Inhibition of intimal hyperplasia by local perivascular application of rapamycin and imatinib mesilate after carotid balloon injury.

Abstract

Purpose: Inhibition of the intimal hyperplasia after vascular surgery is an important issue. The purpose of this study is to define whether perivascular application of rapamycin, imatinib mesylate or cysteamine can reduce intimal hyperplasia in a carotid balloon injury model.

Methods: Each drug was mixed with 40% pluronic gel solution and was topically applied over the injured carotid artery evenly. Two or four weeks after injury, the arteries were harvested and morphometric analysis was done.

Results: The medial areas were not significantly different in each group and a thinning of the media as a toxic drug effect was not observed in any treatment group. The intimal area and intima-to-media (I/M) ratio were significantly reduced in rapamycin-treated group and imatinib-treated group (P < 0.05). But cysteamine-treated group showed a trend of decrease in I/M ratio in 2 weeks, but no difference in 4 weeks.

Conclusion: Perivascular delivery of imatinib or rapamycin with pluronic gel attenuated the development of intimal hyperplasia. But cysteamine did not. Further studies are needed to refine the optimal drug dosages in large animal models.