Skip to main content
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1987 May;79(5):1371–1378. doi: 10.1172/JCI112964

Corticosteroids and surfactant change lung function and protein leaks in the lungs of ventilated premature rabbits.

M Ikegami, D Berry, T elKady, A Pettenazzo, S Seidner, A Jobe
PMCID: PMC424392  PMID: 3571492

Abstract

Fetal rabbits were treated with corticosteroids by maternal administration for 48 h before delivery at 27 d gestational age. The treated and control rabbits were placed on ventilator-plethysmographs so that ventilation could be adjusted by regulation of tidal volumes to 10-13 ml/kg body wt. [125I]albumin was mixed with fetal lung fluid at birth, alternate rabbits from each litter were treated with Surfactant-TA, and [131I]albumin was injected intravascularly. The movement of the labeled albumins into and out of the alveolar wash and lung tissue was measured after 30 min of ventilation. Corticosteroid treatment (total dose, 0.2 mg/kg betamethasone) significantly decreased the protein leak across the endothelium (P less than 0.001) but increased the protein leak across the epithelium (P less than 0.001). Surfactant treatment decreased both the endothelial and epithelial leaks, and the combination of surfactant and corticosteroid treatments decreased endothelial leaks to 29% of control values and increased compliance more than either treatment alone. The 48-h corticosteroid treatment did not increase alveolar surfactant pool sizes. Corticosteroids significantly changed lung protein leaks independently of surfactant, and improved the response of the preterm lung to surfactant treatments.

Full text

PDF
1375

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. AVERY M. E., MEAD J. Surface properties in relation to atelectasis and hyaline membrane disease. AMA J Dis Child. 1959 May;97(5 Pt 1):517–523. doi: 10.1001/archpedi.1959.02070010519001. [DOI] [PubMed] [Google Scholar]
  2. BARTLETT G. R. Phosphorus assay in column chromatography. J Biol Chem. 1959 Mar;234(3):466–468. [PubMed] [Google Scholar]
  3. BLIGH E. G., DYER W. J. A rapid method of total lipid extraction and purification. Can J Biochem Physiol. 1959 Aug;37(8):911–917. doi: 10.1139/o59-099. [DOI] [PubMed] [Google Scholar]
  4. Bauer C. R., Morrison J. C., Poole W. K., Korones S. B., Boehm J. J., Rigatto H., Zachman R. D. A decreased incidence of necrotizing enterocolitis after prenatal glucocorticoid therapy. Pediatrics. 1984 May;73(5):682–688. [PubMed] [Google Scholar]
  5. Bland R. D., Hansen T. N., Haberkern C. M., Bressack M. A., Hazinski T. A., Raj J. U., Goldberg R. B. Lung fluid balance in lambs before and after birth. J Appl Physiol Respir Environ Exerc Physiol. 1982 Oct;53(4):992–1004. doi: 10.1152/jappl.1982.53.4.992. [DOI] [PubMed] [Google Scholar]
  6. Bunton T. E., Plopper C. G. Triamcinolone-induced structural alterations in the development of the lung of the fetal rhesus macaque. Am J Obstet Gynecol. 1984 Jan 15;148(2):203–215. doi: 10.1016/s0002-9378(84)80177-5. [DOI] [PubMed] [Google Scholar]
  7. Doyle L. W., Kitchen W. H., Ford G. W., Rickards A. L., Lissenden J. V., Ryan M. M. Effects of antenatal steroid therapy on mortality and morbidity in very low birth weight infants. J Pediatr. 1986 Feb;108(2):287–292. doi: 10.1016/s0022-3476(86)81006-x. [DOI] [PubMed] [Google Scholar]
  8. Egan E. A., Olver R. E., Strang L. B. Changes in non-electrolyte permeability of alveoli and the absorption of lung liquid at the start of breathing in the lamb. J Physiol. 1975 Jan;244(1):161–179. doi: 10.1113/jphysiol.1975.sp010789. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Ekelund L., Enhorning G. Glucocorticoids and beta-adrenergic-receptor agonists: their combined effect on fetal rabbit lung surfactant. Am J Obstet Gynecol. 1985 Aug 15;152(8):1063–1067. doi: 10.1016/0002-9378(85)90563-0. [DOI] [PubMed] [Google Scholar]
  10. Freese W. B., Hallman M. The effect of betamethasone and fetal sex on the synthesis and maturation of lung surfactant phospholipids in rabbits. Biochim Biophys Acta. 1983 Jan 7;750(1):47–59. doi: 10.1016/0005-2760(83)90203-5. [DOI] [PubMed] [Google Scholar]
  11. Hemberger J. A., Schanker L. S. Effect of cortisone on permeability of the neonatal rat lung to drugs. Biol Neonate. 1981;40(1-2):99–104. doi: 10.1159/000241477. [DOI] [PubMed] [Google Scholar]
  12. Ikegami M., Jobe A., Berry D. A protein that inhibits surfactant in respiratory distress syndrome. Biol Neonate. 1986;50(3):121–129. doi: 10.1159/000242588. [DOI] [PubMed] [Google Scholar]
  13. Jobe A., Ikegami M., Jacobs H., Jones S., Conaway D. Permeability of premature lamb lungs to protein and the effect of surfactant on that permeability. J Appl Physiol Respir Environ Exerc Physiol. 1983 Jul;55(1 Pt 1):169–176. doi: 10.1152/jappl.1983.55.1.169. [DOI] [PubMed] [Google Scholar]
  14. Jobe A., Jacobs H., Ikegami M., Berry D. Lung protein leaks in ventilated lambs: effects of gestational age. J Appl Physiol (1985) 1985 Apr;58(4):1246–1251. doi: 10.1152/jappl.1985.58.4.1246. [DOI] [PubMed] [Google Scholar]
  15. Kessler D. L., Truog W. E., Murphy J. H., Palmer S., Standaert T. A., Woodrum D. E., Hodson W. A. Experimental hyaline membrane disease in the premature monkey: effects of antenatal dexamethasone. Am Rev Respir Dis. 1982 Jul;126(1):62–69. doi: 10.1164/arrd.1982.126.1.62. [DOI] [PubMed] [Google Scholar]
  16. Kikkawa Y., Kaibara M., Motoyama E. K., Orzalesi M. M., Cook C. D. Morphologic development of fetal rabbit lung and its acceleration with cortisol. Am J Pathol. 1971 Aug;64(2):423–442. [PMC free article] [PubMed] [Google Scholar]
  17. Kotas R. V., Avery M. E. Accelerated appearance of pulmonary surfactant in the fetal rabbit. J Appl Physiol. 1971 Mar;30(3):358–361. doi: 10.1152/jappl.1971.30.3.358. [DOI] [PubMed] [Google Scholar]
  18. Lachmann B., Grossman G., Nilsson R., Robertson B. Effect of supplementary surfactant on in vivo lung mechanics in the premature rabbit neonate. Eur J Pediatr. 1981 May;136(2):173–179. doi: 10.1007/BF00441920. [DOI] [PubMed] [Google Scholar]
  19. Lachmann B., Grossmann G., Freyse J., Robertson B. Lung-thorax compliance in the artificially ventilated premature rabbit neonate in relation to variations in inspiration:expiration ratio. Pediatr Res. 1981 May;15(5):833–838. [PubMed] [Google Scholar]
  20. Liggins G. C., Howie R. N. A controlled trial of antepartum glucocorticoid treatment for prevention of the respiratory distress syndrome in premature infants. Pediatrics. 1972 Oct;50(4):515–525. [PubMed] [Google Scholar]
  21. Liggins G. C. Premature delivery of foetal lambs infused with glucocorticoids. J Endocrinol. 1969 Dec;45(4):515–523. doi: 10.1677/joe.0.0450515. [DOI] [PubMed] [Google Scholar]
  22. Maniscalco W. M., Finkelstein J. N., Parkhurst A. B. Dexamethasone increases de novo fatty acid synthesis in fetal rabbit lung explants. Pediatr Res. 1985 Dec;19(12):1272–1277. doi: 10.1203/00006450-198512000-00010. [DOI] [PubMed] [Google Scholar]
  23. Mason R. J., Nellenbogen J., Clements J. A. Isolation of disaturated phosphatidylcholine with osmium tetroxide. J Lipid Res. 1976 May;17(3):281–284. [PubMed] [Google Scholar]
  24. Mendelson C. R., Snyder J. M. Effect of cortisol on the synthesis of lamellar body glycerophospholipids in fetal rabbit lung tissue in vitro. Biochim Biophys Acta. 1985 Mar 27;834(1):85–94. doi: 10.1016/0005-2760(85)90179-1. [DOI] [PubMed] [Google Scholar]
  25. Mitzner W., Johnson J. W., Beck J., London W., Sly D. Influence of betamethasone on the development of mechanical properties in the fetal rhesus monkey lung. Am Rev Respir Dis. 1982 Feb;125(2):233–238. doi: 10.1164/arrd.1982.125.2.233. [DOI] [PubMed] [Google Scholar]
  26. Mitzner W., Johnson J. W., Scott R., London W. T., Palmer A. E. Effect of betamethasone on pressure-volume relationship of fetal rhesus monkey lung. J Appl Physiol Respir Environ Exerc Physiol. 1979 Aug;47(2):377–382. doi: 10.1152/jappl.1979.47.2.377. [DOI] [PubMed] [Google Scholar]
  27. Nilsson R., Grossmann G., Robertson B. Bronchiolar epithelial lesions induced in the premature rabbit neonate by short periods of artificial ventilation. Acta Pathol Microbiol Scand A. 1980 Nov;88(6):359–367. doi: 10.1111/j.1699-0463.1980.tb02507.x. [DOI] [PubMed] [Google Scholar]
  28. Platzker A. C., Kitterman J. A., Mescher E. J., Clements J. A., Tooley W. H. Surfactant in the lung and tracheal fluid of the fetal lamb and acceleration of its appearance by dexamethasone. Pediatrics. 1975 Oct;56(4):554–561. [PubMed] [Google Scholar]
  29. Robertson B., Berry D., Curstedt T., Grossmann G., Ikegami M., Jacobs H., Jobe A., Jones S. Leakage of protein in the immature rabbit lung; effect of surfactant replacement. Respir Physiol. 1985 Sep;61(3):265–276. doi: 10.1016/0034-5687(85)90070-2. [DOI] [PubMed] [Google Scholar]
  30. Rooney S. A., Gobran L. I., Marino P. A., Maniscalco W. M., Gross I. Effects of betamethasone on phospholipid content, composition and biosynthesis in the fetal rabbit lung. Biochim Biophys Acta. 1979 Jan 29;572(1):64–76. doi: 10.1016/0005-2760(79)90200-5. [DOI] [PubMed] [Google Scholar]
  31. Rooney S. A. The surfactant system and lung phospholipid biochemistry. Am Rev Respir Dis. 1985 Mar;131(3):439–460. doi: 10.1164/arrd.1985.131.3.439. [DOI] [PubMed] [Google Scholar]
  32. Solimano A., Bryan C., Jobe A., Ikegami M., Jacobs H. Effects of high-frequency and conventional ventilation on the premature lamb lung. J Appl Physiol (1985) 1985 Nov;59(5):1571–1577. doi: 10.1152/jappl.1985.59.5.1571. [DOI] [PubMed] [Google Scholar]
  33. Stonestreet B. S., Hansen N. B., Laptook A. R., Oh W. Glucocorticoid accelerates renal functional maturation in fetal lambs. Early Hum Dev. 1983 Oct;8(3-4):331–341. doi: 10.1016/0378-3782(83)90016-6. [DOI] [PubMed] [Google Scholar]
  34. Wang N. S., Kotas R. V., Avery M. E., Thurlbeck W. M. Accelerated appearance of osmiophilic bodies in fetal lungs following steroid injection. J Appl Physiol. 1971 Mar;30(3):362–365. doi: 10.1152/jappl.1971.30.3.362. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES