Fibrin-rich and platelet-rich thrombus formation on neointima: Recombinant tissue factor pathway inhibitor prevents fibrin formation and neointimal development following repeated balloon injury of rabbit aorta
Fibrin-rich and platelet-rich thrombus formation on neointima: Recombinant tissue factor pathway inhibitor prevents fibrin formation and neointimal development following repeated balloon injury of rabbit aorta
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DOI：
10.1055/s-0037-1615237
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发表时间：
1998-09-01
影响因子：
6.7
通讯作者：
Sumiyoshi, A
中科院分区：
文献类型：
--
作者：
Asada, Y;Hara, S;Sumiyoshi, A
血栓形成和新生内膜生长是球囊血管成形术后再狭窄的关键事件。然而，病变血管对球囊血管成形术引起的损伤的反应尚未得到很好的研究。我们研究了血栓形成和新生内膜的发展后，球囊损伤到先前诱导的新生内膜在兔主动脉和重组组织因子途径抑制剂（rTFPI）对这些反应的影响。使用Fogarty 4F球囊导管在1.75个大气压下对兔胸主动脉进行损伤（第一次损伤），4周后，在1.4臂处用Swan-Ganz 5 F球囊导管对相同的血管进行第二次损伤。（轻度损伤组）或1.8 atm（严重损伤组），并且在此之后立即通过Swan-Ganz导管的中心管将rTFPI（100 μ g/kg体重）或生理盐水逆行推注到损伤节段中。第二次损伤后20 min，轻度损伤组的损伤表面覆盖有富含血小板的血栓，重度损伤组的损伤表面覆盖有富含纤维蛋白的血栓。在富含纤维蛋白的血栓下方观察到组织因子（TF）化学染色阳性的受损内膜平滑肌细胞。二次损伤后4周，重度损伤组新生内膜厚度明显大于轻度损伤组。二次损伤后4周，rTFPI的推注显著抑制了损伤表面的纤维蛋白形成，并显著减少了重度损伤组中的新生内膜的形成。这些结果表明，TF依赖性凝血途径是主要负责富含纤维蛋白的血栓形成，并可能发挥重要作用，在新生内膜的发展后，球囊损伤兔主动脉新生内膜。此外，对损伤血管推注rTFPI可防止球囊血管成形术后附壁血栓形成和新生内膜生长。
Thrombus formation and neointimal growth are the critical events in restenosis after balloon angioplasty. However, the responses of diseased vessels to injuries caused by balloon angioplasty have not been well examined. We investigated the thrombus formation and neointimal development following the balloon injury to the previously induced neointima in the rabbit aorta and the effects of recombinant tissue factor pathway inhibitor (rTFPI) on these responses. Rabbit thoracic aortas were subjected to injury with a Fogarty 4F balloon catheter at 1.75 atm (first injury), and 4 weeks later the same vessels were subjected iu the second injury with a Swan-Ganz 5F balloon catheter at 1.4 arm (mild-injury group) or 1.8 atm (severe-injury group), and immediately after that a retrograde bolus injection of rTFPI (100 mu g/kg body weight) or saline was performed into the injured segments via the central tube of the Swan-Ganz catheter. Twenty minutes after the second injury, the injured surfaces were covered with platelet-rich thrombi in the mild-injury group and with fibrin-rich thrombi in the severe-injury group. Damaged intimal smooth muscle cells, which were immunohistochemically positive for tissue factor (TF), were observed beneath the fibrin rich thrombi. The neointima 4 weeks after the second injury was significantly thicker in the severe-injury group than in the mild-injury group. The bolus infusion of rTFPI markedly inhibited fibrin formation on the injured surfaces, and significantly reduced the neointimal development in the severe-injury group at 4 weeks after the second injury. These results indicate that TF-dependent coagulation pathway is primarily responsible for fibrin-rich thrombus formation and may play an important role in neointimal development following the balloon injury to the rabbit aortic neointima. Additionally the bolus administration of rTFPI to the injured vessels could prevent mural thrombus formation and neointimal growth after balloon angioplasty.