Nydahl S, Frebelius S, Swedenborg J
Department of Surgery, Karolinska Hospital, Stockholm, Sweden.
Thromb Res. 1992 Feb 1;65(3):365-76. doi: 10.1016/0049-3848(92)90167-9.
A recirculating Langendorff preparation was developed in order to study the effects of antithrombin III (AT) and heparin on thrombin inactivation in the capillary bed. Using this technique, rat hearts were shown to inhibit approximately 50% of the recirculated thrombin, while surface-bound thrombin displayed no enzymatic activity towards recirculated fibrinogen. By displacing thrombin bound to the endothelial surface with Polybrene, thrombin enzymatic activity was found to be equally active against a synthetic chromogenic substrate (S-2238) and fibrinogen. This indicates that thrombin bound to the capillary endothelial surface is not coagulantly active, but, when displaced from the endothelium, its coagulant activity is retained. Hearts pretreated with AT or heparin had no effect on thrombin inhibition or surface-bound thrombin, although there was an uptake of both substances to the heart. These findings are in contrast with the results obtained from large vessel preparations, where pretreatment with AT increased thrombin inhibition and also demonstrated lower levels of surface-bound thrombin, and where heparin eluted endogenous AT from the endothelium. It is concluded that AT plays a more important role in the inhibition of thrombin on large vessels than in the microcapillary system where thrombomodulin is the major inactivator of thrombin.
为了研究抗凝血酶III（AT）和肝素对毛细血管床中凝血酶失活的影响，开发了一种循环式Langendorff灌注制备方法。使用该技术，大鼠心脏可抑制约50%的循环凝血酶，而表面结合的凝血酶对循环纤维蛋白原无酶活性。通过用聚凝胺取代结合在内皮表面的凝血酶，发现凝血酶对合成发色底物（S-2238）和纤维蛋白原具有同等活性。这表明结合在毛细血管内皮表面的凝血酶没有促凝活性，但从内皮上被取代后，其促凝活性得以保留。用AT或肝素预处理的心脏对凝血酶抑制或表面结合的凝血酶没有影响，尽管这两种物质都被心脏摄取。这些发现与从大血管制备中获得的结果相反，在大血管制备中，用AT预处理可增加凝血酶抑制作用，且表面结合的凝血酶水平也较低，并且肝素可从内皮上洗脱内源性AT。结论是，与在微毛细血管系统中凝血调节蛋白是凝血酶的主要失活剂相比，AT在抑制大血管中的凝血酶方面发挥着更重要的作用。
