Dickneite G, Czech J
Research Laboratories of Behringwerke AG, Marburg, Germany.
Thromb Haemost. 1994 Jun;71(6):768-72.
Rats which were infected with the gramnegative pathogen Klebsiella pneumoniae develop disseminated intravascular coagulation (DIC), multi-organ failure (MOF) and finally die in a septic shock. We investigated the therapeutic effect of antibiotic (tobramycin) treatment combined with the infusion of the highly specific thrombin inhibitor rec. hirudin. Although administration of 2 mg/kg tobramycin alone leads to a decrease of the bacterial burden, DIC could not be prevented. Infusion of rec. hirudin (0.25 mg/kg x h) for 4 h (start of treatment 1 h post infection), in addition to a bolus administration of tobramycin, led to an amelioration of DIC parameters as fibrinogen, thrombin-antithrombin complex (TAT) and platelets. Serum transaminase levels (GOT, GPT) as a marker of MOF were significantly improved by rec. hirudin, the T50 value increased from 17 h in the tobramycin group to 42 h in the tobramycin+rec. hirudin group, mortality rates were 90% or 60%, respectively. Combination of heparin (100 U/kg x h) and tobramycin was not effective on survival.
感染革兰氏阴性病原体肺炎克雷伯菌的大鼠会发生弥散性血管内凝血（DIC）、多器官功能衰竭（MOF），最终死于感染性休克。我们研究了抗生素（妥布霉素）治疗联合输注高度特异性凝血酶抑制剂重组水蛭素的治疗效果。尽管单独给予2mg/kg妥布霉素可导致细菌负荷降低，但无法预防DIC。除了给予一次大剂量的妥布霉素外，输注重组水蛭素（0.25mg/kg·h）4小时（感染后1小时开始治疗）可改善DIC参数，如纤维蛋白原、凝血酶-抗凝血酶复合物（TAT）和血小板。作为MOF标志物的血清转氨酶水平（GOT、GPT）通过重组水蛭素得到显著改善，T50值从妥布霉素组的17小时增加到妥布霉素+重组水蛭素组的42小时，死亡率分别为90%或60%。肝素（100U/kg·h）与妥布霉素联合使用对生存率无效。
