Inauen W, Baumgartner H R, Bombeli T, Haeberli A, Straub P W
Department of Internal Medicine, University Hospital, Inselspital, Bern, Switzerland.
Arteriosclerosis. 1990 Jul-Aug;10(4):607-15. doi: 10.1161/01.atv.10.4.607.
The effect of heparin on thrombogenesis induced by the subendothelium of rabbit aorta was investigated in 24 healthy volunteers after intravenous injection of different doses (0, 1000, 2500, and 5000 IU). By using an ex vivo perfusion chamber system, the interaction between flowing blood and exposed subendothelium was measured at low (50 s-1), intermediate (650 s-1), and high (2600 s-1) wall shear rates. The low shear rate simulated blood flow in venous, the intermediate shear rate in arterial, and the high shear rate in small or stenosed arterial vessels. Deposition of fibrin, platelets, and platelet thrombi on vascular subendothelium (SE) was quantified by morphometrical and immunological techniques. Fibrin deposition prevailed at low shear rates and was only minimal at high shear rates (30 +/- 1% vs. 1 +/- 0.4% coverage of SE with fibrin, means +/- SEM, p less than 0.001). In contrast, the interaction of platelets with SE was more intense at high compared to low shear rates, as indicated by higher platelet adhesion (54 +/- 5% vs. 4 +/- 1% coverage of SE with platelets, p less than 0.001) and platelet thrombus volumes (4.8 +/- 1.3 vs. 0.5 +/- 0.1 microns 3/microns 2, p less than 0.001). Fibrin deposition on SE was inhibited by heparin in a dose-dependent manner and was abolished after high doses. In addition, high doses of heparin reduced the height and volume of platelet thrombi at low and intermediate wall shear rates, but no effect was found at the high shear rate. Our data show that heparin inhibits the formation of both fibrin and platelet thrombi on vascular subendothelium. The lack of effect of heparin on platelet thrombus formation at high shear rates indicates that thrombin modulates the growth rate and/or stability of platelet thrombi at low and intermediate shear rates, whereas additional factors may control platelet thrombus growth and stability at high shear conditions.
在24名健康志愿者静脉注射不同剂量（0、1000、2500和5000国际单位）肝素后，研究了肝素对兔主动脉内皮下层诱导的血栓形成的影响。通过使用离体灌注腔系统，在低（50秒⁻¹）、中（650秒⁻¹）和高（2600秒⁻¹）壁剪切率下测量流动血液与暴露的内皮下层之间的相互作用。低剪切率模拟静脉中的血流，中剪切率模拟动脉中的血流，高剪切率模拟小动脉或狭窄动脉血管中的血流。通过形态计量学和免疫学技术对纤维蛋白、血小板和血小板血栓在血管内皮下层（SE）的沉积进行定量。纤维蛋白沉积在低剪切率时占主导，在高剪切率时仅为微量（纤维蛋白覆盖SE的比例分别为30±1%和1±0.4%，均值±标准误，p<0.001）。相反，与低剪切率相比，高剪切率时血小板与SE的相互作用更强，表现为更高的血小板黏附（血小板覆盖SE的比例分别为54±5%和4±1%，p<0.001）和血小板血栓体积（分别为4.8±1.3和0.5±0.1立方微米/平方微米，p<0.001）。肝素以剂量依赖的方式抑制纤维蛋白在SE上的沉积，高剂量时可消除这种沉积。此外，高剂量肝素在低和中壁剪切率下降低了血小板血栓的高度和体积，但在高剪切率下未发现影响。我们的数据表明肝素抑制血管内皮下层上纤维蛋白和血小板血栓的形成。肝素在高剪切率下对血小板血栓形成缺乏影响表明，凝血酶在低和中剪切率下调节血小板血栓的生长速率和/或稳定性，而在高剪切条件下可能有其他因素控制血小板血栓的生长和稳定性。
