Effect of exogenous surfactant on the development of surfactant synthesis in premature rabbit lung.
Surfactant replacement is an effective therapy for neonatal respiratory distress syndrome. Full recovery from respiratory distress syndrome requires development of endogenous surfactant synthesis and metabolism. The influence of exogenous surfactant on the development of surfactant synthesis in premature lungs is not known. We hypothesized that different exogenous surfactants have different effects on the development of endogenous surfactant production in the premature lung. We treated organ cultures of d 25 fetal rabbit lung for 3 d with 100 mg/kg body weight of natural rabbit surfactant, Survanta, and Exosurf and measured their effects on the development of surfactant synthesis. Additional experiments tested how these surfactants and Curosurf affected surfactant protein (SP) SP-A, SP-B, and SP-C mRNA expression. Surfactant synthesis was measured as the incorporation of 3H-choline and 14C-glycerol into disaturated phosphatidylcholine recovered from lamellar bodies. Randomized-block ANOVA showed significant differences among treatments for incorporation of both labels (p < 0.01), with natural rabbit surfactant less than control, Survanta greater than control, and Exosurf unchanged. Additional experiments with natural rabbit surfactant alone showed no significant effects in doses up to 1000 mg/kg. Survanta stimulated disaturated phosphatidylcholine synthesis (173 +/- 41% of control; p = 0.01), increased total lamellar body disaturated phosphatidylcholine by 22% (p < 0.05), and increased 14C-disat-PC specific activity by 35% (p < 0.05). The response to Survanta was dose-dependent up to 1000 mg/kg. Survanta did not affect surfactant release. No surfactant altered the expression of mRNA for SP-A, SP-B, or SP-C. We conclude that surfactant replacement therapy can enhance the maturation of surfactant synthesis, but this potential benefit differs with different surfactant preparations.
Amato
Maurizio
M
Department of Medicine, University of Bern, Switzerland.
Petit
Kevin
K
Fiore
Humberto H
HH
Doyle
Cynthia A
CA
Frantz
Ivan D
ID
Nielsen
Heber C
HC
D000818:Animals; D001688:Biological Products; D002250:Carbon Radioisotopes; D002794:Choline / Q000493:pharmacokinetics; D004338:Drug Combinations; D005233:Fatty Alcohols / Q000494:pharmacology; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D005865:Gestational Age; D005990:Glycerol / Q000493:pharmacokinetics; D008168:Lung / Q000187:drug effects* / Q000196:embryology / Q000502:physiology*; D009924:Organ Culture Techniques; D010743:Phospholipids / Q000096:biosynthesis; D010767:Phosphorylcholine; D011092:Polyethylene Glycols / Q000494:pharmacology; D011247:Pregnancy; D037662:Pulmonary Surfactant-Associated Protein A / Q000235:genetics; D037701:Pulmonary Surfactant-Associated Protein B / Q000235:genetics; D037721:Pulmonary Surfactant-Associated Protein C / Q000235:genetics; D037661:Pulmonary Surfactant-Associated Proteins / Q000235:genetics*; D011663:Pulmonary Surfactants / Q000494:pharmacology*; D011817:Rabbits; D014316:Tritium
D001688:Biological Products; D002250:Carbon Radioisotopes; D004338:Drug Combinations; D005233:Fatty Alcohols; D010743:Phospholipids; D037662:Pulmonary Surfactant-Associated Protein A; D037701:Pulmonary Surfactant-Associated Protein B; D037721:Pulmonary Surfactant-Associated Protein C; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants; D014316:Tritium; D010767:Phosphorylcholine; D011092:Polyethylene Glycols; C047049:dipalmitoylphosphatidylcholine, hexadecanol, tyloxapol drug combination; D002794:Choline; D005990:Glycerol; C072197:beractant