Effect of the elastase inhibitor eglin C in porcine endotoxin shock.
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.
Chirurgische Klinik und Poliklinik, Abteilung für Klinische Chemie Ludwig-Maximilians-Universität, Munich, Federal Republic of Germany.
M
M
Siebeck
H
H
Hoffmann
J
J
Weipert
H
H
Fritz
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D004195:Disease Models, Animal; D005110:Extracellular Space / Q000737:chemistry; D019272:Leukocyte Elastase; D008070:Lipopolysaccharides; D008196:Lymph / Q000737:chemistry / Q000502:physiology; D010196:Pancreatic Elastase / Q000097:blood; D053491:Proteinase Inhibitory Proteins, Secretory; D011506:Proteins; D011994:Recombinant Proteins / Q000494:pharmacology; D015842:Serine Proteinase Inhibitors / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D015843:Serpins; D012772:Shock, Septic / Q000097:blood / Q000503:physiopathology*; D013552:Swine
D008070:Lipopolysaccharides; D053491:Proteinase Inhibitory Proteins, Secretory; D011506:Proteins; D011994:Recombinant Proteins; D015842:Serine Proteinase Inhibitors; D015843:Serpins; C028656:eglin proteinase inhibitors; D010196:Pancreatic Elastase; D019272:Leukocyte Elastase