Dickneite G, Pâques E P
Research Laboratories, Behringwerke AG, Marburg/Lahn, Germany.
Thromb Haemost. 1993 Feb 1;69(2):98-102.
Experimental gram-negative sepsis was induced in the rat by Klebsiella pneumoniae. Although bacteria are susceptible to the treatment with the antibiotic Tobramycin, DIC could not be prevented. DIC was manifested by a leuko- and thrombocytopenia, decreases in fibrinogen and AT III and an increase of the aPTT. In this model the therapeutic treatment with human AT III was evaluated. To determine the optimal concentration of AT III a prestudy in a LPS induced DIC in the rat was performed. It was shown that a bolus i.v. injection of 500 U/kg improved survival and DIC, and was thus chosen for the Klebsiella sepsis model. The infectious load was adjusted to yield a mortality rate of 90-100% in the untreated Klebsiella group and a reduction to about 40-50% of the mortality rate by Tobramycin. It was found that AT III reduced mortality in the Klebsiella induced sepsis not only when given prophylactically but was effective even when administrated in a late stage of the DIC, i.e. 3 or 5 h post infection.
通过肺炎克雷伯菌在大鼠中诱导实验性革兰氏阴性败血症。尽管细菌对妥布霉素治疗敏感，但无法预防弥散性血管内凝血（DIC）。DIC表现为白细胞减少和血小板减少、纤维蛋白原和抗凝血酶III（AT III）降低以及活化部分凝血活酶时间（aPTT）增加。在该模型中评估了用人AT III进行的治疗。为了确定AT III的最佳浓度，在大鼠内毒素诱导的DIC中进行了一项预研究。结果表明，静脉推注500 U/kg可提高生存率并改善DIC，因此在肺炎克雷伯菌败血症模型中选择了该剂量。调整感染负荷，使未治疗的肺炎克雷伯菌组死亡率达到90 - 100%，妥布霉素可将死亡率降低至约40 - 50%。研究发现，AT III不仅在预防性给药时可降低肺炎克雷伯菌诱导的败血症死亡率，而且在DIC后期（即感染后3或5小时）给药也有效。
