Abstract
Mechanical ventilation is vital to the management of acute respiratory distress syndrome, but it frequently leads to ventilator-induced lung injury (VILI). Understanding the pathophysiological processes involved in the development of VILI is an essential prerequisite for improving lung-protective ventilation strategies. The goal of this study was to relate the amount and nature of material accumulated in the airspaces to biomarkers of injury and the derecruitment behavior of the lung in VILI. Forty-nine BALB/c mice were mechanically ventilated with combinations of tidal volume and end-expiratory pressures to produce varying degrees of overdistension and atelectasis while lung function was periodically assessed. Total protein, serum protein, and E-Cadherin levels were measured in bronchoalveolar lavage fluid (BALF). Tissue injury was assessed by histological scoring. We found that both high tidal volume and zero positive end-expiratory pressure were necessary to produce significant VILI. Increased BALF protein content was correlated with increased lung derecruitability, elevated peak pressures, and histological evidence of tissue injury. Blood derived molecules were present in the BALF in proportion to histological injury scores and epithelial injury, reflected by E-Cadherin levels in BALF. We conclude that repetitive recruitment is an important factor in the pathogenesis of VILI that exacerbates injury associated with tidal overdistension. Furthermore, the dynamic mechanical behavior of the injured lung provides a means to assess both the degree of tissue injury and the nature and amount of blood-derived fluid and proteins that accumulate in the airspaces.
Highlights
Mechanical ventilation is necessary for managing the respiratory failure that defines acute respiratory distress syndrome (ARDS) (Force et al, 2012)
In the High-Vt/PEEP0 group the ventilator cylinder displacement was set to Vt = 55 ml/kg with the average delivered Vt = 44 ml/kg due to gas compression in the ventilator circuit
Our results show that there is a strong relationship between the derecruitability of the injured lung (Figure 2B) and the magnitude of the alveolar leak as reflected in the amount (Figure 2D) and nature of material accumulated in the airspaces
Summary
Mechanical ventilation is necessary for managing the respiratory failure that defines acute respiratory distress syndrome (ARDS) (Force et al, 2012). Mechanical ventilation itself can cause further damage to an already injured alveolar blood-gas barrier (Thammanomai et al, 2013) This allows additional leak of blood-derived materials into the airspaces where they impair surfactant function and raise surface tension (Holm and Notter, 1987; Holm et al, 1988; Günther et al, 1996), thereby exacerbating the injurious stresses caused. Avoiding ventilator-induced lung injury (VILI) requires ventilating in a way that avoids damaging the alveolar barrier (Amato et al, 1998). Achieving this in practice in any given ARDS lung, is challenging because it is not possible to determine alveolar leak directly with the rapidity required to make appropriate adjustments to ventilator strategy before injury worsens. Measurements of lung mechanics can be made in an ongoing fashion with the necessary rapidity (Terragni et al, 2003), and have the potential to guide the application of mechanical ventilation in ARDS provided they can be linked to events occurring at the level of the alveolar leak
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