Alveolar Tidal Flooding - a New Mechanism of Ventilator-Induced Lung Injury?

While mechanical ventilation is a mainstay of therapy for the ARDS, it can simultaneously trigger ventilator induced lung injury (VILI). Optimization of ventilation strategies, necessitate a better understanding of alveolar dynamics and the mechanisms of alveolar injury in the mechanically ventilated and edematous lung. To this end, we visualized alveolar dynamics directly in a murine model of alveolar edema by intravital microscopy.Alveolar edema was modeled in anesthetized male C57BL/6 mice by PBS instillation (13 mL/kg BW) into the right lung. The fluid-instilled right lung was directly imaged via a thoracic window by darkfield intravital microscopy. Alveolar dynamics were continuously monitored during stepwise changes of ventilator settings.Mechanical ventilation of fluid-instilled lungs induced cyclic fluid motion, a phenomenon that we termed "alveolar tidal flooding" (ATF). ATF resulted not in structural, but functional cyclic collapse and re-opening of alveoli. Cyclic shifts of air-liquid interfaces exerted deleterious shear stresses along the alveolar epithelium, which could be replicated in a microfluidic system resulting in epithelial cell detachment. Increased shear stress caused cholesterol release into the bronchoalveolar lavage fluid signifying disintegration of the epithelial plasma membrane. ATF of edematous alveoli increased in an IPP-dependent manner with an onset threshold of IPP=20 cmH2O under ZEEP. Conversely, ATF was largely prevented at IPP values of 30...
Source: European Respiratory Journal - Category: Respiratory Medicine Authors: Tags: Mechanisms of Lung Injury and Repair Source Type: research