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 loc ally administered argatroban, a competitive inhibitor of thrombin-indu ced platelet activation, on restenosis after balloon angioplasty. 2. A hydrogel-coated balloon catheter was immersed three times in argatrob an/saline solution (1 mg/mL) for 60 s, inflated to a pressure of 606 k Pa and left in the rabbit common carotid artery for 1 min, The same pr ocedure was performed, without drug, as a control, The pharmacokinetic s of delivered argatroban in the arterial wall were assessed using [C- 14]-argatroban. Platelet deposition 2 h after balloon injury was quant ified by fluorescence studies using antiplatelet antibody, Vascular sm ooth muscle cell (VSMC) proliferation 3 days after balloon injury was assessed by immunohistochemical staining for proliferative cell nuclea r 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 we re 24.63, 0.49 and 0.11 nmol/g wet weight of artery, respectively, Arg atroban was undetected 24 h after deflation, Two hours after deflation , argatroban-treated arteries showed less platelet adhesion than salin e-treated controls, The mean number of PCNA-positive cells was 16.9 an d 43.8% in the argatroban and control groups, respectively (P<0.01), I n 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 r estenosis 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 an d that locally administered argatroban using hydrogel-coated balloon c atheter may prevent post-percutaneous transluminal coronary angioplast y restenosis.