scholarly journals High Expression of CXCL10/CXCR3 in Ventilator-Induced Lung Injury Caused by High Mechanical Power

2022 ◽  
Vol 2022 ◽  
pp. 1-9
Author(s):  
Yongpeng Xie ◽  
Hui Zheng ◽  
Zhifang Mou ◽  
Yanli Wang ◽  
Xiaomin Li
Keyword(s):  
Mast Cells ◽  
Lung Injury ◽  
Mrna Expression ◽  
Rat Plasma ◽  
Lung Damage ◽  
Mechanical Power ◽  
Ventilator Induced Lung Injury ◽  
Rat Lungs ◽  
Potential Biomarker ◽  
Power Group

Background. The energy delivered by a ventilator to the respiratory system in one minute is defined as mechanical power (MP). However, the effect of ventilator-induced lung injury (VILI) in patients suffering from acute respiratory distress syndrome (ARDS) is still unknown. Our previous studies revealed that CXCL10 may be a potential biomarker of lung injury in ARDS. Therefore, the aim of this study was to compare the lung injury of rats and patients under different MP conditions to explore the involvement of CXCL10 and its receptor CXCR3 in VILI. Methods. Patients were divided into the high mechanical power group (HMPp group) and low mechanical power group (LMPp group), while rats were assigned to the high mechanical power group (HMPr group), medium mechanical power group (MMPr group), and low mechanical power group (LMPr group). CXCL10 and CXCR3 plasma content in ARDS patients and rats under ventilation at different MP was measured, as well as their protein and mRNA expression in rat lungs. Results. CXCL10 and CXCR3 content in the plasma of ARDS patients in the HMPp was significantly higher than that in the LMPp. The increase of MP during mechanical ventilation in the rats gradually increased lung damage, and CXCL10 and CXCR3 levels in rat plasma gradually increased with the increase of MP. CXCL10 and CXCR3 protein and mRNA expression in the HMPr group and MMPr group was significantly higher than that in the LMPr group ( P < 0.05 ). More mast cells were present in the trachea, bronchus, blood vessels, and lymphatic system in the rat lungs of the HMPr group, and the number of mast cells in the HMPr group ( 13.32 ± 3.27 ) was significantly higher than that in the LMPr group ( 3.25 ± 0.29 ) ( P < 0.05 ). Conclusion. The higher the MP, the more severe the lung injury, and the higher the CXCL10/CXCR3 expression. Therefore, CXCL10/CXCR3 might participate in VILI by mediating mast cell chemotaxis.

scholarly journals High Expression of CXCL10/CXCR3 in Ventilator-Induced Lung Injury Caused by High Mechanical Power

2021 ◽  
Author(s):  
Yongpeng Xie ◽  
Hui Zheng ◽  
Zhifang Mou ◽  
Yanli Wang ◽  
Xiaomin Li
Keyword(s):  
Mast Cells ◽  
Lung Injury ◽  
Mrna Expression ◽  
Rat Plasma ◽  
Lung Damage ◽  
Mechanical Power ◽  
Ventilator Induced Lung Injury ◽  
Rat Lungs ◽  
Potential Biomarker ◽  
Power Group

Abstract Background: The energy delivered by a ventilator to the respiratory system in one minute is defined as mechanical power (MP). However, the effect of the ventilator-induced lung injury (VILI) in patients suffering of acute respiratory distress syndrome (ARDS) is still unknown. Our previous studies revealed that CXCL10 may be a potential biomarker of lung injury in ARDS. Therefore, the aim of this study was to compare the lung injury of rats and patients under different MP conditions to explore the involvement of CXCL10 and its receptor CXCR3 in VILI. Methods: Patients were divided into high mechanical power group (HMP) and low mechanical power group (LMP), while rats were assigned to the high mechanical power group (HMP), medium mechanical power group (MMP) and low mechanical power group (LMP). CXCL10 and CXCR3 plasma content in ARDS patients and rats under ventilation at different MP was measured, as well as their protein and mRNA expression in rat lungs. Results: CXCL10 and CXCR3 content in the plasma of ARDS patients in the HMP was significantly higher than that in the LMP. The increase of MP during mechanical ventilation in the rats gradually increased lung damage, and CXCL10 and CXCR3 level in rat plasma gradually increased with the increase of MP. CXCL10 and CXCR3 protein and mRNA expression in the HMP group and MMP group was significantly higher than that in the LMP group (P<0.05). More mast cells were present in the trachea, bronchus, blood vessels, and lymphatic system in the rat lungs of the HMP group and the number of mast cells in the HMP group (13.32±3.27) was significantly higher than that in the LMP group (3.25±0.29) (P＜0.05). Conclusion: The higher the MP, the more severe the lung injury, the higher CXCL10/CXCR3 expression. Therefore, CXCL10/CXCR3 might participate in VILI by mediating mast cell chemotaxis.

Exposure to mechanical ventilation promotes tolerance to ventilator-induced lung injury by Ccl3 downregulation

2015 ◽  
Vol 309 (8) ◽  
pp. L847-L856 ◽  
Author(s):  
Jorge Blázquez-Prieto ◽  
Inés López-Alonso ◽  
Laura Amado-Rodríguez ◽  
Estefanía Batalla-Solís ◽  
Adrián González-López ◽  
...  
Keyword(s):  
High Pressure ◽  
Lung Injury ◽  
Molecular Mechanisms ◽  
Peak Pressure ◽  
Lung Damage ◽  
Previous Exposure ◽  
Neutrophilic Infiltration ◽  
Ventilator Induced Lung Injury ◽  
Inflammatory Protein ◽  
Albumin Content

Inflammation plays a key role in the development of ventilator-induced lung injury (VILI). Preconditioning with a previous exposure can damp the subsequent inflammatory response. Our objectives were to demonstrate that tolerance to VILI can be induced by previous low-pressure ventilation, and to identify the molecular mechanisms responsible for this phenomenon. Intact 8- to 12-wk-old male CD1 mice were preconditioned with 90 min of noninjurious ventilation [peak pressure 17 cmH2O, positive end-expiratory pressure (PEEP) 2 cmH2O] and extubated. Seven days later, preconditioned mice and intact controls were submitted to injurious ventilation (peak pressure 20 cmH2O, PEEP 0 cmH2O) for 2 h to induce VILI. Preconditioned mice showed lower histological lung injury scores, bronchoalveolar lavage albumin content, and lung neutrophilic infiltration after injurious ventilation, with no differences in Il6 or Il10 expression. Microarray analyses revealed a downregulation of Calcb, Hspa1b, and Ccl3, three genes related to tolerance phenomena, in preconditioned animals. Among the previously identified genes, only Ccl3, which encodes the macrophage inflammatory protein 1 alpha (MIP-1α), showed significant differences between intact and preconditioned mice after high-pressure ventilation. In separate, nonconditioned animals, treatment with BX471, a specific blocker of CCR1 (the main receptor for MIP-1α), decreased lung damage and neutrophilic infiltration caused by high-pressure ventilation. We conclude that previous exposure to noninjurious ventilation induces a state of tolerance to VILI. Downregulation of the chemokine gene Ccl3 could be the mechanism responsible for this effect.

Ventilator-Induced Lung Injury Is Associated with Neutrophil Infiltration, Macrophage Activation, and TGF-β1 mRNA Upregulation in Rat Lungs

2001 ◽  
Vol 92 (2) ◽  
pp. 428-436 ◽  
Author(s):  
Hideaki Imanaka ◽  
Motomu Shimaoka ◽  
Nariaki Matsuura ◽  
Masaji Nishimura ◽  
Noriyuki Ohta ◽  
...  
Keyword(s):  
Lung Injury ◽  
Macrophage Activation ◽  
Neutrophil Infiltration ◽  
Ventilator Induced Lung Injury ◽  
Rat Lungs ◽  
Tgf Β1

CYCLIN-DEPENDENT KINASE INHIBITION REDUCES LUNG DAMAGE IN A MOUSE MODEL OF VENTILATOR-INDUCED LUNG INJURY

Shock ◽  
2012 ◽  
Vol 38 (4) ◽  
pp. 375-380 ◽  
Author(s):  
Arie J. Hoogendijk ◽  
Maria T. Kuipers ◽  
Tom van der Poll ◽  
Marcus J. Schultz ◽  
Catharina W. Wieland
Keyword(s):  
Lung Injury ◽  
Mouse Model ◽  
Lung Damage ◽  
Cyclin Dependent Kinase ◽  
Kinase Inhibition ◽  
Ventilator Induced Lung Injury

scholarly journals Bubble CPAP Support after Discontinuation of Mechanical Ventilation Protects Rat Lungs with Ventilator-Induced Lung Injury

Respiration ◽  
2016 ◽  
Vol 91 (2) ◽  
pp. 171-179 ◽  
Author(s):  
Chun Shan Wu ◽  
Hsiu Chu Chou ◽  
Liang Ti Huang ◽  
Yen Kuang Lin ◽  
Chung Ming Chen
Keyword(s):  
Mechanical Ventilation ◽  
Lung Injury ◽  
Ventilator Induced Lung Injury ◽  
Rat Lungs ◽  
Bubble Cpap

scholarly journals Experimental Ventilator-induced Lung Injury

2009 ◽  
Vol 110 (6) ◽  
pp. 1341-1347 ◽  
Author(s):  
Jesús Villar ◽  
Maria Teresa Herrera-Abreu ◽  
Francisco Valladares ◽  
Mercedes Muros ◽  
Lina Pérez-Méndez ◽  
...  
Keyword(s):  
Lung Injury ◽  
Fatal Outcome ◽  
Experimental Studies ◽  
Lung Damage ◽  
Cytokine Gene Expression ◽  
High Peep ◽  
Necrosis Factor Alpha ◽  
Ventilator Induced Lung Injury ◽  
Airway Pressures

Background Previous experimental studies of ventilator-induced lung injury have shown that positive end-expiratory pressure (PEEP) is protective. The authors hypothesized that the application of PEEP during volume-controlled ventilation with a moderately high tidal volume (VT) in previously healthy in vivo rats does not attenuate ventilator-induced lung injury if the peak airway pressure markedly increases during the application of PEEP. Methods Sixty healthy, male Sprague-Dawley rats were anesthetized and randomized to be mechanically ventilated for 4 h at (1) VT of 6 ml/kg, (2) VT of 20 ml/kg, or (3) VT of 20 ml/kg plus 10 cm H2O of PEEP. Peak airway pressures, gas exchange, histologic evaluation, mortality, total lung tissue cytokine gene expression, and serum cytokine concentrations were analyzed. Results Peak airway pressures exceeded 30 cm H2O with high VT plus PEEP. All lungs ventilated with high VT had perivascular edema and inflammatory infiltrates. In addition, those ventilated with PEEP had small hemorrhages foci. Five animals from the high VT plus PEEP group died (P = 0.020). Animals ventilated with high VT (with or without PEEP) had a substantial increase in serum interleukin-6 (P = 0.0002), and those ventilated with high VT plus PEEP had a 5.5-fold increase in systemic levels of tumor necrosis factor-alpha (P = 0.007). Conclusions In contrast to previous reports, PEEP exacerbated lung damage and contributed to fatal outcome in an in vivo, mild overdistension model of ventilator-induced lung injury in previously healthy rats. That is, the addition of high PEEP to a constant large VT causes injury in previously healthy animals.

scholarly journals NADPH Oxidase 4 Signaling in a Ventilator-induced Lung Injury Mouse Model

2021 ◽  
Author(s):  
Sang Hoon Lee ◽  
Mi Hwa Shin ◽  
Ah Young Leem ◽  
Su Hwan Lee ◽  
Kyung Soo Chung ◽  
...  
Keyword(s):  
Lung Injury ◽  
Lavage Fluid ◽  
Lung Damage ◽  
Control Group ◽  
Group 4 ◽  
Ventilator Induced Lung Injury ◽  
Cell Counts ◽  
Group 5 ◽  
Group 2

Abstract For patients with acute respiratory distress syndrome, a ventilator is essential to supply oxygen to tissues, but it may also cause lung damage. We investigated the role of NOX4 in a ventilator-induced lung injury (VILI) model.Wild-type (WT) male C57BL/6J mice and NOX4 knockout (KO) male mice were divided into five groups: (1) control group; (2) high tidal ventilation (HTV) group: WT mice + HTV; (3) NOX4 KO group; (4) NOX4 KO with HTV group; (5) NOX4 inhibitor group: WT mice + HTV + NOX4 inhibitor. In addition, the relationship between EphA2 (which is related to lung injury) and NOX4 was investigated using EphA2 KO mice, and NOX4 levels in the bronchoalveolar lavage fluid (BALF) of 38 patients with pneumonia were examined.In the NOX4 inhibitor group, cell counts and protein concentrations from BALF were significantly lower than those in the HTV group (both, p<0.001). In the NOX4 KO group and the NOX4 inhibitor group, EphA2 levels were significantly lower than those in the HTV group (p<0.001). NOX4 levels were significantly higher in patients with pneumonia and patients who received ventilator treatment in the ICU.In the VILI model, it may be possible to block VILI using NOX4 antibodies.

scholarly journals Is mechanical power the final word on ventilator-induced lung injury?—no

2018 ◽  
Vol 6 (19) ◽  
pp. 394-394 ◽  
Author(s):  
Robert Huhle ◽  
Ary Serpa Neto ◽  
Marcus J. Schultz ◽  
Marcelo Gama de Abreu
Keyword(s):  
Lung Injury ◽  
Mechanical Power ◽  
Final Word ◽  
Ventilator Induced Lung Injury

scholarly journals Hydrogen Sulfide Prevents Formation of Reactive Oxygen Species through PI3K/Akt Signaling and Limits Ventilator-Induced Lung Injury

2017 ◽  
Vol 2017 ◽  
pp. 1-14 ◽  
Author(s):  
Sashko Georgiev Spassov ◽  
Rosa Donus ◽  
Paul Mikael Ihle ◽  
Helen Engelstaedter ◽  
Alexander Hoetzel ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Hydrogen Sulfide ◽  
Lung Injury ◽  
Inflammatory Responses ◽  
Reactive Oxygen ◽  
Akt Signaling ◽  
Lung Damage ◽  
Oxygen Species ◽  
Ventilator Induced Lung Injury ◽  
Oxidative Processes

The development of ventilator-induced lung injury (VILI) is still a major problem in mechanically ventilated patients. Low dose inhalation of hydrogen sulfide (H2S) during mechanical ventilation has been proven to prevent lung damage by limiting inflammatory responses in rodent models. However, the capacity of H2S to affect oxidative processes in VILI and its underlying molecular signaling pathways remains elusive. In the present study we show that ventilation with moderate tidal volumes of 12 ml/kg for 6 h led to an excessive formation of reactive oxygen species (ROS) in mice lungs which was prevented by supplemental inhalation of 80 parts per million of H2S. In addition, phosphorylation of the signaling protein Akt was induced by H2S. In contrast, inhibition of Akt by LY294002 during ventilation reestablished lung damage, neutrophil influx, and proinflammatory cytokine release despite the presence of H2S. Moreover, the ability of H2S to induce the antioxidant glutathione and to prevent ROS production was reversed in the presence of the Akt inhibitor. Here, we provide the first evidence that H2S-mediated Akt activation is a key step in protection against VILI, suggesting that Akt signaling limits not only inflammatory but also detrimental oxidative processes that promote the development of lung injury.

scholarly journals Using injury cost functions from a predictive single-compartment model to assess the severity of mechanical ventilator-induced lung injuries

2019 ◽  
Vol 127 (1) ◽  
pp. 58-70 ◽  
Author(s):  
Michelle M. Mellenthin ◽  
Siyeon A. Seong ◽  
Gregory S. Roy ◽  
Elizabeth Bartolák-Suki ◽  
Katharine L. Hamlington ◽  
...  
Keyword(s):  
Lung Injury ◽  
Power Dissipation ◽  
Compartment Model ◽  
Mechanical Power ◽  
Cost Functions ◽  
Mechanical Ventilator ◽  
Ventilator Induced Lung Injury ◽  
Single Compartment ◽  
Single Compartment Model ◽  
Ventilator Settings

Identifying safe ventilation patterns for patients with acute respiratory distress syndrome remains challenging because of the delicate balance between gas exchange and selection of ventilator settings to prevent further ventilator-induced lung injury (VILI). Accordingly, this work seeks to link ventilator settings to graded levels of VILI to identify injury cost functions that predict injury by using a computational model to process pressures and flows measured at the airway opening. Pressure-volume loops were acquired over the course of ~2 h of mechanical ventilation in four different groups of BALB/c mice. A cohort of these animals were subjected to an injurious bronchoalveolar lavage before ventilation. The data were analyzed with a single-compartment model that predicts recruitment/derecruitment and tissue distension at each time step in measured pressure-volume loops. We compared several injury cost functions to markers of VILI-induced blood-gas barrier disruption. Of the cost functions considered, we conclude that mechanical power dissipation and strain heterogeneity are the best at distinguishing between graded levels of injury and are good candidates for forecasting the development of VILI. NEW & NOTEWORTHY This work uses a predictive single-compartment model and injury cost functions to assess graded levels of mechanical ventilator-induced lung injury. The most promising measures include strain heterogeneity and mechanical power dissipation.

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