Effect of the elastase inhibitor eglin C in porcine endotoxin shock.

Abstract

We wanted to demonstrate that the neutrophil elastase inhibitor eglin C reduces the loss of intravascular protein in endotoxin (LPS) shock and that effective concentrations are present in lymph. We used 45 anesthetized miniature pigs in a randomized, controlled trial. LPS 10 micrograms/kg/hr was given for 6 hr. Recombinant eglin C was given before LPS (250 nmol/kg) and continuously at 250 nmol/kg/hr (n = 18); septic controls received saline (n = 18); nine nonseptic controls were used. Eglin C significantly reduced the loss of intravascular protein (plasma volume times plasma protein concentration) from -0.79 g/kg in septic controls to 0.42 g/kg in eglin C-treated animals and reduced plasma concentration of neutrophil elastase, bound to the leukocyte neutral protease inhibitor (LNPI), but systemic hypotension was unchanged. Six additional pigs were anesthetized, prepared with a thoracic lymph fistula, and received eglin C at 475 nmol/kg/hr; three received saline; three received LPS. Eglin C concentrations in lymph were comparable to those in plasma. We conclude that eglin C reduced the loss of intravascular protein during LPS shock and attained effective concentrations in lymph.

• Authors: M Siebeck, H Hoffmann, J Weipert, H Fritz
• Journal: Circulatory shock (Circ Shock) Vol. 36 Issue 3 Pg. 174-9 (Mar 1992) ISSN: 0092-6213 [Print] United States
• PMID: 1351797 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Lipopolysaccharides
• Proteinase Inhibitory Proteins, Secretory
• Proteins
• Recombinant Proteins
• Serine Proteinase Inhibitors
• Serpins
• eglin proteinase inhibitors
• Pancreatic Elastase
• Leukocyte Elastase

Topics

• Animals
• Blood Pressure (drug effects)
• Cardiac Output (drug effects)
• Disease Models, Animal
• Extracellular Space (chemistry)
• Leukocyte Elastase
• Lipopolysaccharides
• Lymph (chemistry, physiology)
• Pancreatic Elastase (blood)
• Proteinase Inhibitory Proteins, Secretory
• Proteins
• Recombinant Proteins (pharmacology)
• Serine Proteinase Inhibitors (blood, pharmacokinetics, pharmacology)
• Serpins
• Shock, Septic (blood, physiopathology)
• Swine