Apocynin attenuates ventilator-induced lung injury in an isolated and perfused rat lung model

Abstract

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 2O 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. © 2011 Copyright jointly held by Springer and ESICM.