Rubin B G, Toursarkissian B, Petrinec D, Yang L Y, Eisenberg P R, Abendschein D R
Department of Surgery, Washington University, St Louis, MO 63110, USA.
J Vasc Surg. 1996 Nov;24(5):865-70. doi: 10.1016/s0741-5214(96)70024-1.
We have previously shown that preincubation of whole blood clots with recombinants tissue factor pathway inhibitor (rTFPI) attenuates clot-associated procoagulant activity assessed ex vivo. This study was undertaken to determine whether a single local application of rTFPI induces similar attenuation of the procoagulant activity on preclotted Dacron grafts implanted in an artery in vivo.
Dacron grafts (4 mm x 4 cm long) were preclotted in porcine blood and incubated with either rTFPI (5 mg/ml) or arginine-phosphate buffer for 15 minutes. Grafts were implanted end-to-end in the femoral arteries of 10 pigs, with one rTFPI-treated and one buffer-treated graft implanted in each animal. Animals did not undergo anticoagulation either before or after graft implantation. Radiolabeled porcine fibrinogen was injected intravenously, and the grafts underwent perfusion for 1 hour. A subgroup of animals (n = 7) also had infusion of radiolabeled autologous platelets at the time of administration of radiolabeled fibrinogen.
Fibrin(ogen) deposition was decreased in rTFPI-treated grafts by 36% +/- 7% (mean +/- SEM) compared with buffer-treated grafts (p = 0.001). Platelet deposition was also reduced in the rTFPI-treated grafts by 31% +/- 15%, although the reduction did not reach statistical significance (p = 0.10). The extent of rTFPI-mediated attenuation of fibrin(ogen) versus platelet deposition varied independently among animals.
Clot-directed anticoagulant effects of rTFPI appear to be useful for substantially decreasing the thrombogenicity of Dacron grafts immediately after their implantation. Chronic studies to determine whether the decreases in thrombogenicity result in improved long-term graft patency appear warranted.
我们之前已经表明，用重组组织因子途径抑制剂（rTFPI）对全血凝块进行预孵育可减弱体外评估的与凝块相关的促凝血活性。本研究旨在确定单次局部应用rTFPI是否能在体内动脉植入的预凝涤纶移植物上诱导类似的促凝血活性减弱。
将涤纶移植物（4毫米×4厘米长）在猪血中预凝，并用rTFPI（5毫克/毫升）或精氨酸 - 磷酸盐缓冲液孵育15分钟。将移植物端端植入10头猪的股动脉中，每只动物植入一个经rTFPI处理的移植物和一个经缓冲液处理的移植物。在移植物植入前后，动物均未接受抗凝治疗。静脉注射放射性标记的猪纤维蛋白原，移植物灌注1小时。一组亚组动物（n = 7）在注射放射性标记的纤维蛋白原时还输注了放射性标记的自体血小板。
与经缓冲液处理的移植物相比，经rTFPI处理的移植物中纤维蛋白（原）沉积减少了36%±7%（平均值±标准误）（p = 0.001）。经rTFPI处理的移植物中血小板沉积也减少了31%±15%，尽管这种减少未达到统计学意义（p = 0.10）。rTFPI介导的纤维蛋白（原）与血小板沉积减弱的程度在动物之间独立变化。
rTFPI的凝块导向抗凝作用似乎有助于在涤纶移植物植入后立即大幅降低其血栓形成性。进行长期研究以确定血栓形成性的降低是否会导致移植物长期通畅性改善似乎是有必要的。
