Alveolar leak develops by a rich-get-richer process in ventilator-induced lung injury

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Abstract

Acute respiratory distress syndrome (ARDS) is a life-threatening condition for which there are currently no medical therapies other than supportive care involving the application of mechanical ventilation. However, mechanical ventilation itself can worsen ARDS by damaging the alveolocapillary barrier in the lungs. This allows plasma-derived fluid and proteins to leak into the airspaces of the lung where they interfere with the functioning of pulmonary surfactant, which increases the stresses of mechanical ventilation and worsens lung injury. Once such ventilator-induced lung injury (VILI) is underway, managing ARDS and saving the patient becomes increasingly problematic. Maintaining an intact alveolar barrier thus represents a crucial management goal, but the biophysical processes that perforate this barrier remain incompletely understood. To study the dynamics of barrier perforation, we subjected initially normal mice to an injurious ventilation regimen that imposed both volutrauma (overdistension injury) and atelectrauma (injury from repetitive reopening of closed airspaces) on the lung, and observed the rate at which macromolecules of various sizes leaked into the airspaces as a function of the degree of overall injury. Computational modeling applied to our findings suggests that perforations in the alveolocapillary barrier appear and progress according to a rich-get-richer mechanism in which the likelihood of a perforation getting larger increases with the size of the perforation. We suggest that atelectrauma causes the perforations after which volutrauma expands them. This mechanism explains why atelectrauma appears to be essential to the initiation of VILI in a normal lung, and why atelectrauma and volutrauma then act synergistically once VILI is underway.

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Hamlington, K. L., Bates, J. H. T., Roy, G. S., Julianelle, A. J., Charlebois, C., Suki, B., & Smith, B. J. (2018). Alveolar leak develops by a rich-get-richer process in ventilator-induced lung injury. PLoS ONE, 13(3). https://doi.org/10.1371/journal.pone.0193934

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