Colchicine Reduces Intimal Hyperplasia in a Canine Model of Balloon Angioplasty

Aim: Restenosis due to intimal hyperplasia following percutaneous transluminal angioplasty limits its long term efficacy. We evaluated the effect of colchicine on the development of intimal hyperplasia following balloon angioplasty. Material and Methods: Adult Mongrel dogs underwent balloon angioplasty of the right iliofemoral artery. Group 1 served as control, while groups 2 and 3 received 100 and 500 μg/kg/d, respectively of colchicine by gavage starting two days before angioplasty and continued for 14 days. Before angioplasty and at day 14 before sacrifice, blood samples were collected for drug toxicity analysis and the determination of plasma vascular endothelial growth factor (VEGF) levels. Animals were euthanized and iliofemoral arteries were perfusion fixed in situ and processed for histological and morphometric analysis. Results: Balloon angioplasty without colchicine resulted in 309% increase in intima/media ratio (p 0.001) compared with healthy arteries. Low-dose colchicine resulted in 15% (p=0.6 vs. control), while high-dose colchicine resulted in 74% (p 0.001 vs. control) reduction in intimal thickness. Low-dose and high-dose colchicine resulted in 42.3% and 68.4% reduction in intima/media ratio, respectively (both p 0.001). The intima/media ratio was not different between high-colchicine group and healthy uninjured group (p=03). VEGF plasma levels in the low-dose colchicine group were 107% (p=0.004) higher than those of the control group and 75% (p=0.02) higher than those of the high-dose colchicine group. No significant difference was found between VEGF concentrations of the control and high-dose colchicine groups (p=0.8). Serum creatinine, alanine transaminase (ALT) levels and red blood cell and platelet counts were within normal range at sacrifice in all groups. After angioplasty, white blood cell counts in the control group were significantly higher (p 0.05) than the upper limit of normal, but were lower in both colchicine groups, however, they were not different from lower limit of normal (p=0.8). Conclusion: Orally administered colchicine in a dose of 500 μg/kg/day for two weeks was successful in reducing intimal hyperplasia following balloon injury of the canine iliofemoral arteries and without apparent systemic toxicity.