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Updated: Jun 1, 2026
Method of Isolated Ex Vivo Lung Perfusion in a Rat Model: Lessons Learned from Developing a Rat EVLP Program
Published on: February 25, 2015
Apocynin attenuates ventilator-induced lung injury in an isolated and perfused rat lung model
Chi-Huei Chiang1, Chiao-Hui Chuang, Shiou-Ling Liu
1Division of Pulmonary Immunology and Infectious Diseases, Chest Department, Taipei Veterans General Hospital, No. 201, Section 2, Shih-Pai Road, Taipei, Taiwan. chiang1990@gmail.com
Rationale:
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.
