Skip to main content
Mediators of Inflammation logoLink to Mediators of Inflammation
. 1997 Feb;6(1):39–45. doi: 10.1080/09629359791910

Lung eicosanoids in perinatal rats with congenital diaphragmatic hernia

H Ijsselstijn 1,2, F J Zijlstra 3, J P M Van Dijk 3, J C De Jongste 2, D Tibboel 1,✉
PMCID: PMC2365837  PMID: 18472832

Abstract

Abnormal levels of pulmonary eicosanoids have been reported in infants with persistent pulmonary hypertension (PPH) and congenital diaphragmatic hernia (CDH). We hypothesized that a dysbalance of vasoconstrictive and vasodilatory eicosanoids is involved in PPH in CDH patients. The levels of several eicosanoids in lung homogenates and in bronchoalveolar lavage fluid of controls and rats with CDH were measured after caesarean section or spontaneous birth. In controls the concentration of the stable metabolite of prostacyclin (6-keto-PGF1α), thromboxane A2 (TxB2), prostaglandin E2 (PGE2), and leukotriene B4 (LTB4) decreased after spontaneous birth. CDH pups showed respiratory insufficiency directly after birth. Their lungs had higher levels of 6- keto-PGF1α, reflecting the pulmonary vasodilator prostacyclin (PGI2), than those of controls. We conclude that in CDH abnormal lung eicosanoid levels are present perinatally. The elevated levels of 6-keto-PGF1α in CDH may reflect a compensation mechanism for increased vascular resistance.

Full Text

The Full Text of this article is available as a PDF (231.0 KB).

Selected References

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

  1. AGOSTONI E., TAGLIETTI A., AGOSTONI A. F., SETNIKAR I. Mechanical aspects of the first breath. J Appl Physiol. 1958 Nov;13(3):344–348. doi: 10.1152/jappl.1958.13.3.344. [DOI] [PubMed] [Google Scholar]
  2. Abman S. H., Shanley P. F., Accurso F. J. Failure of postnatal adaptation of the pulmonary circulation after chronic intrauterine pulmonary hypertension in fetal lambs. J Clin Invest. 1989 Jun;83(6):1849–1858. doi: 10.1172/JCI114091. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bindl L., Fahnenstich H., Peukert U. Aerosolised prostacyclin for pulmonary hypertension in neonates. Arch Dis Child Fetal Neonatal Ed. 1994 Nov;71(3):F214–F216. doi: 10.1136/fn.71.3.f214. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bos A. P., Tibboel D., Hazebroek F. W., Stijnen T., Molenaar J. C. Congenital diaphragmatic hernia: impact of prostanoids in the perioperative period. Arch Dis Child. 1990 Sep;65(9):994–995. doi: 10.1136/adc.65.9.994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bos A. P., Tibboel D., Koot V. C., Hazebroek F. W., Molenaar J. C. Persistent pulmonary hypertension in high-risk congenital diaphragmatic hernia patients: incidence and vasodilator therapy. J Pediatr Surg. 1993 Nov;28(11):1463–1465. doi: 10.1016/0022-3468(93)90431-j. [DOI] [PubMed] [Google Scholar]
  6. Brandsma A. E., Tibboel D., Vulto I. M., Egberts J., Ten Have-Opbroek A. A. Ultrastructural features of alveolar epithelial cells in the late fetal pulmonary acinus: a comparison between normal and hypoplastic lungs using a rat model of pulmonary hypoplasia and congenital diaphragmatic hernia. Microsc Res Tech. 1993 Dec 1;26(5):389–399. doi: 10.1002/jemt.1070260507. [DOI] [PubMed] [Google Scholar]
  7. Brandsma A. E., ten Have-Opbroek A. A., Vulto I. M., Molenaar J. C., Tibboel D. Alveolar epithelial composition and architecture of the late fetal pulmonary acinus: an immunocytochemical and morphometric study in a rat model of pulmonary hypoplasia and congenital diaphragmatic hernia. Exp Lung Res. 1994 Nov-Dec;20(6):491–515. doi: 10.3109/01902149409031734. [DOI] [PubMed] [Google Scholar]
  8. Bui K. C., Hammerman C., Hirschl R. B., Hill V., Snedecor S. M., Schumacher R., Bartlett R. H. Plasma prostanoids in neonates with pulmonary hypertension treated with conventional therapy and with extracorporeal membrane oxygenation. J Thorac Cardiovasc Surg. 1991 Jun;101(6):973–983. [PubMed] [Google Scholar]
  9. Cassin S. Role of prostaglandins, thromboxanes, and leukotrienes in the control of the pulmonary circulation in the fetus and newborn. Semin Perinatol. 1987 Jan;11(1):53–63. [PubMed] [Google Scholar]
  10. Cassin S. The role of eicosanoids and endothelium-dependent factors in regulation of the fetal pulmonary circulation. J Lipid Mediat. 1993 Mar-Apr;6(1-3):477–485. [PubMed] [Google Scholar]
  11. Clyman R. I., Mauray F., Roman C., Rudolph A. M., Heymann M. A. Circulating prostaglandin E2 concentrations and patent ductus arteriosus in fetal and neonatal lambs. J Pediatr. 1980 Sep;97(3):455–461. doi: 10.1016/s0022-3476(80)80205-8. [DOI] [PubMed] [Google Scholar]
  12. Coceani F., Olley P. M. Eicosanoids in the fetal and transitional pulmonary circulation. Chest. 1988 Mar;93(3 Suppl):112S–117S. doi: 10.1378/chest.93.3_supplement.112s. [DOI] [PubMed] [Google Scholar]
  13. Dobyns E. L., Wescott J. Y., Kennaugh J. M., Ross M. N., Stenmark K. R. Eicosanoids decrease with successful extracorporeal membrane oxygenation therapy in neonatal pulmonary hypertension. Am J Respir Crit Care Med. 1994 Apr;149(4 Pt 1):873–880. doi: 10.1164/ajrccm.149.4.8143049. [DOI] [PubMed] [Google Scholar]
  14. Ford W. D., James M. J., Walsh J. A. Congenital diaphragmatic hernia: association between pulmonary vascular resistance and plasma thromboxane concentrations. Arch Dis Child. 1984 Feb;59(2):143–146. doi: 10.1136/adc.59.2.143. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. George D. K., Cooney T. P., Chiu B. K., Thurlbeck W. M. Hypoplasia and immaturity of the terminal lung unit (acinus) in congenital diaphragmatic hernia. Am Rev Respir Dis. 1987 Oct;136(4):947–950. doi: 10.1164/ajrccm/136.4.947. [DOI] [PubMed] [Google Scholar]
  16. Hammerman C., Lass N., Strates E., Komar K., Bui K. C. Prostanoids in neonates with persistent pulmonary hypertension. J Pediatr. 1987 Mar;110(3):470–472. doi: 10.1016/s0022-3476(87)80520-6. [DOI] [PubMed] [Google Scholar]
  17. Kluth D., Kangah R., Reich P., Tenbrinck R., Tibboel D., Lambrecht W. Nitrofen-induced diaphragmatic hernias in rats: an animal model. J Pediatr Surg. 1990 Aug;25(8):850–854. doi: 10.1016/0022-3468(90)90190-k. [DOI] [PubMed] [Google Scholar]
  18. Leffler C. W., Hessler J. R., Green R. S. Mechanism of stimulation of pulmonary prostacyclin synthesis at birth. Prostaglandins. 1984 Dec;28(6):877–887. doi: 10.1016/0090-6980(84)90041-8. [DOI] [PubMed] [Google Scholar]
  19. Leffler C. W., Hessler J. R., Green R. S. The onset of breathing at birth stimulates pulmonary vascular prostacyclin synthesis. Pediatr Res. 1984 Oct;18(10):938–942. doi: 10.1203/00006450-198410000-00006. [DOI] [PubMed] [Google Scholar]
  20. Leffler C. W., Tyler T. L., Cassin S. Effect of indomethacin on pulmonary vascular response to ventilation of fetal goats. Am J Physiol. 1978 Apr;234(4):H346–H351. doi: 10.1152/ajpheart.1978.234.4.H346. [DOI] [PubMed] [Google Scholar]
  21. Mitchell M. D. Prostaglandins during pregnancy and the perinatal period. J Reprod Fertil. 1981 May;62(1):305–315. doi: 10.1530/jrf.0.0620305. [DOI] [PubMed] [Google Scholar]
  22. Molenaar J. C., Bos A. P., Hazebroek F. W., Tibboel D. Congenital diaphragmatic hernia, what defect? J Pediatr Surg. 1991 Mar;26(3):248–254. doi: 10.1016/0022-3468(91)90497-h. [DOI] [PubMed] [Google Scholar]
  23. Moncada S., Vane J. R. Pharmacology and endogenous roles of prostaglandin endoperoxides, thromboxane A2, and prostacyclin. Pharmacol Rev. 1978 Sep;30(3):293–331. [PubMed] [Google Scholar]
  24. Nakayama D. K., Motoyama E. K., Evans R., Hannakan C. Relation between arterial hypoxemia and plasma eicosanoids in neonates with congenital diaphragmatic hernia. J Surg Res. 1992 Dec;53(6):615–620. doi: 10.1016/0022-4804(92)90263-y. [DOI] [PubMed] [Google Scholar]
  25. Steinhorn R. H., Millard S. L., Morin F. C., 3rd Persistent pulmonary hypertension of the newborn. Role of nitric oxide and endothelin in pathophysiology and treatment. Clin Perinatol. 1995 Jun;22(2):405–428. [PubMed] [Google Scholar]
  26. Stenmark K. R., James S. L., Voelkel N. F., Toews W. H., Reeves J. T., Murphy R. C. Leukotriene C4 and D4 in neonates with hypoxemia and pulmonary hypertension. N Engl J Med. 1983 Jul 14;309(2):77–80. doi: 10.1056/NEJM198307143090204. [DOI] [PubMed] [Google Scholar]
  27. Stolar C. J., Dillon P. W., Stalcup S. A. Extracorporeal membrane oxygenation and congenital diaphragmatic hernia: modification of the pulmonary vasoactive profile. J Pediatr Surg. 1985 Dec;20(6):681–683. doi: 10.1016/s0022-3468(85)80023-3. [DOI] [PubMed] [Google Scholar]
  28. Tenbrinck R., Gaillard J. L., Tibboel D., Kluth D., Lachmann B., Molenaar J. C. Pulmonary vascular abnormalities in experimentally induced congenital diaphragmatic hernia in rats. J Pediatr Surg. 1992 Jul;27(7):862–865. doi: 10.1016/0022-3468(92)90385-k. [DOI] [PubMed] [Google Scholar]
  29. Weir E. K., McMurtry I. F., Tucker A., Reeves J. T., Grover R. F. Prostaglandin synthetase inhibitors do not decrease hypoxic pulmonary vasoconstriction. J Appl Physiol. 1976 Nov;41(5 Pt 1):714–718. doi: 10.1152/jappl.1976.41.5.714. [DOI] [PubMed] [Google Scholar]
  30. Zijlstra F. J., Vincent J. E., Mol W. M., Hoogsteden H. C., Van Hal P. T., Jongejan R. C. Eicosanoid levels in bronchoalveolar lavage fluid of young female smokers and non-smokers. Eur J Clin Invest. 1992 May;22(5):301–306. doi: 10.1111/j.1365-2362.1992.tb01466.x. [DOI] [PubMed] [Google Scholar]

Articles from Mediators of Inflammation are provided here courtesy of Wiley

RESOURCES