Effect of Recombinant Hirudin, a Specific Inhibitor of Thrombin, on Endotoxin-induced Intravascular Coagulation and Acute Lung Injury in Pigs
| Autor: | Matthias Siebeck, Hans Fritz, Marion Weis, Hans Hoffmann, Marianne Jochum, Michael Spannagl, Reinhard Geiger |
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| Rok vydání: | 1990 |
| Předmět: |
Pulmonary and Respiratory Medicine
Neutrophils Swine medicine.medical_treatment Antithrombin III Hirudin Pharmacology Lung injury Fibrinogen Thrombin Salmonella Leukocytes Coagulopathy medicine Animals Protease Inhibitors Lung Saline Pancreatic Elastase business.industry Hemodynamics Hirudins medicine.disease Recombinant Proteins Blood Cell Count Endotoxins medicine.anatomical_structure Coagulation Anesthesia Acute Disease Swine Miniature Prothrombin business medicine.drug |
| Zdroj: | American Review of Respiratory Disease. 142:782-788 |
| ISSN: | 0003-0805 |
| Popis: | We hypothesized that thrombin activation may play a prominent role in endotoxin-induced secondary organ failure, such as acute lung injury. To test this hypothesis, we administered a thrombin-specific inhibitor, recombinant hirudin, in endotoxemic pigs. The pigs were anesthetized, mechanically ventilated, and prepared with Swan-Ganz and extravascular lung water (EVLW) catheters. A total of 18 randomly selected animals received a pretreatment of 1,000 U/kg of hirudin, followed by a continuous infusion over 6 h of 500 U/kg/h given simultaneously with the infusion of 10 micrograms/kg/h of Salmonella abortus equi endotoxin. Another 18 animals received a continuous infusion over 6 h of endotoxin but did not receive hirudin. All animals were fluid resuscitated with 17 ml/kg/h of saline for the duration of the experiment. Data are expressed as the mean (95% confidence interval). Hirudin reduced the endotoxin-induced consumption of plasma fibrinogen from -110 (-138 to -82) mg/100 ml to -39 (-67 to -12) mg/100 ml (p = 0.0001) and endotoxin-induced increases in the soluble fibrin in plasma from 434 (369 to 499) ng/ml to 236 (171 to 300) ng/ml (p = 0.0002). These data suggest an effective inhibition of the endotoxin-generated thrombin by hirudin. Furthermore, hirudin significantly reduced endotoxin-induced increases in pulmonary vascular resistance from 32 (27 to 37) kdyn x s x cm-5 x kg to 20 (15 to 25) kdyn x s x cm-5 x kg (p = 0.0015) and increases in EVLW from 15.4 (13.2 to 17.6) ml/kg to 12.2 (10.0 to 14.4) ml/kg (p = 0.0299).(ABSTRACT TRUNCATED AT 250 WORDS) |
| Databáze: | OpenAIRE |
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