title: Time profile of oxidative stress and neutrophil activation in ovine acute lung injury and sepsis.
abstract: 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.
authors.affiliation: Investigational Intensive Care Unit, Department of Anesthesiology, University of Texas Medical Branch, Galveston, Texas 77550, USA. lanm@gmx.de
authors.forename: Matthias
authors.initials: M
authors.lastname: Lange
authors.forename: Csaba
authors.initials: C
authors.lastname: Szabo
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Traber
authors.forename: Eszter
authors.initials: E
authors.lastname: Horvath
authors.forename: Atsumori
authors.initials: A
authors.lastname: Hamahata
authors.forename: Yoshimitsu
authors.initials: Y
authors.lastname: Nakano
authors.forename: Lillian D
authors.initials: LD
authors.lastname: Traber
authors.forename: Robert A
authors.initials: RA
authors.lastname: Cox
authors.forename: Frank C
authors.initials: FC
authors.lastname: Schmalstieg
authors.forename: David N
authors.initials: DN
authors.lastname: Herndon
authors.forename: Perenlei
authors.initials: P
authors.lastname: Enkhbaatar
mesh_terms: D055371:Acute Lung Injury / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000276:immunology; D018836:Inflammation Mediators / Q000276:immunology / Q000378:metabolism; D015850:Interleukin-6 / Q000276:immunology / Q000378:metabolism; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008315:Malondialdehyde / Q000276:immunology / Q000378:metabolism; D018375:Neutrophil Activation / Q000276:immunology*; D009504:Neutrophils / Q000276:immunology* / Q000378:metabolism; D018384:Oxidative Stress / Q000276:immunology*; D009195:Peroxidase / Q000276:immunology / Q000378:metabolism; D011064:Poly Adenosine Diphosphate Ribose / Q000276:immunology / Q000378:metabolism; D011552:Pseudomonas Infections / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D011550:Pseudomonas aeruginosa; D012756:Sheep; D015208:Smoke Inhalation Injury / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D013997:Time Factors
chemical_list: D018836:Inflammation Mediators; D015850:Interleukin-6; D011064:Poly Adenosine Diphosphate Ribose; D008315:Malondialdehyde; D009195:Peroxidase