Effect of Recombinant Hirudin, a Specific Inhibitor of Thrombin, on Endotoxin-induced Intravascular Coagulation and Acute Lung Injury in Pigs

Endotoxin-induced disseminated intravascular coagulation in rabbits: Effect of recombinant hirudin on hemostatic parameters, fibrin deposits, and mortality

“…These results are in accord with those in previous studies showing that r-hirudin can decrease the consumption of platelets, fibrhaogen, and ATIII, as well as diminishing increases in fibrin monomers, thrombin-antithrombin complexes, fibrinogen-fibrin degradation products, and fibrin deposition in different animal models of endotoxininduced DIC. [22][23][24] Furthermore, a prior study with rabbits infused with gram-negative bacteria showed that mortality in animals treated with r-hirudin and antibiotic was lower than in animals treated with heparin and antibiotic. 25 The improvement in protein C concentration with r-hirudin treatment was remarkable among the changes observed in coagulation parameters.…”

“…17-2° However, human and animal studies have shown that r-hirudin may be useful in the treatment of venous and arterial thrombosis, 21 and experimental models suggest that it may be an attractive agent for treating endotoxin-induced DIC. [22][23][24][25][26] The goal of the present study was to evaluate the effect of different doses of r-hirudin on mortality and kidney fibrin deposition in a rabbit model of endotoxin-induced DIC. As a secondary endpoint, we analyzed the changes in several coagulation-related and fibrinolytic parameters.…”

From clot to collagen: coagulation peptides in interstitial lung disease

“…For example, intravenous administration of fibrin(ogen) degradation products has been shown to lead to increases in endothelial permeability, extravasation of blood proteins, as well as interstitial and alveolar clot formation [12]. Similar lung changes have also been observed following intravenous infusion of thrombin in sheep [13]; whilst thrombin inhibitors have been shown to be efficacious at reducing lung procoagulant activity and alveolar fibrin deposition in animal models of endotoxaemia in pigs [14], as well as reducing the severity of acute lung injury in newborn piglets [15], although the final outcome of the lesion obtained in this particular model was not reported. Taken together, these studies suggest an important role for these proteins in the pathophysiology of these conditions.…”

Pathophysiology of Shock, Sepsis, and Organ Failure

“…These results could be clearly confirmed in a second randomized trial, in which the release of the porcine PMN constituents were highly correlated with the occurrence of hypotension and hypoproteinemia due to infusion of viable bacteria . In another prospectively controlled, randomized, short-term study performed by our research group (Hoffmann et al 1990), a similar significant increase of PMN elastase in complex with LNPI to above normal was noticed concomitant with the development of organ dysfunctions in 18 pigs receiving a continuous infusion of S. abortus equi endotoxin over the whole observation period of 6 h. No such changes occurred in sham-treated control animals.…”

“…Moreover, in a further controlled investigation, Siebeck et al (1989c) and Hoffmann et al (1990) could show that, besides eglin c, the thrombinspecific inhibitor hirudin -another recombinant inhibitor also formerly isolated from the medical leech -significantly improved endotoxin shock syndromes in minipigs. Fibrinogen consumption, formation of fibrin monomers, the occurrence of pulmonary vasoconstriction, and the release of PMN constituents were clearly lower in endotoxemic animals treated prophylactically with hirudin than in those without continuous intravenous inhibitor infusion.…”