Vasquez Y, Williams C H, Hardaway R M
Departments of Anesthesiology, Biochemistry, and Surgery, Texas Tech University Health Science Center, El Paso, Texas 79905, USA.
J Appl Physiol (1985). 1998 Oct;85(4):1421-8. doi: 10.1152/jappl.1998.85.4.1421.
Our study evaluated the possible therapeutic effect of urokinase in treating the microthrombiotic effects of disseminated intravascular coagulation by assisting the activation of endogenous plasminogen. Twenty-six pigs were anesthetized, intubated, mechanically ventilated, and surgically catheterized. Septic shock was induced in all 26 pigs by an intravenous infusion of heat-killed Escherichia coli. The pigs were divided into two sets of experiments: in experiment 2 (n = 14), one-half received an intravenous dose of urokinase 1 h after heat-killed E. coli infusion and in experiment 3 (n = 12) one-half received an intravenous bolus dose and a continuous drip of urokinase 2 h after heat-killed E. coli infusion. The untreated pigs served as controls. Hemodynamic parameters, blood chemistries, and blood gases were analyzed. Urokinase given 1 h after bacterial toxin infusion significantly restored blood flow, resulting in an increase in cardiovascular and pulmonary function and improved survival rate (43% control vs. 100% treated, 24-h experimental period). Treatment given after 2 h showed some significant effect on pulmonary function; however, within 10 h of E. coli infusion, mortality rates in control and treated groups were 100 and 83%, respectively. Early administration of urokinase after onset of disseminated intravascular coagulation restored blood flow and helped resolve organ damage.
我们的研究评估了尿激酶通过协助激活内源性纤溶酶原，在治疗弥散性血管内凝血的微血栓形成效应方面可能的治疗作用。26只猪被麻醉、插管、机械通气并进行手术置管。通过静脉输注热灭活的大肠杆菌，在所有26只猪中诱发感染性休克。这些猪被分为两组实验：在实验2（n = 14）中，一半猪在输注热灭活大肠杆菌1小时后静脉注射尿激酶；在实验3（n = 12）中，一半猪在输注热灭活大肠杆菌2小时后静脉推注并持续滴注尿激酶。未治疗的猪作为对照。分析了血流动力学参数、血液化学指标和血气。在细菌毒素输注1小时后给予尿激酶可显著恢复血流，导致心血管和肺功能增强，并提高生存率（24小时实验期内，对照组为43%，治疗组为100%）。2小时后给予治疗对肺功能有一些显著影响；然而，在大肠杆菌输注后10小时内，对照组和治疗组的死亡率分别为100%和83%。在弥散性血管内凝血发作后早期给予尿激酶可恢复血流并有助于解决器官损伤。
