Effects of locally administered argatroban on restenosis after balloon angioplasty: experimental and clinical study.
1. This study was undertaken to evaluate the preventive effects of locally administered argatroban, a competitive inhibitor of thrombin-induced platelet activation, on restenosis after balloon angioplasty. 2. A hydrogel-coated balloon catheter was immersed three times in argatroban/saline solution (1 mg/mL) for 60 s, inflated to a pressure of 606 kPa and left in the rabbit common carotid artery for 1 min. The same procedure was performed, without drug, as a control. The pharmacokinetics of delivered argatroban in the arterial wall were assessed using [14C]-argatroban. Platelet deposition 2 h after balloon injury was quantified by fluorescence studies using antiplatelet antibody. Vascular smooth muscle cell (VSMC) proliferation 3 days after balloon injury was assessed by immunohistochemical staining for proliferative cell nuclear antigen (PCNA). In a clinical study, we divided 50 elective patients into two groups: argatroban and control. 3. In the experimental study, the mean quantities of argatroban at 0, 2 and 6 h after deflation were 24.63, 0.49 and 0.11 nmol/g wet weight of artery, respectively. Argatroban was undetected 24 h after deflation. Two hours after deflation, argatroban-treated arteries showed less platelet adhesion than saline-treated controls. The mean number of PCNA-positive cells was 16.9 and 43.8% in the argatroban and control groups, respectively (P < 0.01). In the clinical study, the mean late gain loss was 8.2 and 27.3% in the argatroban and control groups, respectively (P < 0.05). The mean late restenosis rate was 11.1 and 41.4% in the argatroban and control groups, respectively (P < 0.05). 4. These data suggest that blood coagulation plays a significant role in VSMC proliferation after balloon injury and that locally administered argatroban using hydrogel-coated balloon catheter may prevent post-percutaneous transluminal coronary angioplasty restenosis.
Imanishi
T
T
Department of Medicine, Wakayama Medical College, Japan.
Arita
M
M
Tomobuchi
Y
Y
Hamada
M
M
Hano
T
T
Nishio
I
I
D000800:Angioplasty, Balloon; D000818:Animals; D000991:Antithrombins / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D001120:Arginine / Q000031:analogs & derivatives; D002455:Cell Division / Q000187:drug effects; D003327:Coronary Disease / Q000517:prevention & control*; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects; D010875:Pipecolic Acids / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D015539:Platelet Activation / Q000187:drug effects; D011817:Rabbits; D013449:Sulfonamides
D000991:Antithrombins; D010875:Pipecolic Acids; D013449:Sulfonamides; D001120:Arginine; C031942:argatroban