Distribution and mechanisms of lung injury induced by spontaneous breathing in experimental acute respiratory distress syndrome: A comprehensive investigation towards improvement of protective mechanical ventilation

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Spontaneous breathing during mechanical ventilation in patients with the acute respiratory distress syndrome (ARDS) can affect lung injury. In a previous project, we showed that in moderate ARDS, spontaneous breathing decreases global stress and strain in the lungs, contributing to improve gas exchange and reduce lung injury. In contrast, others and we observed that in severe ARDS, spontaneous breathing has been suggested to worsen lung function and damage, but the mechanisms underlying such effects are only poorly understood. In this continuation project, we aim at investigating how stress-and-strain vs. time product and slope modulate the mechano-sensitive response of amphiregulin and inflammatory mediators in alveolar epithelial cells. Also, we shall investigate the effects of spontaneous breathing on intrapleural pressure and regional distribution of inflammation in an experimental model of severe ARDS with stable and unstable lung units at end-expiration. We hypothesize that, during mechanical ventilation in severe ARDS, the effects of spontaneous breathing on lung function and injury are determined by the stress-and-strain vs. time product and slope of alveolar epithelial cells, as well as the stability of lung units at end-expiration. This investigation may contribute to the improvement of lung protective ventilation strategies in ARDS.