Arterial Thrombin Activity After Angioplasty in an Atherosclerotic Rabbit Model

Background A 2-hour infusion of the direct thrombin inhibitor hirudin at the time of balloon angioplasty limits restenosis in the focally atherosclerotic rabbit. Although short-term administration of hirudin may have a prolonged biological effect, the effect of hirudin on vessel thrombin activity has not been previously studied in an animal model of angioplasty. We hypothesized that a short intravenous infusion of hirudin would result in prolonged inhibition of arterial wall–associated thrombin activity (ATA) after angioplasty. Methods and Results Sixty-one rabbits received recombinant hirudin (r-hirudin) (1 mg/kg bolus plus 1 mg · kg − 1 · h − 1 ×2 hours) or bolus heparin (controls, 150 U/kg) intravenously at the time of femoral balloon angioplasty. ATA was measured through exposure of arterial segments ex vivo to fibrinogen and conducting an assay for fibrinopeptide A (FPA). ATA was low in nonballooned, atherosclerotic vessels (FPA=0.5±0.3 ng · mL − 1 · mg − 1 ) but increased significantly at 24 hours after angioplasty in the heparin group (3.7±0.9 ng · mL − 1 · mg − 1 , P <.01 versus baseline, n=9) but not in the hirudin group (FPA=1.4±0.3; P =NS versus baseline, P <.02 versus heparin controls, n=8). The time course of ATA after angioplasty was assessed in 44 rabbits. Thrombin activity peaked at 48 hours and declined to baseline at 72 hours and 7 days. FPA values between the heparin and r-hirudin groups were similar at these later time points. Conclusions A 2-hour intravenous infusion of r-hirudin suppressed ATA measured 24 hours after angioplasty in the focally atherosclerotic rabbit. This prolonged biological effect may account, in part, for the reduction in restenosis seen in this model.