Simmons C A, Burdick M D, Schaub R G
Atherosclerosis & Thrombosis Research, Upjohn Company, Kalamazoo, Michigan 49001.
J Surg Res. 1987 Nov;43(5):468-75. doi: 10.1016/0022-4804(87)90106-5.
Previous studies with models of deep-vein thrombosis (DVT) have demonstrated that leukocyte (PMN)-mediated vein injury may be an initiating event in DVT (14, 17). Since heparin (H) can prevent DVT, we studied its effect on vascular injury and thrombosis in our model. Three groups of rabbits were treated with H either sc (73 and 147 U/kg) or iv (662 U/kg). Scanning electron microscopy revealed that the 73 U/kg sc dose was ineffective. All veins had PMN accumulation, fibrin deposition and complex thrombus formation. There was no increase in anti-Xa activity; activated partial thromboplastin times (APTT) and whole blood clotting times were normal. The 147 U/kg sc and the intravenous dose did not inhibit PMN-mediated vein injury. The endothelium was sloughed by migrating PMNs, basement membrane was exposed, and platelets adhered to it. Thrombosis was completely absent in the iv dose group. This correlated with increased anti-Xa activity and prolonged APTT and whole blood clotting times. Our results indicate that heparin does not inhibit the PMN adhesion and migration which produces vascular injury. However, the anticoagulant activity of heparin effectively reduces fibrin deposition and complex thrombus formation.
先前针对深静脉血栓形成（DVT）模型的研究表明，白细胞（PMN）介导的静脉损伤可能是DVT的起始事件（14, 17）。由于肝素（H）可预防DVT，我们在我们的模型中研究了其对血管损伤和血栓形成的影响。三组兔子分别接受皮下注射（73和147 U/kg）或静脉注射（662 U/kg）的肝素治疗。扫描电子显微镜显示，73 U/kg的皮下注射剂量无效。所有静脉均有PMN聚集、纤维蛋白沉积和复合血栓形成。抗Xa活性未增加；活化部分凝血活酶时间（APTT）和全血凝固时间正常。147 U/kg的皮下注射剂量和静脉注射剂量均未抑制PMN介导的静脉损伤。内皮细胞被迁移的PMN剥脱，基底膜暴露，血小板粘附其上。静脉注射剂量组完全没有血栓形成。这与抗Xa活性增加以及APTT和全血凝固时间延长相关。我们的结果表明，肝素不会抑制产生血管损伤的PMN粘附和迁移。然而，肝素的抗凝活性可有效减少纤维蛋白沉积和复合血栓形成。
