局部应用重组纤溶酶可在猪动静脉移植血栓形成模型中实现有效的溶栓。

Locally applied recombinant plasmin results in effective thrombolysis in a porcine model of arteriovenous graft thrombosis.

作者信息

Hoefer Imo E, Stroes Erik S G, Pasterkamp Gerard, Levi Marcel M, Reekers Jim A, Verhagen Hence J M, Meijers Joost C, Humphries John E, Rotmans Joris I

机构信息

Laboratory of Experimental Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands.

出版信息

J Vasc Interv Radiol. 2009 Jul;20(7):951-8. doi: 10.1016/j.jvir.2009.03.043. Epub 2009 May 28.

DOI:10.1016/j.jvir.2009.03.043

PMID:19481472

Abstract

PURPOSE

Arteriovenous (AV) graft thrombosis is a frequent complication in patients undergoing hemodialysis. Thrombolytic therapy with tissue plasminogen activator (TPA) is hampered by the risk of bleeding complications. Locally delivered plasmin may have similar thrombolytic efficacy with a superior safety profile, so herein it was compared with TPA in a porcine model of AV graft thrombosis.

MATERIALS AND METHODS

AV grafts were created bilaterally between the carotid artery and jugular vein. Graft thrombosis was induced by clamping the grafts for 1 hour. On day 3, one graft was treated with a 2-mL local recombinant plasmin injection (10 mg; n = 10) with the contralateral graft being infused with TPA (10 mg, n = 8) or saline solution (n = 2). Thrombolytic efficacy was assessed by weighing the residual clot and released clot fragments.

RESULTS

After saline solution injection, the mean residual clot weight in the graft was 618 mg. Local administration of TPA showed the least residual clot in the graft (69 mg +/- 26), with large clot particles reaching the venous outflow (241 mg +/- 23). Plasmin treatment significantly reduced the released clot mass versus TPA (52 mg +/- 23; P < .05), whereas residual clot weight was greater compared with TPA treatment (140 mg +/- 22; P < .05). Overall thrombolytic activity of plasmin (ie, residual clot plus released clot) was significantly better than that of TPA (193 mg +/- 25 vs 310 mg +/- 35; P < .05).

CONCLUSIONS

The thrombolytic efficacy of recombinant plasmin was shown to be superior to that of TPA in this study.

摘要

目的

动静脉（AV）移植物血栓形成是接受血液透析患者的常见并发症。组织型纤溶酶原激活剂（TPA）溶栓治疗存在出血并发症风险。局部给予纤溶酶可能具有相似的溶栓效果且安全性更高，因此在本研究中，在猪AV移植物血栓形成模型中将其与TPA进行比较。

材料与方法

在双侧颈动脉和颈静脉之间建立AV移植物。通过夹闭移植物1小时诱导血栓形成。在第3天，一个移植物用2 mL局部重组纤溶酶注射治疗（10 mg；n = 10），对侧移植物注入TPA（10 mg，n = 8）或生理盐水（n = 2）。通过称量残余血栓和释放的血栓碎片评估溶栓效果。

结果

注射生理盐水后，移植物中平均残余血栓重量为618 mg。局部给予TPA显示移植物中残余血栓最少（69 mg±26），大量血栓颗粒进入静脉流出道（241 mg±23）。与TPA相比，纤溶酶治疗显著减少了释放的血栓量（52 mg±23；P < 0.05），而残余血栓重量比TPA治疗时更大（140 mg±22；P < 0.05）。纤溶酶的总体溶栓活性（即残余血栓加释放的血栓）显著优于TPA（193 mg±25 vs 310 mg±35；P < 0.05）。