Linking Physiological Biomarkers of Ventilator-Induced Lung Injury to a Rich-Get-Richer Mechanism of Injury Progression

Abstract

Mechanical ventilation is a crucial tool in the management of acute respiratory distress syndrome (ARDS), yet it may itself also further damage the lung in a phenomenon known as ventilatorinduced lung injury (VILI). We have previously shown in mice that volutrauma and atelectrauma act synergistically to cause VILI. We have also postulated that this synergy arises because of a rich-get-richer mechanism in which repetitive lung recruitment generates initial small holes in the blood-gas barrier which are then expanded by over-distension in a manner that favors large holes over small ones. In order to understand the causal link between this process and the derangements in lung mechanics associated with VILI, we developed a mathematical model that incorporates both atelectrauma and volutrauma to predict how the propensity of the lung to derecruit depends on the accumulation of plasma-derived fluid and proteins in the airspaces. We found that the model accurately predicts derecruitment in mice with experimentally induced VILI.

Modeling Lung Derecruitment in VILI Due to Fluid-Occlusion: The Role of Emergent Behavior

“…found µ c (t) = kt, where k is a constant, in injuriously ventilated mice. Since PEEP is zero and H is measured using small-amplitude perturbations in lung volume, we assume that P = 0 to a first approximation (Mori et al, 2018). D rate can thus be written as:…”

“…From our previous proposed model (Mori et al, 2018) we can relate Eq. 9 to H 1 when t is sufficiently large:…”

“…Finally, the resulting estimations of D rate from the derecruitability tests were fitted to Eq. 15, and the 95% joint confidence regions for s m and k were determined as described by Mori et al (2018).…”

“…We have previously shown in mice that, as VILI develops, the time-course of H 1 can be accurately accounted for in terms of the accumulated leak of plasma-derived material through holes in the blood-gas barrier (Mori et al, 2018). These holes appear to be generated by both atelectrauma and volutrauma acting synergistically in a rich-get-richer fashion (Hamlington et al, 2018a).…”

Dexmedetomidine attenuates ventilator-induced lung injury in rats by up-regulating NLRC3

“…VILI includes of direct mechanical damage and indirect biological damage, and current researches divide mechanical Original Article Dexmedetomidine attenuates ventilator-induced lung injury in rats by up-regulating NLRC3 damage into three parts: barotrauma, volutrauma and atelectrauma. Mechanical damage can mediate biotrauma through many pathways (4,5), during which the lung cell wall was damaged directly by external mechanical force, which results in a large release of cytokines in the alveolars and circulatory system to lead local or systemic inflammatory reactions subsequently (6). The mainly pathophysiological changes of VILI include the alveolar structural destruction, the increased pulmonary vascular permeability, the activation of inflammatory cells and inflammatory factors and the imbalance of oxidation and antioxidation, etc.…”