School of Medicine, St. Louis, Mo.
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.
