title: Local proteolytic activation after pulmonary trauma is not prevented by high dose steroids.
abstract: Local trauma to the lungs induces a temporary permeability disturbance with reduction in the osmotic reflection coefficient of a sheep lung lymph model. Proteolytic enzymes may be involved in this microvascular injury. In the present study, we tested the hypothesis that pretreatment with methylprednisolone prevents activation of proteolytic systems after pulmonary trauma and that these systems are of etiological importance in the development of the pulmonary lesion. Central markers of proteolytic cascade systems were monitored in sheep subjected to local trauma to the lungs (lung lymph fistula preparation) with (n = 7) or without (n = 7) methylprednisolone (30 mg/kg) pretreatment. In control animals, reduced levels of prothrombin, antithrombin, kallikrein inhibitors, antiplasmin, and increased level of plasminogen activator inhibitor (PAI) indicated systemic activation of the coagulation, kallikrein-kinin, and fibrinolytic systems. These changes, except for PAI, were more pronounced in lung lymph. High levels of thromboxane A2 and 6-keto prostaglandin F1 alpha were found in lymph. In steroid-pretreated animals, the prostanoid response was attenuated, but all other variables were similar to control animals; thus, steroids did not prevent either local or systemic proteolytic enzyme activation caused by local trauma to the lung. The etiological role of this activation in the development of lung lesion has not yet been evaluated.
authors.affiliation: Department of Anesthesia, University of Göteborg, Sweden.
authors.forename: S
authors.initials: S
authors.lastname: Andréasson
authors.forename: L
authors.initials: L
authors.lastname: Smith
authors.forename: A O
authors.initials: AO
authors.lastname: Aasen
authors.forename: E
authors.initials: E
authors.lastname: Eriksson
authors.forename: T
authors.initials: T
authors.lastname: Saldeen
authors.forename: B
authors.initials: B
authors.lastname: Risberg
mesh_terms: D000818:Animals; D004789:Enzyme Activation; D006023:Glycoproteins / Q000097:blood; D006439:Hemodynamics; D008168:Lung / Q000201:enzymology; D055370:Lung Injury; D008775:Methylprednisolone / Q000627:therapeutic use*; D010447:Peptide Hydrolases / Q000378:metabolism*; D010960:Plasminogen Activators / Q000037:antagonists & inhibitors; D015849:Plasminogen Inactivators; D012756:Sheep
chemical_list: D006023:Glycoproteins; D015849:Plasminogen Inactivators; D010447:Peptide Hydrolases; D010960:Plasminogen Activators; D008775:Methylprednisolone