Postexposure treatment with aminophylline protects against phosgene- induced acute lung injury

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

Research output: Contribution to journalArticle

Abstract

Pretreatment with aminophylline has been shown to protect against various types of acute lung injury. Mechanisms responsible for protection are multifactorial but are thought to involve upregulation of cAMP. While previous studies focused on pretreatment, the present investigation examined post-treatment in rabbits following exposure to a lethal dose of the oxidant gas phosgene. Rabbits, 2-3 kg, were exposed to a cumulative dose of phosgene to attain a c x t exposure effect of 1500 ppm · min. Lungs were isolated in situ and perfused for 90-100 min after exposure with Krebs-Henseleit buffer at 40 mL/min. Pulmonary artery pressure (Ppa), tracheal pressure (Pt), and lung weight gain (lwg) were measured continuously. Leukotrienes C4/D4/E4 were measured in the perfusate every 20 min during perfusion. At the immediate conclusion of the experiment, lung tissue was frozen in liquid N2 and analyzed for reduced GSH, GSSG, cAMP, and lipid peroxidation (TBARS). Post-treatment with aminophylline 80-90 min after exposure significantly lowered Ppa, Pt, and lwg. Aminophylline significantly reduced TBARS and perfusate LTC4/D4/E4 and prevented phosgene-induced decreases in lung tissue cAMP. These data suggest that protective mechanisms observed with aminophylline involve decreased LTC4/D4/E4-mediated pulmonary capillary permeability and attenuated lipid peroxidation. Direct antipermeability effects of cAMP on cellular contraction may also be important in protection against phosgene-induced lung injury.

Original languageEnglish (US)
Pages (from-to)317-332
Number of pages16
JournalExperimental Lung Research
Volume23
Issue number4
StatePublished - 1997

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Phosgene
Aminophylline
Acute Lung Injury
Leukotriene C4
Lung
Tissue
Lipids
Pressure
Lipid Peroxidation
Weight Gain
Glutathione Disulfide
Oxidants
Rabbits
Leukotriene D4
Gases
Capillary Permeability
Lung Injury
Pulmonary Artery
Liquids
Up-Regulation

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

Cite this

Postexposure treatment with aminophylline protects against phosgene- induced acute lung injury. / Sciuto, Alfred M.; Strickland, Paul Timothy; Kennedy, Thomas P.; Gurtner, Gail H.

In: Experimental Lung Research, Vol. 23, No. 4, 1997, p. 317-332.

Research output: Contribution to journalArticle

Sciuto, Alfred M. ; Strickland, Paul Timothy ; Kennedy, Thomas P. ; Gurtner, Gail H. / Postexposure treatment with aminophylline protects against phosgene- induced acute lung injury. In: Experimental Lung Research. 1997 ; Vol. 23, No. 4. pp. 317-332.
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