Delayed treatment with desulfato-hirudin prevents fibrin formation in lipopolysaccharide-induced shock.
Previous work has shown that pre-treatment with the thrombin inhibitor recombinant desulfato-hirudin prevented fibrin formation and respiratory dysfunction in porcine lipopolysaccharide shock. We examined the effects of delayed administration of recombinant desulfato-hirudin in bacterial lipopolysaccharide shock. Miniature pigs were studied under anaesthesia and ventilation, and received a bacterial lipopolysaccharide infusion (2 microg/kg/h) for 7 h; recombinant desulfato-hirudin was started 1 h after bacterial lipopolysaccharide in 10 animals (bolus 12.9 nmol/kg; continuous infusion 6.5 nmol/ kg/h); 10 randomised control animals received saline instead of recombinant desulfato-hirudin. Fibrin and thrombin-antithrombin complex levels in plasma were significantly lower in bacterial lipopolysaccharide+recombinant desulfato-hirudin animals than in controls. Both groups displayed a similar rise in pulmonary vascular resistance and other parameters of lung dysfunction; only lung tissue wet/dry ratio was lower in recombinant desulfato-hirudin-treated than in control animals. Both groups had similar circulatory alterations. Recombinant desulfato-hirudin interrupted coagulation activation during ongoing bacterial lipopolysaccharide-induced shock in pigs even when administered with a delay of one hour after start of the bacterial lipopolysaccharide infusion. A protective effect of delayed recombinant desulfato-hirudin administration on bacterial lipopolysaccharide-induced acute lung injury and alterations in the systemic circulation could not be demonstrated in this experiment.
Siebeck
M
M
Department of Surgery, Klinikum Innenstadt, Ludwig-Maximilians University, Munich, Germany. m.siebeck@lrz.uni-muenchen.de
Spannagl
M
M
Bichler
J
J
Hoffmann
H
H
Gippner-Steppert
C
C
Jochum
M
M
D000818:Animals; D001201:Ascites; D002319:Cardiovascular System / Q000187:drug effects; D005337:Fibrin / Q000096:biosynthesis*; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D024764:Hirudin Therapy; D006629:Hirudins / Q000031:analogs & derivatives*; D007668:Kidney / Q000187:drug effects; D008070:Lipopolysaccharides; D008168:Lung / Q000187:drug effects; D010529:Peritoneal Cavity; D011994:Recombinant Proteins / Q000627:therapeutic use; D012772:Shock, Septic / Q000188:drug therapy*; D013552:Swine; D013556:Swine, Miniature; D013997:Time Factors
D005343:Fibrinolytic Agents; D006629:Hirudins; D008070:Lipopolysaccharides; D011994:Recombinant Proteins; D005337:Fibrin; C060225:desirudin