Effects of locally administration of argatroban using a hydrogel-coated balloon catheter on intimal thickening induced by balloon injury

The purpose of this study was to evaluate the inhibitory effects of locally delivered argatroban, a competitive inhibitor of thrombin-induced platelet activation, on intimal proliferation after balloon injury. A hydrogel-coated balloon catheter was immersed 3 times in an argatroban/saline solution (1, 0.1, or 0.01 mg/ml) for 60 s and inflated at 6 atm pressure for 1 min in the rabbit common carotid artery. Immersion in a saline solution without drug followed by the same procedure served as a control. Accumulation of argatroban in the vascular wall was confirmed by chemical determination using high-performance liquid chromatography (HPLC). The concentration of argatroban in the vessel wall immediately after deflation after balloon immersion in solutions of 1 and 0.1 mg/ml was 14.8 +/- 10.9 and 5.5 +/- 4.6 nmol/g wet weight of artery, respectively. Argatroban was not detected in arteries treated with a balloon that had been immersed in the 0.01 mg/ml argatroban/saline solution. Intima-media area ratios 20 days after balloon injury in the groups treated with 1 mg/ml (n = 8) and 0.1 mg/ml (n = 6) agratoban were significantly smaller than that in the groups treated with 0.01 mg/ml (n = 7) argatroban or saline (n = 8) (0.35 +/- 0.11, 0.50 +/- 0.17, 1.24 +/- 0.39, and 1.35 +/- 0.43, respectively; p < 0.001). These data suggest that locally administered argatroban dose-dependently inhibits intimal thickening in a rabbit model of carotid artery injury.