Low doses of endotoxin potentiate venous thrombosis in the rabbit.
Procoagulant activity of the endothelium and of monocytes was induced by an intravenous administration of a low dose of endotoxin in the rabbit. Venous thrombosis induced by a 45-min stasis of the jugular vein was dramatically increased after the administration of endotoxin. Endotoxin enhanced venous thrombosis in a dose-dependent manner which was the highest after the administration of 1 microgram/kg. This effect increased with time but was optimal when endotoxin was injected 4 h before stasis induction. Leukocytes appear to play a key role in this process since mechlorethamine-induced leukopenia totally inhibited thrombus formation. Hirudin and heparin, administered intravenously 5 min before stasis, were both potent inhibitors of endotoxin-induced venous thrombosis exhibiting ED50 values of 3.8 +/- 1.0 and 2.3 +/- 1.1 microgram/kg, respectively.
Bernat
A
A
Sanofi Recherche Haemobiology Research Department, Toulouse, France.
Sainte-Marie
M
M
Roque
C
C
Ingelaere
V
V
Maffrand
J P
JP
Herbert
J M
JM
D000818:Animals; D004305:Dose-Response Relationship, Drug; D006487:Hemostasis / Q000187:drug effects; D006493:Heparin / Q000494:pharmacology; D006629:Hirudins / Q000494:pharmacology; D007601:Jugular Veins; D007970:Leukopenia / Q000139:chemically induced / Q000150:complications; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D008466:Mechlorethamine; D008855:Microscopy, Electron, Scanning; D011817:Rabbits; D013921:Thrombocytopenia / Q000150:complications; D013927:Thrombosis / Q000139:chemically induced*
D006629:Hirudins; D008070:Lipopolysaccharides; D008466:Mechlorethamine; D006493:Heparin