title: The elastase-inhibitor eglin has no effect in an ovine model of endotoxemia.
abstract: Small doses of endotoxin have been shown to induce pulmonary microvascular injury in sheep, possibly by the action of granulocytes. Eglin, a potent inhibitor of neutrophil elastase, was tested in an ovine model of endotoxemia. The experiment was performed in 12 unanesthetized chronically instrumented sheep with a lung lymph preparation. Endotoxin (S. abort. equii) was infused at 24 ng/(kg x h) with application of 20 mg/kg eglin 1 h before endotoxin in the treatment group and followed by 5 mg/(kg x h). No significant improvement due to the treatment was seen for either cardiovascular status (pulmonary and systemic vascular resistance) or permeability changes in the lung (lymph flow and lymph/plasma protein ratio), although sufficient eglin concentrations were achieved in plasma and lymph. The lack of an effect of eglin might be because higher concentrations are needed to block elastase-like activity of ovine granulocytes or because of a minor role for neutrophil elastase in this shock model.
authors.affiliation: Ludwig-Boltzmann-Institut für experimentelle Traumatologie, Wien.
authors.forename: H
authors.initials: H
authors.lastname: Redl
authors.forename: G
authors.initials: G
authors.lastname: Schlag
authors.forename: C
authors.initials: C
authors.lastname: Vogl
authors.forename: A
authors.initials: A
authors.lastname: Schiesser
authors.forename: E
authors.initials: E
authors.lastname: Paul
authors.forename: M
authors.initials: M
authors.lastname: Thurnher
authors.forename: W
authors.initials: W
authors.lastname: Junger
authors.forename: L D
authors.initials: LD
authors.lastname: Traber
authors.forename: D L
authors.initials: DL
authors.lastname: Traber
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D004731:Endotoxins; D004926:Escherichia coli; D006098:Granulocytes / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D007958:Leukocyte Count; D008208:Lymphatic System / Q000187:drug effects; D010196:Pancreatic Elastase / Q000037:antagonists & inhibitors*; D011506:Proteins / Q000493:pharmacokinetics / Q000627:therapeutic use*; D015843:Serpins; D012756:Sheep; D013929:Thromboxane B2 / Q000097:blood; D014115:Toxemia / Q000188:drug therapy*
chemical_list: D004731:Endotoxins; D011506:Proteins; D015843:Serpins; C028656:eglin proteinase inhibitors; D013929:Thromboxane B2; D010196:Pancreatic Elastase