title: Apocynin attenuates ventilator-induced lung injury in an isolated and perfused rat lung model.
abstract: BACKGROUND
  Apocynin suppresses the generation of reactive oxygen species (ROS) that are implicated in ventilator-induced lung injury (VILI). We thus hypothesized that apocynin attenuates VILI.
  
  
  METHODS
  VILI was induced by mechanical ventilation with tidal volume (V(t)) of 15 ml/kg in isolated and perfused rat lung. Apocynin was administered in the perfusate at onset of mechanical ventilation. A group ventilated with low V(t) of 5 ml/kg served as control. Hemodynamics, lung injury indices, inflammatory responses, and activation of apoptotic pathways were determined upon completion of mechanical ventilation.
  
  
  RESULTS
  There was an increase in lung permeability and lung weight gain after mechanical ventilation with high V(t), compared with low V (t). Levels of inflammatory cytokines including interleukin-1β (IL-1β), tumor necrosis factor-alpha (TNF-α), and macrophage inflammatory protein-2 (MIP-2) increased in lung lavage fluids; concentrations of carbonyl, thiobarbituric acid reactive substances, and H(2)O(2) were higher in perfusates and lung lavage fluids, and expression of myeloperoxidase, JNK, p38, and caspase-3 in lung tissue was greater in the high-V(t) than in the low-V(t) group. Administration of apocynin attenuated these inflammatory responses and lung permeability associated with decreased activation of nuclear factor-κB.
  
  
  CONCLUSIONS
  VILI is associated with inflammatory responses including generation of ROS, cytokines, and activation of mitogen-activated protein kinase cascades. Administration of apocynin at onset of mechanical ventilation attenuates inflammatory responses and VILI in the isolated, perfused rat lung model.
authors: Division of Pulmonary Immunology and Infectious Diseases, Chest Department, Taipei Veterans General Hospital, No. 201, Section 2, Shih-Pai Road, Taipei, Taiwan. chiang1990@gmail.com
authors: Chi-Huei
authors: CH
authors: Chiang
authors: Chiao-Hui
authors: CH
authors: Chuang
authors: Shiou-Ling
authors: SL
authors: Liu
authors: Tzong-Shyuan
authors: TS
authors: Lee
authors: Yu Ru
authors: YR
authors: Kou
authors: Haibo
authors: H
authors: Zhang
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