Time profile of oxidative stress and neutrophil activation in ovine acute lung injury and sepsis

Matthias Lange, Csaba Szabo, Daniel L. Traber, Eszter Horvath, Atsumori Hamahata, Yoshimitsu Nakano, Lillian D. Traber, Robert A. Cox, Frank C. Schmalstieg, David N. Herndon, Perenlei Enkhbaatar

Research output: Contribution to journalArticlepeer-review

29 Scopus citations


The formation of oxidative stress in the lung and activation of neutrophils are major determinants in the development of respiratory failure after acute lung injury and sepsis. However, the time changes of these pathogenic factors have not been sufficiently described. Twenty-four chronically instrumented sheep were subjected to cotton smoke inhalation injury and instillation of live Pseudomonas aeruginosa into both lungs. The sheep were euthanized at 4, 8, 12, 18, and 24 h after injury. Additional sheep received sham injury and were euthanized after 24 h. Pulmonary function was assessed by determination of oxygenation index and pulmonary shunt fraction. In addition, lung tissue was harvested at the respective time points for the measurement of malondialdehyde, interleukin 6, poly(ADP ribose), myeloperoxidase, and alveolar polymorphonuclear neutrophil score. The injury induced severe respiratory failure that was associated with an early increase in lipid peroxidation and interleukin 6 expression. The injury further led to an increase in poly(ADP ribose) activity that reached its peak at 12 h after injury and declined afterward. In addition, progressive increases in markers of neutrophil accumulation in the lung were observed. The peak of neutrophil accumulation in the lung was associated with a severe depletion of circulating neutrophils. The results from our model may enhance the understanding of the pathophysiological alterations after acute lung injury and sepsis and thus be useful in exploring therapeutic interventions directed at modifying the expression or activation of inflammatory mediators.

Original languageEnglish (US)
Pages (from-to)468-472
Number of pages5
Issue number5
StatePublished - May 2012


  • Lipid peroxidation
  • Malondialdehyde
  • Sheep
  • Smoke inhalation

ASJC Scopus subject areas

  • Emergency Medicine
  • Critical Care and Intensive Care Medicine


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