Inhibition of plasma kallikrein with aprotinin in porcine endotoxin shock
Autor: | Michael Spannagl, Matthias Siebeck, Hans Fritz, Marianne Jochum, Leonhard Schweiberer, Weipert J, Peter Kroworsch, Kazuaki Shimamoto, Edwin Fink |
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Rok vydání: | 1993 |
Předmět: |
Lipopolysaccharides
medicine.medical_specialty Lipopolysaccharide Swine Radioimmunoassay Blood Pressure Critical Care and Intensive Care Medicine Iodine Radioisotopes chemistry.chemical_compound Aprotinin Internal medicine medicine Animals Blood Coagulation Complement Activation Lung Compliance Kininogen Septic shock business.industry Kininogens Kallikrein Kinin medicine.disease Shock Septic Endocrinology chemistry Coagulation Shock (circulatory) Immunology Complement C3a Swine Miniature Surgery Kallikreins medicine.symptom business circulatory and respiratory physiology medicine.drug |
Zdroj: | Europe PubMed Central |
ISSN: | 0022-5282 |
Popis: | Activation of the contact phase of coagulation has been implicated in the pathogenesis of septic shock. We wanted to determine if inhibition of plasma kallikrein can prevent arterial hypotension and liberation of kinins from kininogen, induced by an infusion of bacterial lipopolysaccharide (LPS) in anesthetized, ventilated 20-kg pigs. The LPS was given IV in a dose of 5 micrograms/kg/h for 8 hours. The plasma kallikrein inhibitor aprotinin, 537 mumol, was given IV during 8 hours, resulting in plasma levels above 10 mumol/L. Ten animals (SA) received LPS and aprotinin and ten randomized controls (SC) received LPS and saline. Kinin-containing kininogen was determined on the basis of the amount of kinin releasable in plasma samples by incubation with trypsin. Kininogen decreased to 58% +/- 4% of the baseline value without any difference between groups. This may indicate participation of other processes than degradation by plasma kallikrein in the decrease of kininogen. Arterial blood pressure was higher at 7 hours in the SA animals than in the SC group (101% +/- 11% vs. 68% +/- 8%; mean +/- SEM; p = 0.026). Fibrin monomer and C3adesArg plasma levels were attenuated by aprotinin treatment. These findings underscore the important role of the contact system in LPS shock. |
Databáze: | OpenAIRE |
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