Endotoxin-induced intravascular coagulation in rabbits: effect of tissue plasminogen activator vs urokinase of PAI generation, fibrin deposits and mortality.
We have evaluated the effect of plasminogen activators (t-PA and urokinase) on an experimental model of disseminated intravascular coagulation (DIC) in rabbits by injection of 20 micrograms/kg/h of E. coli lipopolysaccharide during 6 h t-PA (0.2 mg/kg and 0.7 mg/kg), urokinase (3000 U/kg/h) and saline (control) were given simultaneously with endotoxin. Results indicated that urokinase and low dose of t-PA significantly reduced the increase of plasminogen activator inhibitor (PAI) activity observed 2 h after endotoxin (p < 0.001). High t-PA dose also diminished the PAI levels at 6 h (p < 0.001). A significant reduction of fibrin deposits in kidneys was observed din both t-PA treated groups as compared with findings in the group of rabbits infused with saline solution (p < 0.005), whereas urokinase had no significant effect on the extent of fibrin deposition. Finally, the mortality rate in the control group (70%) was reduced to 50% in rabbits receiving high doses of t-PA. In conclusion, treatment with t-PA resulted in reduced PAI generation, fibrin deposits and mortality in endotoxin-treated rabbits.
Paloma
M J
MJ
Hematology Service, University Clinic of Navarra, Pamplona, Spain.
Páramo
J A
JA
Rocha
E
E
D000818:Animals; D004195:Disease Models, Animal; D004211:Disseminated Intravascular Coagulation / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy*; D005337:Fibrin / Q000378:metabolism*; D005342:Fibrinolysis / Q000187:drug effects; D008070:Lipopolysaccharides; D008297:Male; D010960:Plasminogen Activators / Q000627:therapeutic use*; D015849:Plasminogen Inactivators / Q000096:biosynthesis*; D011817:Rabbits; D015996:Survival Rate; D010959:Tissue Plasminogen Activator / Q000627:therapeutic use*; D014568:Urokinase-Type Plasminogen Activator / Q000627:therapeutic use*
D008070:Lipopolysaccharides; D015849:Plasminogen Inactivators; D005337:Fibrin; D010960:Plasminogen Activators; D010959:Tissue Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator