Mammen E F, Miyakawa T, Phillips T F, Assarian G S, Brown J M, Murano G
Semin Thromb Hemost. 1985 Oct;11(4):373-83. doi: 10.1055/s-2007-1004397.
The effect of human antithrombin III concentrates was studied in a dog model in which DIC was produced by the infusion of 0.66 M lactic acid. In 35 animals infused with lactic acid only, platelet counts, fibrinogen levels, alpha 2-antiplasmin levels, and antithrombin levels decreased significantly over a 4-hour observation period. At the same time, the levels of fibrin(ogen) split products increased. At the end of the experimental period, the glomeruli of the dogs' kidneys contained significant quantities of fibrin. Hemodynamically, the dogs experienced a significant decrease in cardiac output, whereas the mean arterial blood pressures remained unchanged. Urine output seemed to decline during the time of study. Appreciable quantities of heparin could be measured in the dogs' plasmas. In 13 dogs that were treated in the same manner as the just described 35 animals, 1 U of human antithrombin concentrate per ml of calculated dog plasma was infused over a 90-minute time span, beginning after 1 hour of acidosis. Although no differences were noted in the decrease in platelet counts between the two groups, fibrinogen levels and alpha 2-antiplasmin levels declined less drastically in the antithrombin-treated group. Also the levels of fibrin(ogen) split products increased less in the treated group. The antithrombin activity levels increased markedly and remained at their high levels even after the infusion of antithrombin had ceased. The amount of human antithrombin circulating was followed by immunologic assays using a human antibody to antithrombin. Also, with this technique, the levels of infused antithrombin did not decrease. The amount of fibrin found in the glomeruli of this group of animals was significantly lower than in the nontreated group (p less than 0.001). Even cardiac output was higher in the treated group and urine production seemed to increase. Also, these dogs had appreciable quantities of heparin in their plasmas. In a control group of six animals who were infused with saline instead of lactic acid, no major changes were observed in the coagulation and cardiovascular parameters. These data seem to suggest that antithrombin concentrates exert a certain protective effect in this particular DIC animal model.
在通过输注0.66M乳酸诱导弥散性血管内凝血（DIC）的犬模型中研究了人抗凝血酶III浓缩物的作用。在仅输注乳酸的35只动物中，在4小时的观察期内血小板计数、纤维蛋白原水平、α2 -抗纤溶酶水平和抗凝血酶水平显著下降。同时，纤维蛋白（原）降解产物水平升高。在实验期结束时，犬肾的肾小球含有大量纤维蛋白。血流动力学方面，犬的心输出量显著下降，而平均动脉血压保持不变。在研究期间尿量似乎减少。在犬的血浆中可检测到相当数量的肝素。在以与上述35只动物相同方式处理的13只犬中，在酸中毒1小时后开始，在90分钟内每毫升计算的犬血浆输注1单位人抗凝血酶浓缩物。尽管两组之间血小板计数下降没有差异，但在抗凝血酶治疗组中纤维蛋白原水平和α2 -抗纤溶酶水平下降幅度较小。而且治疗组中纤维蛋白（原）降解产物水平升高也较少。抗凝血酶活性水平显著升高，甚至在抗凝血酶输注停止后仍保持在高水平。使用抗人抗凝血酶抗体通过免疫测定法追踪循环中的人抗凝血酶量。同样，用这种技术，输注的抗凝血酶水平没有下降。该组动物肾小球中发现的纤维蛋白量明显低于未治疗组（p小于0.001）。甚至治疗组的心输出量更高，尿量似乎增加。而且，这些犬的血浆中含有相当数量的肝素。在输注生理盐水而非乳酸的6只动物的对照组中，凝血和心血管参数未观察到重大变化。这些数据似乎表明抗凝血酶浓缩物在这个特定的DIC动物模型中发挥了一定的保护作用。
