Inhibition of tissue factor-mediated coagulation markedly attenuates stenosis after balloon-induced arterial injury in minipigs.
Inhibition of tissue factor-mediated coagulation markedly attenuates stenosis after balloon-induced arterial injury in minipigs.
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DOI：
10.1161/01.cir.96.2.646
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发表时间：
1997-07
期刊：
影响因子：
37.8
通讯作者：
L. Oltrona;C. M. Speidel;D. Recchia;S. Wickline;P. Eisenberg;D. Abendschein
中科院分区：
文献类型：
--
作者：
L. Oltrona;C. M. Speidel;D. Recchia;S. Wickline;P. Eisenberg;D. Abendschein
球囊损伤动脉壁中组织因子的暴露和上调可能导致凝血激活延长，从而导致再狭窄。本研究旨在确定使用组织因子途径抑制剂（TFPI）短暂或更长时间抑制组织因子介导的凝血是否会减轻球囊诱导动脉损伤后的新生内膜形成和管腔狭窄。方法和结果：反复球囊过度充气损伤了喂食致动脉粥样硬化饮食的小型猪的颈动脉，这是一种快速产生复杂的斑块样新生内膜病变和高度管腔狭窄的过程。在球囊损伤前15分钟开始静脉内给予重组TFPI（rTFPI），高剂量（0.5 mg/kg推注和100 μ g x kg（-1）x min（-1））持续3小时（n=7）或24小时（n=6），或低剂量（0.5 mg/kg和25 μ g x kg（-1）x min（-1））持续24小时（n=6）。对照动物接受静脉内肝素（100 U x kg（-1）x h（-1））3小时（n=6）或24小时（n=7）或阿司匹林（5 mg/kg P.O.）然后肝素24小时（n=7）。损伤后4周组织学评估的管腔狭窄在接受rTFPI或肝素3小时的动物中分别为73+/-17%和76+/-18%（平均值+/-SEM）。相比之下，给予高剂量和低剂量rTFPI 24小时的猪的管腔狭窄分别为11+/-12%和6+/-3%，而给予肝素24小时的猪的管腔狭窄为46+/-22%，给予肝素和阿司匹林的猪的管腔狭窄为40+/-19%（P<.0002）。结论：在深动脉损伤后的前24小时内抑制组织因子介导的凝血似乎对减轻随后的新生内膜形成和狭窄特别有效。
BACKGROUND Exposure and upregulation of tissue factor in the wall of balloon-injured arteries may result in prolonged activation of coagulation contributing to restenosis. This study was designed to determine whether brief or more prolonged inhibition of tissue factor-mediated coagulation with tissue factor pathway inhibitor (TFPI) attenuates neointimal formation and luminal stenosis after balloon-induced arterial injury. METHODS AND RESULTS The carotid artery of minipigs fed an atherogenic diet was injured by repetitive balloon hyperinflations, a procedure that rapidly yields complex, plaque-like neointimal lesions and high-grade luminal stenosis. Recombinant TFPI (rTFPI) was administered intravenously beginning 15 minutes before balloon injury as either a high dose (0.5 mg/kg bolus and 100 microg x kg(-1) x min(-1)) for 3 hours (n=7) or 24 hours (n=6) or as a low dose (0.5 mg/kg and 25 microg x kg(-1) x min(-1)) for 24 hours (n=6). Control animals received intravenous heparin (100 U x kg(-1) x h(-1)) for 3 hours (n=6) or 24 hours (n=7) or aspirin (5 mg/kg P.O.) followed by heparin for 24 hours (n=7). Luminal stenosis, assessed histologically 4 weeks after injury, was 73+/-17% and 76+/-18% (mean+/-SEM) in animals that received rTFPI or heparin for 3 hours, respectively. In contrast, luminal stenosis was only 11+/-12% and 6+/-3% in pigs given high and low doses, respectively, of rTFPI for 24 hours compared with 46+/-22% in pigs given heparin for 24 hours and 40+/-19% in those given both heparin and aspirin (P<.0002). CONCLUSIONS Inhibition of tissue factor-mediated coagulation during the first 24 hours after deep arterial injury appears to be particularly effective for attenuating subsequent neointimal formation and stenosis.