局部应用组织型纤溶酶原激活剂对静脉纤溶活性的影响：体外和体内研究

Effect of locally applied tissue-type plasminogen activator on venous fibrinolytic activity: in vitro and in vivo investigations.

作者信息

Underwood M J, More R S, Gershlick A H, de Bono D P

机构信息

Academic Department of Cardiology, Glenfield General Hospital, Leicester, United Kingdom.

出版信息

Cardiovasc Res. 1993 Dec;27(12):2270-3. doi: 10.1093/cvr/27.12.2270.

DOI:10.1093/cvr/27.12.2270

PMID:8313438

Abstract

OBJECTIVES

The aim was to see if topically applied tissue-type plasminogen activator (tPA) would enhance the fibrinolytic activity of saphenous vein prepared before coronary artery surgery, persist in the vessel wall after perfusion, and reduce thrombus formation after vascular injury.

METHODS

Varying doses of tPA were applied to the intimal surface of the saphenous vein obtained from patients before coronary artery surgery. After flushing, biopsies were incubated on fibrin plates and areas of lysis quantified. Samples treated with tPA (1 mg.ml-1) were perfused in vitro for 30 minutes. Fibrinolytic activity was assessed on fibrin plates and tPA activity (in tissue extract) measured with chromogenic assays. The effect of locally applied tPA on thrombus formation was quantified with a rat vena cava model based on vascular injury and stasis.

RESULTS

Local application of 1 mg.ml-1 tPA enhanced fibrinolysis under static conditions [median (interquartile range) of diameter of lysis.mm-1 (n = 8 both groups), treated vein 16.5 (14.1-17.9), control 8.5 (5.75-10.37) (p < 0.05)]. This enhanced activity was retained after in vitro perfusion [median (interquartile range) of areas of lysis.mm-2 (n = 8 all groups), treated vein 170.8 (132.8-205.1), control (unperfused) 69.5 (45.2-87.6), perfused (untreated) 76.7 (58.3-98.9) (p < 0.01)]. Specific tPA activity in these samples was also increased (p < 0.05). Local application of tPA (1 mg.ml-1) to damaged rat vena cava reduced subsequent thrombus formation [median thrombus weight.mg-1 (interquartile range) (n = 8), tPA treated 2.5 (0.25-5.75), control 38.5 (32-43) (p < 0.001)].

CONCLUSIONS

Locally applied tPA enhances the fibrinolytic activity of damaged vessel wall, persists after perfusion, and reduces thrombus formation after vascular injury. This method of treating conduits before their use as vascular grafts merits further study to see if it is effective in reducing early graft thrombosis while maintaining systemic haemostasis.

摘要

目的

旨在观察局部应用组织型纤溶酶原激活剂（tPA）是否会增强冠状动脉手术前制备的大隐静脉的纤溶活性，在灌注后是否会持续存在于血管壁中，以及是否会减少血管损伤后的血栓形成。

方法

将不同剂量的tPA应用于冠状动脉手术前从患者获取的大隐静脉内膜表面。冲洗后，将活检组织在纤维蛋白平板上孵育，并对溶解区域进行定量。用1mg/ml的tPA处理的样本在体外灌注30分钟。在纤维蛋白平板上评估纤溶活性，并用显色测定法测量（组织提取物中的）tPA活性。基于血管损伤和血流淤滞，用大鼠腔静脉模型对局部应用tPA对血栓形成的影响进行定量。

结果

局部应用1mg/ml的tPA在静态条件下增强了纤溶作用[溶解直径的中位数（四分位间距）.mm-1（两组均n = 8），处理组静脉为16.5（14.1 - 17.9），对照组为8.5（5.75 - 10.37）（p < 0.05）]。这种增强的活性在体外灌注后得以保留[溶解面积的中位数（四分位间距）.mm-2（所有组均n = 8），处理组静脉为170.8（132.8 - 205.1），对照组（未灌注）为69.5（45.2 - 87.6），灌注组（未处理）为76.7（58.3 - 98.9）（p < 0.01）]。这些样本中的特异性tPA活性也有所增加（p < 0.05）。将1mg/ml的tPA局部应用于受损的大鼠腔静脉可减少随后的血栓形成[血栓重量的中位数.mg-1（四分位间距）（n = 8），tPA处理组为2.5（0.25 - 5.75），对照组为38.5（32 - 43）（p < 0.001）]。