Paloma M J, Páramo J A, Rifón J, Rocha E
Servicio de Hematología, Clínica Universitaria, Facultad de Medicina, Universidad de Navarra, Pamplona.
Sangre (Barc). 1992 Dec;37(6):435-8.
To assess the therapeutic efficacy of agents capable of stimulating the fibrinolytic system, such as tissue plasminogen activator (t-PA) and urokinase (UK) on endotoxin-induced disseminated intravascular coagulation (DIC) in the rabbit.
DIC was induced by intravenous administration of endotoxin, 20 micrograms/kg/hr during 6 hr. Four different groups were established: a) control group, receiving only saline solution; b) t-PA group receiving 0.2 mg/kg; c) t-PA group receiving 0.7 mg/kg, and d) UK group, which was given 3,000 IU/kg/hr for 6 hr. Blood samples were drawn before and after 2 hr and 6 hr of endotoxin administration. Platelet count, and fibrinogen, factor XII and antithrombin III concentrations, were assessed in each sample. Mean, standard deviation and percentage of increase or decrease with respect to the basal value, this considered 100%, were used to evaluate the findings. For comparison of values, Student's t and Mann Whitney's U were used; the Fisher test was used for mortality studies.
No statistical differences appeared for any of the values in the rabbits under basal conditions. The rabbits in the control group developed DIC. No doses of t-PA modified the changes appearing in blood coagulation. UK reduced the fibrinogen and factor XII consumption induced by endotoxin. The mortality rate in the control group reached 70%. High-dose t-PA decreased such figure to 50%, while low-dose t-PA or UK failed to reduce mortality.
High-dose t-PA has beneficial effects on endotoxin-induced DIC in rabbits. UK failed to achieve such effect at the doses given in this experimental DIC model.
评估能够刺激纤溶系统的药物,如组织型纤溶酶原激活剂(t-PA)和尿激酶(UK)对兔内毒素诱导的弥散性血管内凝血(DIC)的治疗效果。
通过静脉注射内毒素诱导DIC,持续6小时,剂量为20微克/千克/小时。设立四个不同的组:a)对照组,仅接受生理盐水;b)t-PA组,接受0.2毫克/千克;c)t-PA组,接受0.7毫克/千克;d)UK组,给予3000国际单位/千克/小时,持续6小时。在内毒素给药前以及给药2小时和6小时后采集血样。评估每个样本中的血小板计数、纤维蛋白原、因子XII和抗凝血酶III浓度。使用平均值、标准差以及相对于基础值(视为100%)的增减百分比来评估结果。为比较数值,使用学生t检验和曼-惠特尼U检验;使用费舍尔检验进行死亡率研究。
在基础条件下,兔的任何数值均未出现统计学差异。对照组的兔发生了DIC。任何剂量的t-PA均未改变凝血过程中出现的变化。UK减少了内毒素诱导的纤维蛋白原和因子XII消耗。对照组的死亡率达到70%。高剂量t-PA将该数字降至50%,而低剂量t-PA或UK未能降低死亡率。
高剂量t-PA对兔内毒素诱导的DIC具有有益作用。在本实验性DIC模型中给予的剂量下,UK未能达到此效果。