DELAYED TREATMENT WITH DESULFATO-HIRUDIN PREVENTS FIBRIN FORMATION INLIPOPOLYSACCHARIDE-INDUCED SHOCK

Previous work has shown that pre-treatment with the thrombin inhibitor recombinant desulfatohirudin prevented fibrin formation and respirato ry dysfunction in porcine lipopolysaccharide shock. We examined the ef fects of delayed administration of recombinant desulfato-hirudin in ba cterial lipopolysaccharide shock. Miniature pigs were studied under an aesthesia and ventilation, and received a bacterial lipopolysaccharide infusion (2 mu g/kg/h) for 7 h; recombinant desulfato-hirudin was sta rted 1 h after bacterial lipopolysaccharide in 10 animals (bolus 12.9 nmol/kg; continuous infusion 6.5 nmol/kg/h); 10 randomised control ani mals received saline instead of recombinant desulfato-hirudin. Fibrin and thrombin-antithrombin complex levels in plasma were significantly lower in bacterial lipopolysaccharide + recombinant desulfato-hirudin mals than in controls. Both groups displayed a similar rise in pulmona ry vascular resistance and other parameters of lung dysfunction; only lung tissue wet/dry ratio was lower in recombinant desulfato-hirudin-t reated than in control animals. Both groups had similar circulatory al terations. Recombinant desulfato-hirudin interrupted coagulation activ ation during ongoing bacterial lipopolysaccharide-induced shock in pig s even when administered with a delay of one hour after start of the b acterial lipopolysaccharide infusion. A protective effect of delayed r ecombinant desulfato-hirudin administration on bacterial lipopolysacch aride-induced acute lung injury and alterations in the systemic circul ation could not be demonstrated in this experiment. (C) 1998 Elsevier Science Ltd.