The differential synergistic injurious effect of resistive breathing on pulmonary and extra-pulmonary lung injury

Abstract

<b>Introduction:</b> Resistive breathing (RB) is characterized by increased mechanical stress in the lung. Our group has shown that RB induces lung injury in healthy animals. Whether RB exerts additional injurious effects when added to direct pulmonary or extrapulmonary lung injury from gram negative bacteria is unknown. We aimed to investigate the synergistic effect of RB on LPS-induced lung injury. <b>Methods:</b> C57BL/6 mice were either exposed to LPS aerosol (10mg/3ml) (pulmonary) or received an intraperitoneal injection of LPS (10 mg/kg) (extrapulmonary lung injury). Mice were then anaesthetized, the trachea was exposed and a nylon band was sutured around it, to reduce surface area by half. RB through tracheal banding was applied for 24 hours. Respiratory system mechanics were measured, BAL was performed and lung sections were evaluated for histological features of lung injury. <b>Results:</b> LPS inhalation increased BAL cellularity, mainly neutrophils (p&lt;0.001), total protein levels (p&lt;0.001), TNF and IL-6 in BAL (p&lt;0.001) and increased lung injury score. Lung mechanics were not altered. Adding RB to inhaled LPS further increased BAL cellularity, total protein count, TNF and lung injury score. Intraperitoneal LPS increased BAL cellularity, mainly macrophages, total protein levels, decreased static compliance (p=0.004) and increased lung injury score. Adding RB further increased histological features of lung injury, mainly capillary congestion and interstitial leukocyte infiltration. <b>Conclusions:</b> Resistive breathing exerts synergistic injurious effects when combined with inhalational LPS-induced lung injury, while the additive effect on extrapulmonary lung injury is less prominent.