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
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.