Barry W L, Gimple L W, Humphries J E, Powers E R, McCoy K W, Sanders J M, Owens G K, Sarembock I J
Cardiovascular Division, Department of Medicine, University of Virginia Health Sciences Center, Charlottesville 22908, USA.
Circulation. 1996 Jul 1;94(1):88-93. doi: 10.1161/01.cir.94.1.88.
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.
Sixty-one rabbits received recombinant hirudin (r-hirudin)(1 mg/kg bolus plus 1 mg x kg(-1) x h(-1)x2hours) 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 x mL(-1) x mg(-1)) but increased significantly at 24 hours after angioplasty in the heparin group (3.7+/-0.9 ng x mL(-1) x 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.
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.
在球囊血管成形术时静脉输注直接凝血酶抑制剂水蛭素2小时可限制局部动脉粥样硬化兔的再狭窄。尽管水蛭素的短期给药可能具有延长的生物学效应，但此前尚未在血管成形术动物模型中研究水蛭素对血管凝血酶活性的影响。我们推测，水蛭素的短期静脉输注会导致血管成形术后动脉壁相关凝血酶活性（ATA）受到长期抑制。
61只兔子在股动脉球囊血管成形术时静脉注射重组水蛭素（r - 水蛭素）（1 mg/kg推注加1 mg·kg⁻¹·h⁻¹×2小时）或推注肝素（对照组，150 U/kg）。通过将离体动脉段暴露于纤维蛋白原并进行纤维蛋白肽A（FPA）测定来测量ATA。在未进行球囊扩张的动脉粥样硬化血管中ATA较低（FPA = 0.5±0.3 ng·mL⁻¹·mg⁻¹），但在血管成形术后24小时，肝素组显著升高（3.7±0.9 ng·mL⁻¹·mg⁻¹，与基线相比P<0.01，n = 9），而水蛭素组未升高（FPA = 1.4±0.3；与基线相比P = 无显著性差异，与肝素对照组相比P<0.02，n = 8）。在44只兔子中评估了血管成形术后ATA的时间进程。凝血酶活性在48小时达到峰值，并在72小时和7天时降至基线。在这些较晚时间点，肝素组和r - 水蛭素组的FPA值相似。
在局部动脉粥样硬化兔中，静脉输注r - 水蛭素2小时可抑制血管成形术后24小时测量的ATA。这种延长的生物学效应可能部分解释了该模型中观察到的再狭窄减少。
