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.
Imanishi
T
T
Department of Medicine, Wakayama Medical College, Japan.
Arita
M
M
Hamada
M
M
Tomobuchi
Y
Y
Hano
T
T
Nishio
I
I
D015906:Angioplasty, Balloon, Coronary / Q000009:adverse effects* / Q000295:instrumentation; D000818:Animals; D000991:Antithrombins / Q000008:administration & dosage* / Q000494:pharmacology; D001120:Arginine / Q000031:analogs & derivatives; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology; D020212:Carotid Artery Injuries; D017536:Carotid Artery, Common / Q000187:drug effects* / Q000473:pathology; D016503:Drug Delivery Systems; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D006965:Hyperplasia; D010875:Pipecolic Acids / Q000008:administration & dosage* / Q000494:pharmacology; D011092:Polyethylene Glycols; D011817:Rabbits; D013449:Sulfonamides; D017539:Tunica Intima / Q000187:drug effects* / Q000293:injuries / Q000473:pathology
D000991:Antithrombins; D010875:Pipecolic Acids; D013449:Sulfonamides; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D011092:Polyethylene Glycols; D001120:Arginine; C031942:argatroban