Intratracheal administration of DBcAMP attenuates edema formation in phosgene-induced acute lung injury

Alfred M. Sciuto, Paul Timothy Strickland, Thomas P. Kennedy, Yue Liang Guo, Gail H. Gurtner

Research output: Contribution to journalArticle

Abstract

Phosgene, a toxic gas widely used as an industrial chemical intermediate, is known to cause life-threatening latent noncardiogenic pulmonary edema. Mechanisms related to its toxicity appear to involve lipoxygenase mediators of arachidonic acid (AA) and can be inhibited by pretreatment with drugs that increase adenosine 3',5'-cyclic monophosphate (cAMP). In the present study, we used the isolated buffer-perfused rabbit lung model to investigate the mechanisms by which cAMP protects against phosgene-induced lung injury. Posttreatment with dibutyryl cAMP (DBcAMP) was given 60-85 min after exposure by an intravascular or intratracheal route. Lung weight gain (LWG) was measured continuously. AA metabolites leukotriene (LT) C4, LTD4, and LTE4 and 6-ketoprostaglandin F(1α) were measured in the perfusate at 70, 90, 110, 130, and 150 min after exposure. Tissue malondialdehyde and reduced and oxidized glutathione were analyzed 150 min postexposure. Compared with measurements in the lungs of rabbits exposed to phosgene alone, posttreatment with DBcAMP significantly reduced LWG, pulmonary arterial pressure, and inhibited the release of LTC4, LTD4, and LTE4. Intratracheal administration of DBcAMP was more effective than intravascular administration in reducing LWG. Posttreatment also decreased MDA and protected against glutathione oxidation observed with phosgene exposure. We conclude that phosgene causes marked glutathione oxidation, lipid peroxidation, release of AA mediators, and increases LWG. Posttreatment with DB-cAMP attenuates these effects, not only by previously described inhibition of pulmonary endothelial or epithelial cell contraction but also by inhibition of AA-mediator production and a novel antioxidant effect.

Original languageEnglish (US)
Pages (from-to)149-157
Number of pages9
JournalJournal of Applied Physiology
Volume80
Issue number1
StatePublished - Jan 1996
Externally publishedYes

Fingerprint

Phosgene
Acute Lung Injury
Edema
Lung
Weight Gain
Arachidonic Acid
Leukotriene E4
Glutathione
Leukotriene D4
Leukotriene C4
Arachidonate Lipoxygenases
Rabbits
Glutathione Disulfide
Poisons
Lung Injury
Pulmonary Edema
Malondialdehyde
Cyclic AMP
Lipid Peroxidation
Arterial Pressure

Keywords

  • arachidonic acid
  • dibutyryl adenosine 3',5'-cyclic monophosphate
  • glutathione
  • intravascular
  • leukotrienes
  • malondialdehyde
  • posttreatment
  • pulmonary edema
  • toxic gas

ASJC Scopus subject areas

  • Physiology
  • Endocrinology
  • Orthopedics and Sports Medicine
  • Physical Therapy, Sports Therapy and Rehabilitation

Cite this

Intratracheal administration of DBcAMP attenuates edema formation in phosgene-induced acute lung injury. / Sciuto, Alfred M.; Strickland, Paul Timothy; Kennedy, Thomas P.; Guo, Yue Liang; Gurtner, Gail H.

In: Journal of Applied Physiology, Vol. 80, No. 1, 01.1996, p. 149-157.

Research output: Contribution to journalArticle

Sciuto, Alfred M. ; Strickland, Paul Timothy ; Kennedy, Thomas P. ; Guo, Yue Liang ; Gurtner, Gail H. / Intratracheal administration of DBcAMP attenuates edema formation in phosgene-induced acute lung injury. In: Journal of Applied Physiology. 1996 ; Vol. 80, No. 1. pp. 149-157.
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