Research progress on mechanism of biotrauma caused by ventilation-induced lung injury / 中华危重病急救医学

Mechanical ventilation is an advanced life support treatment for patients with acute respiratory failure. While stabilizing respiratory function, it also acts as an injury factor to exacerbate or lead to lung injury, that is, ventilation-induced lung injury (VILI). There may be a more subtle form of damage to VILI known as "biotrauma". However, the mechanism of biotrauma in VILI is still unclear. This article intends to review the mechanism of biotrauma of VILI from the aspects of inflammatory response, oxidative stress and complement activation, in order to provide a new strategy for clinical prevention and treatment of biotrauma caused by VILI.

Molecular Mechanisms of Ventilator-Induced Lung Injury / 中华医学杂志(英文版)

<p><b>Objective</b>Mechanical ventilation (MV) has long been used as a life-sustaining approach for several decades. However, researchers realized that MV not only brings benefits to patients but also cause lung injury if used improperly, which is termed as ventilator-induced lung injury (VILI). This review aimed to discuss the pathogenesis of VILI and the underlying molecular mechanisms.</p><p><b>Data Sources</b>This review was based on articles in the PubMed database up to December 2017 using the following keywords: "ventilator-induced lung injury", "pathogenesis", "mechanism", and "biotrauma".</p><p><b>Study Selection</b>Original articles and reviews pertaining to mechanisms of VILI were included and reviewed.</p><p><b>Results</b>The pathogenesis of VILI was defined gradually, from traditional pathological mechanisms (barotrauma, volutrauma, and atelectrauma) to biotrauma. High airway pressure and transpulmonary pressure or cyclic opening and collapse of alveoli were thought to be the mechanisms of barotraumas, volutrauma, and atelectrauma. In the past two decades, accumulating evidence have addressed the importance of biotrauma during VILI, the molecular mechanism underlying biotrauma included but not limited to proinflammatory cytokines release, reactive oxygen species production, complement activation as well as mechanotransduction.</p><p><b>Conclusions</b>Barotrauma, volutrauma, atelectrauma, and biotrauma contribute to VILI, and the molecular mechanisms are being clarified gradually. More studies are warranted to figure out how to minimize lung injury induced by MV.</p>

An experiment on the pathogenesis of early biotrauma in ventilator-induced lung injury / 中华危重病急救医学

Objective To investigate the pathogenesis of early biotrauma in ventilator-induced lung injury (VILI).Methods Twenty-four 8-week-old male specific-pathogen-free Sprague-Dawley (SD) rats weighing 250-300 g were randomly divided into sham group (S group), conventional mechanical ventilation group (L group) and high tidal volume (VT) mechanical ventilation group (H group) with 8 rats in each group. All rats received tracheostomy after anesthesia. Rats in S group received no mechanical ventilation but breathe room air spontaneously. All other parameters of the ventilator were the same in both mechanical ventilation groups, and the fraction of oxygen was set to 0.21, the rats in L group received 7 mL/kg VT, and those in H group received 28 mL/kg VT. Four hours after ventilation all rats were sacrificed and the lung tissues were harvested for wet/dry (W/D) ratio. Pathological injury score was evaluated by hematoxylin and eosin (HE) staining. Transferase-mediated deoxyuridine triphosphate-biotin nick end labeling stain (TUNEL) was performed to count the apoptosis cell in lung epithelial. Western Blot was performed to evaluate hemi-channel protein Pannexin-1 expression in lung homogenate. Bronchoalveolar lavage fluid (BALF) was collected, and the concentration of lactate dehydrogenase (LDH), isoprostane, adenosine triphosphate (ATP) and white cell count in BALF were measured. Yo-pro-1/propidium iodide (PI) double stain was performed to evaluate early apoptosis cell in BALF.Results There was no significant difference in lung injury between S group and L group. Compared with S group and L group, rats in H group showed significant lung injury, represented as alveolar rupture, inflammatory cell infiltration, interstitial edema and airway epithelial exfoliation, and the lung W/D ratio was increased significantly (5.1±0.2 vs. 4.4±0.2, 4.3±0.4, bothP< 0.01), pathological score was significantly increased [4.00 (4.00, 8.00) vs. 1.00 (0, 4.00), 2.00 (0, 4.75), bothP< 0.01], the white cell in BALF was significantly increased (×106/L: 2.97±0.46 vs.1.03±0.26, 0.79±0.19, bothP< 0.01), the level of LDH was significantly increased (U/L: 148.6±38.2 vs. 34.4±13.5, 78.6±13.9, bothP< 0.01), and the expression of Pannexin-1 in lung homogenate was significantly increased (Pannexin-1/GAPDH: 0.89±0.21 vs. 0.48±0.25, 0.61±0.17, bothP< 0.01), the ATP concentration in BALF was also significantly increased (nmol/L: 456.84±148.72 vs. 19.23±13.34, 113.26±57.90, bothP< 0.01). There was no significant difference in the apoptosis cell in lung tissue or the apoptosis cell rate, isoprostane level in BALF among the three groups [apoptosis cell in lung (cells/HP): 4.00 (3.00, 5.00) vs. 5.00 (4.00, 6.00), 4.00 (3.25, 6.00); apoptosis cell rate in BALF: (0.57±0.20)％ vs. (0.42±0.16)％, (0.58±0.19)％; isoprostane in BALF (μg/L): 3.85±0.46 vs. 3.83±0.60, 3.59±0.69, allP > 0.05].Conclusion The early pathogenesis of biotrauma in VILI is related to the release of inflammation mediator via membrane channel after activating by pressure stress, but not apoptosis and lipid peroxidation.

New progress of pathogenesis in ventilator-induced lung injury / 中华危重病急救医学

Mechanical ventilation is not only an important treatment method of acute respiratory distress syndrome (ARDS),but also one of the basic treatments in the intensive care unit (ICU).However,mechanical ventilation itself can cause or aggravate acute lung injury,which is called ventilator-induced lung injury (VILI).Currently,clinical pathogenesis of VILI includes four categories such as barotrauma,volutrauma,atelectrauma and hiotrauma.The pathogenesis of mechanical injury has been widely accepted,but the biological injury pathogenesis is unclear.With further research,we found that in the late stage VILI patients occured proliferation of puhnonary fibrosis,which may be formed by partial epithelial-mesenchymal transdifferentiation (EMT).Further study of specific pathogenesis of biotrauma and ARDS pulmonary fibrosis proliferation could provide new ideas for the clinical treatment of VILI.