Dexamethasone enhances the activity of rSP-C surfactant but not of Exosurfin a rat model of the acute lung injury

Citation
D. Hafner et Pg. Germann, Dexamethasone enhances the activity of rSP-C surfactant but not of Exosurfin a rat model of the acute lung injury, J PHARM TOX, 42(1), 1999, pp. 39-48
Citations number
21
Categorie Soggetti
Pharmacology & Toxicology
Journal title
JOURNAL OF PHARMACOLOGICAL AND TOXICOLOGICAL METHODS
ISSN journal
10568719 → ACNP
Volume
42
Issue
1
Year of publication
1999
Pages
39 - 48
Database
ISI
SICI code
1056-8719(199909)42:1<39:DETAOR>2.0.ZU;2-8
Abstract
The possible enhancement of surfactant activity by pretreatment with a gluc ocorticosteroid (dexamethasone) was investigated in a rat lung lavage model of acute lung injury. Animals received a dose of dexamethasone (10 mg/kg i .p.) prior to the protein-free surfactant preparation Exosurf (pure phospho lipids containing surfactant, Wellcome GmbH, Burgwedel, Germany) and a rSP- C based surfactant, respectively. Both surfactants were intratracheally ins tilled at doses of 25 and 100 mg phospholipids per kg body weight and were com pared with pretreatment with dexamethasone at each dose level. These gr oups were also compared with untreated controls and to pr-e treatment with dexamethasone alone with respect to improvements in oxygenation, to inhibit ion of infiltration of polymorphonuclear neutrophil leukocytes (PMNL) and t o influence formation of hyaline membranes. Dexamethasone alone had no infl uence on the reduced PaO2 but reduced the infiltration of PMNL and the form ation of hyaline membranes. Dexamethasone improved the oxygenation at both doses of rSP-C surfactant. At the low dose of rSP-C surfactant there were a dditional effects detectable with regard to histopathologic improvements. I n contrast, dexamethasone had no additional effect on oxygenation and forma tion of hyaline membranes when combined with Exosurf. Only the infiltration of PMNL was decreased by combined treatment with dexamethasone and Exosurf . The effect was comparable to that of pretreatment with dexamethasone alon e. In this animal model, pretreatment with dexamethasone showed additional effects on rSP-C surfactant that were superior to each treatment alone. Fro m the comparison of rSP-C surfactant with the synthetic surfactant preparat ion Exosurf, we conclude that the activity of Exosurf cannot be improved su bstantially by additional pretreatment with drugs like glucocorticosteroids . (C) 2000 Elsevier Science Inc. All rights reserved.