Neointimal thickening after severe coronary artery injury is limited by a short-term administration of a factor Xa inhibitor. Results in a porcine model.
Neointimal thickening after severe coronary artery injury is limited by a short-term administration of a factor Xa inhibitor. Results in a porcine model.
复制标题
严重冠状动脉损伤后的新内膜增厚可通过短期施用 Xa 因子抑制剂来限制。
作者：
R. Schwartz;D. Holder;D. Holmes;J. Veinot;A. Camrud;M. Jorgenson;Robert G. Johnson
背景
富含纤维蛋白和血小板的血栓形成是经皮腔内冠状动脉成形术后的初始事件。因此，我们测试了这样的假设：在猪冠状动脉球囊血管成形术模型中，短期施用重组蜱抗凝肽（rTAP）（一种 Xa 因子抑制剂）会减少损伤后 28 天的新内膜厚度。
方法和结果
向研究猪连续静脉输注 rTAP（平均剂量，194 微克.kg-1.min-1）或安慰剂（仅载体）60 小时。抗凝的目标是将活化凝血时间维持在200秒。手术前 2 天插入中心静脉导管。在冠状动脉损伤当天，给动物注射rTAP（6.5毫克），然后通过标准方法在右冠状动脉、回旋支或左冠状动脉前降支中用超大金属线圈进行损伤。安乐死 28 天后，rTAP 和载体对照之间的血管损伤没有观察到显着差异。与对照组相比（0.48 +/- 0.12 mm，P < .001），rTAP 治疗动物的新内膜增厚明显减少（厚度，平均值+/-SD：0.30 +/-0.08 mm）。
结论
在猪模型中冠状动脉损伤后短时间内给予特定因子 Xa 抑制剂 rTAP 时，可导致新生内膜厚度长期减少。这些结果暗示了新内膜形成中的凝血酶生成，并表明在手术后立即施用强效抗血栓药几天可能会影响冠状动脉损伤的长期结果，从而减少新内膜形成。
BACKGROUND
Fibrin- and platelet-rich thrombus formations occur as the initial event after percutaneous transluminal coronary angioplasty. We therefore tested the hypothesis that short-term administration of the recombinant tick anticoagulant peptide (rTAP), a factor Xa inhibitor, would reduce the thickness of neointima at 28 days after injury in a porcine coronary balloon angioplasty model.
METHODS AND RESULTS
Continuous intravenous infusion of rTAP (average dose, 194 micrograms . kg-1 . min-1) or placebo (vehicle only) was given to the study pigs for 60 hours. The goal of anticoagulation was to maintain the activated clotting time at 200 seconds. A central venous catheter was inserted 2 days before the procedure. On the day of coronary injury, the animals were administered boluses of rTAP (6.5 mg) and then underwent injury with an oversized metallic coil by standard methods in the right, circumflex, or left anterior descending coronary artery. No significant difference in vascular injury between rTAP and vehicle control was observed after euthanasia at 28 days. Significantly less neointimal thickening occurred in the rTAP-treated animals (thickness, mean +/-SD: 0.30 +/-0.08 mm) compared with the control (0.48 +/- 0.12 mm, P< .001).
CONCLUSIONS
The specific factor Xa inhibitor rTAP, when given in fully anticoagulant doses for a short duration after coronary artery injury in the porcine model, resulted in a long-term decrease in neointimal thickness. These results implicate thrombin generation in neointimal formation and suggest that administration of a potent antithrombotic for several days immediately after the procedure may influence the long-term outcome of the coronary injury with a decrease in neointimal formation.