Effect of urokinase on disseminated intravascular coagulation.
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.
Departments of Anesthesiology, Biochemistry, and Surgery, Texas Tech University Health Science Center, El Paso, Texas 79905, USA.
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Vasquez
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Williams
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Hardaway
D000818:Animals; D001794:Blood Pressure; D004211:Disseminated Intravascular Coagulation / Q000097:blood / Q000503:physiopathology / Q000628:therapy*; D004927:Escherichia coli Infections / Q000503:physiopathology*; D005338:Fibrin Fibrinogen Degradation Products / Q000032:analysis; D005340:Fibrinogen / Q000378:metabolism; D006439:Hemodynamics / Q000187:drug effects; D007262:Infusions, Intravenous; D010108:Oxyhemoglobins / Q000378:metabolism; D010976:Platelet Count; D012772:Shock, Septic / Q000097:blood / Q000150:complications* / Q000503:physiopathology; D013318:Stroke Volume; D013552:Swine; D014568:Urokinase-Type Plasminogen Activator / Q000008:administration & dosage / Q000627:therapeutic use*; D014655:Vascular Resistance
D005338:Fibrin Fibrinogen Degradation Products; D010108:Oxyhemoglobins; D005340:Fibrinogen; D014568:Urokinase-Type Plasminogen Activator