ENDARTERECTOMY: PREVENTION OF THROMBOSIS & RESTENOSIS

在不增加出血的情况下增强溶栓反应 风险，重组赖氨酸-纤溶酶原的抗血栓作用 纤溶酶原中间体(r-LysPgn)已被 在狒狒血栓形成和溶解模型中进行了检查。这个 R-LysPgn单独或联合应用的量效关系 组织纤溶酶原激活剂(TPA)的亚阈值剂量已被 以111In-血小板积累量和 125I-纤维蛋白在血管内金属支架上形成的血栓中，或 外置式血管移植物血栓形成节段 慢性动静脉(AV)股分流。溶栓损失有 还检测了预成型的、稳定的、111In-血小板和 ~(125)I-纤维蛋白标记的移植物血栓及相应的增殖 血栓形成的尾巴，连同血栓形成的血液测试的变化， 溶栓止血。静脉推注剂量递增 R-LysPgn(2、4或8 mg/kg)增加循环纤溶酶原水平 以剂量依赖的方式，通过对数线性清除 T50为120min，并反过来减少血栓的堆积 金属支架和血管移植物节段(P&lt；所有病例均为0.001 8毫克/公斤剂量)。R-LysPgn也损害了血小板聚集 在体外对生理激动剂的反应，而不是在体外。 小剂量r-LysPgn(2 mg/kg)大剂量血栓前给药 增强放射性标记非闭塞血栓的溶解作用 亚阈值剂量tPA(0.1 mg/kg)与单纯tPA对照组的比较 (P=0.03)。支架前选择性注射r-LysPgn 展开减少血栓形成的数量，而不影响 通过促进内源性tPA溶栓而止血。R-LysPgn可能 为介入治疗提供安全有效的抗血栓治疗 血管手术。

To enhance thrombolytic responses without increasing hemorrhagic risks, the antithrombotic effects of recombinant Lys-plasminogen (r-LysPgn), a prothrombolytic plasminogen intermediate, have been examined in baboon models of thrombus formation and dissolution. The dose-response effects of r-LysPgn, alone or in combination with sub-threshold dosing of tissue plasminogen activator (tPA), have been measured with respect to the accumulation of 111In-platelets and 125I-fibrin in thrombus forming on endovascular metallic stents, or thrombogenic segments of vascular graft interposed in exteriorized chronic arteriovenous (AV) femoral shunts. Thrombolytic losses have also been determined for preformed, stable, 111In-platelet and 125I-fibrin labeled graft thrombus and corresponding propagated thrombotic tails, together with changes in blood tests of thrombosis, thrombolysis and hemostasis. Escalating doses of bolus intravenous r-LysPgn (2, 4 or 8 mg/kg) increased circulating plasmin ogen levels in a dose-dependent manner, was removed by log-linear clearance with T50 of 120 min, and reciprocally decreased the accumulating thrombus on metallic stents and segments of vascular graft (p<0.001in all cases for 8 mg/kg doses). r-LysPgn also impaired platelet aggregatory responses to physiologic agonists in vitro, but not ex vivo. Prethrombosis administration of low-dose r-LysPgn (2 mg/kg) greatly enhanced the lysis of radiolabeled non-occluding thrombus by a sub-threshold dose of tPA (0.1 mg/kg) compared with tPA-only controls (p=0.03). Elective bolus injections of r-LysPgn prior to stent deployment decrease the amount of thrombus formed without compromising hemostasis by facilitating endogenous tPA thrombolysis. r-LysPgn may provide effective and safe antithrombotic therapy for Interventional vascular procedures.