Late effects of locally delivered mitomycin C on formation of neointima and on vasomotor response to acetylcholine

Background: Balloon angioplasty damages endothelial cells and stimulates smooth muscle cell proliferation. The effects of local cytotoxic drug therapy on formation of neointima and late endothelial function are not known. This study was designed to determine whether direct infusion of mitomycin C via a microporous balloon catheter could significantly reduce formation of neointima after angioplasty. Furthermore, we investigated whether endothelial cell function is normal 7 weeks after the initial microporous angioplasty procedure. Methods: In 34 New Zealand white rabbits, bilateral external iliac arteries underwent balloon angioplasty, followed by either high-dose (0.66 mg/kg) or low-dose (0.025 mg/kg) mitomycin C in one iliac artery and saline infusion in the contralateral artery, and a control group was given saline in both vessels. Formation of neointima was measured in the iliac arteries after 7 weeks by morphometry. Before sacrifice of 17 'angioplasty' rabbits and three undamaged rabbits, graded doses of acetylcholine and isosorbide dinitrate were infused in the distal aorta, and the iliac artery diameter was measured by computerized quantitative angiography. Results: No significant differences in the absolute area of the intima or the intima: media ratio were demonstrated between control arteries and arteries that were directly infused with either high-dose or low-dose mitomycin. However, within the high-dose group, the mitomycin-treated vessel had a significantly lesser extent of formation of intimal hyperplasia (0.17±0.03 versus 0.27±0.03 mm², P<0.03) and lower intima:media area ratio (0.60±0.31 versus 1.09±0.42, P<0.03) than the contralateral saline-treated vessel. Significant increases in mean luminal iliac artery diameter [0.18 mm (10.5%) at 1 min and 0.23 mm (13%) at 3 min, P<0.05)] from baseline values following acetylcholine were observed in previously damaged iliac arteries. This vasodilatory response was not different from that in undamaged arteries. Conclusions: Local delivery of mitomycin C had no favorable effect on the inhibition of intimal hyperplasia compared with control saline-treated arteries. Normal endothelial function, determined on the basis of dilatory response to acetylcholine, can be demonstrated 7 weeks after balloon angioplasty injury.