Dexamethasone enhances the activity of rSP-C surfactant but not of exosurf in a rat model of the acute lung injury.
The possible enhancement of surfactant activity by pretreatment with a glucocorticosteroid (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 phospholipids containing surfactant, Wellcome GmbH, Burgwedel, Germany) and a rSP-C based surfactant, respectively. Both surfactants were intratracheally instilled at doses of 25 and 100 mg phospholipids per kg body weight and were compared with pretreatment with dexamethasone at each dose level. These groups were also compared with untreated controls and to pretreatment with dexamethasone alone with respect to improvements in oxygenation, to inhibition of infiltration of polymorphonuclear neutrophil leukocytes (PMNL) and to influence formation of hyaline membranes. Dexamethasone alone had no influence on the reduced PaO(2) but reduced the infiltration of PMNL and the formation of hyaline membranes. Dexamethasone improved the oxygenation at both doses of rSP-C surfactant. At the low dose of rSP-C surfactant there were additional effects detectable with regard to histopathologic improvements. In contrast, dexamethasone had no additional effect on oxygenation and formation 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 alone. In this animal model, pretreatment with dexamethasone showed additional effects on rSP-C surfactant that were superior to each treatment alone. From the comparison of rSP-C surfactant with the synthetic surfactant preparation Exosurf, we conclude that the activity of Exosurf cannot be improved substantially by additional pretreatment with drugs like glucocorticosteroids.
Häfner
D
D
Department of Respiratory Pharmacology, Institute of Pathology and Toxicology, Byk Gulden, Post-box 100310, D-78403, Konstanz, Germany. dietrich.haefner@byk.de
Germann
P G
PG
D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D003907:Dexamethasone / Q000627:therapeutic use*; D004338:Drug Combinations; D004357:Drug Synergism; D005233:Fatty Alcohols / Q000627:therapeutic use*; D008168:Lung / Q000187:drug effects / Q000473:pathology; D008297:Male; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology; D010100:Oxygen / Q000097:blood; D010767:Phosphorylcholine; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D011175:Positive-Pressure Respiration; D011510:Proteolipids / Q000627:therapeutic use*; D011663:Pulmonary Surfactants / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000627:therapeutic use; D012128:Respiratory Distress Syndrome / Q000188:drug therapy*
D004338:Drug Combinations; D005233:Fatty Alcohols; D011510:Proteolipids; D011663:Pulmonary Surfactants; D011994:Recombinant Proteins; D010767:Phosphorylcholine; D011092:Polyethylene Glycols; D003907:Dexamethasone; C047049:dipalmitoylphosphatidylcholine, hexadecanol, tyloxapol drug combination; D010100:Oxygen