Mechanisms associated with progression from lobar inflammation to bilateral lung injury: an experimental study.

BACKGROUND: Localized lung insult, such as pneumonia, can increase respiratory drive and effort. The interplay between the initial injury, the inflammatory reaction and increased drive and effort could damage other areas and progress to bilateral lung injury. METHODS: Localized pulmonary inflammation was induced through instillation of 0.5 mg/kg lipopolysaccharide (LPS) in the left lower lobe of 18 pigs, while 5 animals served as sham controls. After 24 hours of spontaneous breathing, the severity of right lung injury was assessed by the validated histological score and correlated with potential physiological and biological determinants. RESULTS: Animals challenged with lobar inflammation developed bilateral lung injury, associated with increased respiratory drive and effort. Histological score of the right lung was characterized by wide inter-individual variability (median 11 [8-14], range 3-25). Right lung injury score was correlated with respiratory drive and effort; with respiratory rate and minute ventilation, but not with tidal volume; with peak inspiratory and driving transpulmonary pressures, and with EIT-derived lung strain; with lower sub-atmospheric alveolar pressure and with more negative end-expiratory transpulmonary pressure. Right lung injury score was also correlated with inflammatory plasma cytokines: higher SDF-1α and lower IL-1Ra, IL-5 and GM-CSF. CONCLUSIONS: An experimental model of localized lung inflammation allowed us to investigate the role of specific pathophysiological mechanisms for the development of injury in previously healthy lung regions.