水蛭素与阿司匹林联合应用对大鼠颈动脉内膜切除术模型中血小板沉积的抑制作用。

Inhibition of platelet deposition by combined hirulog and aspirin in a rat carotid endarterectomy model.

作者信息

Hamelink J K, Tang D B, Barr C F, Jackson M R, Reid T J, Gomez E R, Alving B M

机构信息

Department of Hematology and Vascular Biology, Walter Reed Army Institute of Research, Washington, D.C.

出版信息

J Vasc Surg. 1995 Mar;21(3):492-8. doi: 10.1016/s0741-5214(95)70292-x.

DOI:10.1016/s0741-5214(95)70292-x

PMID:7877232

Abstract

PURPOSE

Hirulog, a thrombin-specific inhibitor, has shown efficacy in reducing arterial thrombosis in patients treated with aspirin who require angioplasty or have unstable angina. In this study, the effect of hirulog on reducing deposition of indium 111-labeled platelets was assessed in a surgical model of aspirin-treated rats undergoing carotid endarterectomy.

METHODS

Animals were randomly assigned to one of five groups: control (no aspirin or hirulog); aspirin alone (10 mg/kg); aspirin plus low-dose hirulog (0.2 mg/kg bolus followed by 0.5 mg/kg/hr); aspirin plus medium-dose hirulog (0.4 mg/kg bolus followed by 1.0 mg/kg/hr); or aspirin plus high-dose hirulog (0.6 mg/kg bolus followed by 1.5 mg/kg/hr). Hirulog was infused before surgery and continued until termination of the experiment 30 minutes after endarterectomy.

RESULTS

Platelet deposition in rats receiving aspirin alone was reduced by 19% +/- 23% SE (p = 0.26) compared with controls. Deposition in aspirin-treated groups receiving low-, medium-, and high-dose hirulog decreased in a dose-dependent manner by 37% +/- 20% (p = 0.048), 44% +/- 19% (p = 0.061), and 56% +/- 13% (p = 0.022), respectively. As the dose of hirulog was increased, the plasma hirulog levels and activated partial thromboplastin time ratios (final:initial) also increased in a dose-dependent manner. The mean plasma hirulog levels ranged from 0.74 +/- 0.08 micrograms/ml in the low-dose hirulog group to 2.55 +/- 0.08 micrograms/ml in the high-dose hirulog group, and the corresponding activated partial thromboplastin time ratios were 1.5 +/- 0.12 (p = 0.001) and 3.3 +/- 0.63 (p = 0.001). Bleeding was easily controlled by local hemostatic measures for all experimental groups.

CONCLUSION

Hirulog causes significant decrease in 111In-labeled platelet deposition in aspirin-treated rats subjected to microsurgical endarterectomy at doses that allow surgical hemostasis to be easily established.

摘要

目的

水蛭素是一种凝血酶特异性抑制剂，已显示出对需要血管成形术或患有不稳定型心绞痛且接受阿司匹林治疗的患者有减少动脉血栓形成的功效。在本研究中，在接受颈动脉内膜切除术的阿司匹林治疗大鼠的手术模型中，评估了水蛭素对减少铟111标记血小板沉积的作用。

方法

将动物随机分为五组之一：对照组（未用阿司匹林或水蛭素）；单独使用阿司匹林组（10mg/kg）；阿司匹林加低剂量水蛭素组（0.2mg/kg推注，随后0.5mg/kg/小时）；阿司匹林加中剂量水蛭素组（0.4mg/kg推注，随后1.0mg/kg/小时）；或阿司匹林加高剂量水蛭素组（0.6mg/kg推注，随后1.5mg/kg/小时）。在手术前输注水蛭素，并持续至内膜切除术后30分钟实验结束。

结果

与对照组相比，单独接受阿司匹林治疗的大鼠血小板沉积减少了19%±23%标准误（p=0.26）。接受低、中、高剂量水蛭素的阿司匹林治疗组的沉积量呈剂量依赖性下降，分别为37%±20%（p=0.048）、44%±19%（p=0.061）和56%±13%（p=0.022）。随着水蛭素剂量的增加，血浆水蛭素水平和活化部分凝血活酶时间比值（最终值：初始值）也呈剂量依赖性增加。低剂量水蛭素组的平均血浆水蛭素水平范围为0.74±0.08微克/毫升，高剂量水蛭素组为2.55±0.08微克/毫升，相应的活化部分凝血活酶时间比值分别为1.5±0.12（p=0.001）和3.3±0.63（p=0.001）。所有实验组的出血均可通过局部止血措施轻松控制。