scholarly journals Redox Balance and Cellular Inflammation in the Diaphragm, Limb Muscles, and Lungs of Mechanically Ventilated Rats

2010 ◽  
Vol 112 (2) ◽  
pp. 384-394 ◽  
Author(s):  
Judith Marín-Corral ◽  
Leticia Martínez-Caro ◽  
José A. Lorente ◽  
Marta de Paula ◽  
Lara Pijuan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Mechanical Ventilation ◽  
Lung Injury ◽  
Protein Adducts ◽  
Organ Injury ◽  
Mechanically Ventilated ◽  
Ventilator Induced Lung Injury ◽  
Cellular Inflammation ◽  
Cell Counts ◽  
Limb Muscles

Background High tidal volume (VT) mechanical ventilation was shown to induce organ injury other than lung injury and systemic inflammation in animal models of ventilator-induced lung injury. The authors aimed to explore whether high VT mechanical ventilation per se induces early oxidative stress and inflammation in the diaphragm, limb muscles, and lungs of healthy rats exposed to ventilator-induced lung injury. Methods Protein carbonylation and nitration, antioxidants (immunoblotting), and inflammation (immunohistochemistry) were evaluated in the diaphragm, gastrocnemius, soleus, tibialis anterior, and lungs of mechanically ventilated healthy rats and in nonventilated control animals (n = 8/group) for 1 h, using two different strategies (moderate VT [VT = 9 ml/kg] and high VT [VT = 35 ml/kg]). Results The main findings are summarized as follows: compared with controls, (1) the diaphragms and gastrocnemius of high-VT rats exhibited a decrease in reactive carbonyls, (2) the soleus and tibialis of high- and moderate-VT rodents showed a reduction in reactive carbonyls and malondialdehyde-protein adducts, (3) the lungs of high-VT rats exhibited a significant rise in malondialdehyde-protein adducts, (4) the soleus and tibialis of both high- and moderate-VT rats showed a reduction in protein nitration, (5) the lungs of high- and moderate-VT rats showed a reduction in antioxidant enzyme levels, but not in the muscles, and (6) the diaphragms and gastrocnemius of all groups exhibited very low inflammatory cell counts, whereas the lungs of high-VT rats exhibited a significant increase in inflammatory infiltrates. Conclusions Although oxidative stress and inflammation increased in the lungs of rats exposed to high VT, the diaphragm and limb muscles exhibited a decline in oxidative stress markers and very low levels of cellular inflammation.

scholarly journals The Extent of Ventilator-Induced Lung Injury in Mice Partly Depends on Duration of Mechanical Ventilation

2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Maria A. Hegeman ◽  
Sabrine N. T. Hemmes ◽  
Maria T. Kuipers ◽  
Lieuwe D. J. Bos ◽  
Geartsje Jongsma ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Lung Injury ◽  
Capillary Permeability ◽  
Statistical Significance ◽  
Lung Compliance ◽  
Alveolar Cell ◽  
Mechanically Ventilated ◽  
Ventilator Induced Lung Injury ◽  
Cell Counts ◽  
Alveolar Capillary

Background. Mechanical ventilation (MV) has the potential to initiate ventilator-induced lung injury (VILI). The pathogenesis of VILI has been primarily studied in animal models using more or less injurious ventilator settings. However, we speculate that duration of MV also influences severity and character of VILI.Methods. Sixty-four healthy C57Bl/6 mice were mechanically ventilated for 5 or 12 hours, using lower tidal volumes with positive end-expiratory pressure (PEEP) or higher tidal volumes without PEEP. Fifteen nonventilated mice served as controls.Results. All animals remained hemodynamically stable and survived MV protocols. In both MV groups, PaO2to FiO2ratios were lower and alveolar cell counts were higher after 12 hours of MV compared to 5 hours. Alveolar-capillary permeability was increased after 12 hours compared to 5 hours, although differences did not reach statistical significance. Lung levels of inflammatory mediators did not further increase over time. Only in mice ventilated with increased strain, lung compliance declined and wet to dry ratio increased after 12 hours of MV compared to 5 hours.Conclusions. Deleterious effects of MV are partly dependent on its duration. Even lower tidal volumes with PEEP may initiate aspects of VILI after 12 hours of MV.

Tert-butylhydroquinone augments Nrf2-dependent resilience against oxidative stress and improves survival of ventilator-induced lung injury in mice

2021 ◽  
Vol 320 (1) ◽  
pp. L17-L28
Author(s):  
Lilly Veskemaa ◽  
Jan A. Graw ◽  
Philipp A. Pickerodt ◽  
Mahdi Taher ◽  
Willehad Boemke ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Gene Expression ◽  
Mechanical Ventilation ◽  
Lung Injury ◽  
Respiratory System ◽  
Arterial Oxygenation ◽  
Respiratory System Compliance ◽  
Proinflammatory Response ◽  
Ventilator Induced Lung Injury ◽  
Redox Capacity

Oxidative stress caused by mechanical ventilation contributes to the pathophysiology of ventilator-induced lung injury (VILI). A key mechanism maintaining redox balance is the upregulation of nuclear factor-erythroid-2-related factor 2 (Nrf2)-dependent antioxidant gene expression. We tested whether pretreatment with an Nrf2-antioxidant response element (ARE) pathway activator tert-butylhydroquinone (tBHQ) protects against VILI. Male C57BL/6J mice were pretreated with an intraperitoneal injection of tBHQ ( n = 10), an equivalent volume of 3% ethanol (EtOH3%, vehicle, n = 13), or phosphate-buffered saline (controls, n = 10) and were then subjected to high tidal volume (HVT) ventilation for a maximum of 4 h. HVT ventilation severely impaired arterial oxygenation ([Formula: see text] = 49 ± 7 mmHg, means ± SD) and respiratory system compliance, resulting in a 100% mortality among controls. Compared with controls, tBHQ improved arterial oxygenation ([Formula: see text] = 90 ± 41 mmHg) and respiratory system compliance after HVT ventilation. In addition, tBHQ attenuated the HVT ventilation-induced development of lung edema and proinflammatory response, evidenced by lower concentrations of protein and proinflammatory cytokines (IL-1β and TNF-α) in the bronchoalveolar lavage fluid, respectively. Moreover, tBHQ enhanced the pulmonary redox capacity, indicated by enhanced Nrf2-depentent gene expression at baseline and by the highest total glutathione concentration after HVT ventilation among all groups. Overall, tBHQ pretreatment resulted in 60% survival ( P < 0.001 vs. controls). Interestingly, compared with controls, EtOH3% reduced the proinflammatory response to HVT ventilation in the lung, resulting in 38.5% survival ( P = 0.0054 vs. controls). In this murine model of VILI, tBHQ increases the pulmonary redox capacity by activating the Nrf2-ARE pathway and protects against VILI. These findings support the efficacy of pharmacological Nrf2-ARE pathway activation to increase resilience against oxidative stress during injurious mechanical ventilation.

scholarly journals Interaction between regional lung volumes and ventilator-induced lung injury in the normal and endotoxemic lung

2020 ◽  
Vol 318 (3) ◽  
pp. L494-L499 ◽  
Author(s):  
Seiha Yen ◽  
Melissa Preissner ◽  
Ellen Bennett ◽  
Stephen Dubsky ◽  
Richard Carnibella ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Lung Injury ◽  
Tidal Volume ◽  
Lung Volumes ◽  
Mechanically Ventilated ◽  
Ventilator Induced Lung Injury ◽  
Computed Tomography Images ◽  
Gas Trapping ◽  
Regional Lung ◽  
The Relationship

Both overdistension and atelectasis contribute to lung injury and mortality during mechanical ventilation. It has been proposed that combinations of tidal volume and end-expiratory lung volume exist that minimize lung injury linked to mechanical ventilation. The aim of this study was to examine this at the regional level in the healthy and endotoxemic lung. Adult female BALB/c mice were injected intraperitoneally with 10 mg/kg lipopolysaccharide (LPS) in saline or with saline alone. Four hours later, mice were mechanically ventilated for 2 h. Regional specific end-expiratory volume (sEEV) and tidal volume (sVt) were measured at baseline and after 2 h of ventilation using dynamic high-resolution four-dimensional computed tomography images. The regional expression of inflammatory genes was quantified by quantitative PCR. There was a heterogenous response in regional sEEV whereby endotoxemia increased gas trapping at end-expiration in some lung regions. Within the healthy group, there was a relationship between sEEV, sVt, and the expression of Tnfa, where high Vt in combination with high EEV or very low EEV was associated with an increase in gene expression. In endotoxemia there was an association between low sEEV, particularly when this was combined with moderate sVt, and high expression of IL6. Our data suggest that preexisting systemic inflammation modifies the relationship between regional lung volumes and inflammation and that although optimum EEV-Vt combinations to minimize injury exist, further studies are required to identify the critical inflammatory mediators to assess and the effect of different injury types on the response.

scholarly journals Imaging atelectrauma in Ventilator-Induced Lung Injury using 4D X-ray microscopy

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Luca Fardin ◽  
Ludovic Broche ◽  
Goran Lovric ◽  
Alberto Mittone ◽  
Olivier Stephanov ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Lung Injury ◽  
Lung Parenchyma ◽  
Contrast Imaging ◽  
Barrier Dysfunction ◽  
Mechanically Ventilated ◽  
Ventilator Induced Lung Injury ◽  
Regional Lung ◽  
Ventilation Strategies ◽  
Protective Mechanical Ventilation

AbstractMechanical ventilation can damage the lungs, a condition called Ventilator-Induced Lung Injury (VILI). However, the mechanisms leading to VILI at the microscopic scale remain poorly understood. Here we investigated the within-tidal dynamics of cyclic recruitment/derecruitment (R/D) using synchrotron radiation phase-contrast imaging (PCI), and the relation between R/D and cell infiltration, in a model of Acute Respiratory Distress Syndrome in 6 anaesthetized and mechanically ventilated New-Zealand White rabbits. Dynamic PCI was performed at 22.6 µm voxel size, under protective mechanical ventilation [tidal volume: 6 ml/kg; positive end-expiratory pressure (PEEP): 5 cmH2O]. Videos and quantitative maps of within-tidal R/D showed that injury propagated outwards from non-aerated regions towards adjacent regions where cyclic R/D was present. R/D of peripheral airspaces was both pressure and time-dependent, occurring throughout the respiratory cycle with significant scatter of opening/closing pressures. There was a significant association between R/D and regional lung cellular infiltration (p = 0.04) suggesting that tidal R/D of the lung parenchyma may contribute to regional lung inflammation or capillary-alveolar barrier dysfunction and to the progression of lung injury. PEEP may not fully mitigate this phenomenon even at high levels. Ventilation strategies utilizing the time-dependence of R/D may be helpful in reducing R/D and associated injury.

scholarly journals Simultaneous Pretreatment of Aspirin and Omega-3 Fatty Acid Attenuates Nuclear Factor-κB Activation in a Murine Model with Ventilator-Induced Lung Injury

Nutrients ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 2258
Author(s):  
Won-Gun Kwack ◽  
Yoon-Je Lee ◽  
Eun-Young Eo ◽  
Jin-Haeng Chung ◽  
Jae-Ho Lee ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Fatty Acid ◽  
Lung Injury ◽  
Nuclear Factor Κb ◽  
Nuclear Factor ◽  
Omega 3 ◽  
Omega 3 Fatty Acid ◽  
Ventilator Induced Lung Injury ◽  
Sequential Administration ◽  
Pretreated Group

Ventilator-induced lung injury (VILI) is an important critical care complication. Nuclear factor-κB (NF-κB) activation, a critical signaling event in the inflammatory response, has been implicated in the tracking of the lung injury. The present study aimed to determine the effect of simultaneous pretreatment with enteral aspirin and omega-3 fatty acid on lung injury in a murine VILI model. We compared the lung inflammation after the sequential administration of lipopolysaccharides and mechanical ventilation between the pretreated simultaneous enteral aspirin and omega-3 fatty acid group and the non-pretreatment group, by quantifying NF-κB activation using an in vivo imaging system to detect bioluminescence signals. The pretreated group with enteral aspirin and omega-3 fatty acid exhibited a smaller elevation of bioluminescence signals than the non-pretreated group (p = 0.039). Compared to the non-pretreated group, the pretreatment group with simultaneous enteral aspirin and omega-3 fatty acid showed reduced expression of the pro-inflammatory cytokine, tumor necrosis factor-α, in bronchoalveolar lavage fluid (p = 0.038). Histopathological lung injury scores were also lower in the pretreatment groups compared to the only injury group. Simultaneous pretreatment with enteral administration of aspirin and omega-3 fatty acid could be a prevention method for VILI in patients with impending mechanical ventilation therapy.

Oxidative stress and inflammation contribute to lung toxicity after a common breast cancer chemotherapy regimen

2002 ◽  
Vol 283 (2) ◽  
pp. L336-L345 ◽  
Author(s):  
Amir M. Abushamaa ◽  
Thomas A. Sporn ◽  
Rodney J. Folz
Keyword(s):  
Breast Cancer ◽  
Oxidative Stress ◽  
Lung Injury ◽  
Inflammatory Response ◽  
Chemotherapeutic Agents ◽  
Total Cell ◽  
Lung Toxicity ◽  
High Dose ◽  
Cell Counts ◽  
Cellular Inflammatory Response

Delayed pulmonary toxicity syndrome after high-dose chemotherapy (HDC) and autologous hematopoietic support occurs in up to 64% of women with advanced-stage breast cancer. Using a similar, but nonmyeloablative, HDC treatment regimen in mice, we found both immediate and persistent lung injury, coincident with marked decreases in lung tissue glutathione reductase activity and accompanied by increases in lung oxidized glutathione, bronchoalveolar lavage (BAL) lipid peroxidation, and BAL total cell counts. Most interestingly, at 6 wk, BAL total cell counts had increased fourfold, with lymphocyte cell counts increasing >11-fold. A single supplemental dose of glutathione prevented early lung injury at 48 h but showed no lung-protective effects at 6 wk, whereas single doses of other thiol-sparing agents (Ethyol and glutathione monoethyl ester) showed no benefit. These data suggest that this HDC regimen results in acute and persistent lung toxicity, induced in part by oxidative stress, that culminates with an acute lung cellular inflammatory response. Continuous glutathione supplementation and/or attenuation of the delayed pulmonary inflammatory response may prove beneficial in preventing lung toxicity after the use of these chemotherapeutic agents.

Noninvasive and Invasive Ventilatory Support II

2018 ◽  
Author(s):  
Pauline K. Park ◽  
Nicole L Werner ◽  
Carl Haas
Keyword(s):  
Mechanical Ventilation ◽  
Respiratory Failure ◽  
Lung Injury ◽  
Acute Respiratory Failure ◽  
Ventilatory Support ◽  
Underlying Disease ◽  
Protective Ventilation ◽  
Lung Protective Ventilation ◽  
Pulmonary Mechanics ◽  
Ventilator Induced Lung Injury

Invasive and noninvasive ventilation are important tools in the clinician’s armamentarium for managing acute respiratory failure. Although these modalities do not treat the underlying disease, they can provide the necessary oxygenation and ventilatory support until the causal pathology resolves. Care must be taken as even appropriate application can cause harm. Knowledge of pulmonary mechanics, appreciation of the basic machine settings, and an understanding of how common and advanced modes function allows the clinician to optimally tailor support to the patient while limiting iatrogenic injury. This second chapter reviews indications for mechanical ventilation, routine management, troubleshooting, and liberation from mechanical ventilation This review contains 6 figures, 7 tables and 60 references Keywords: Mechanical ventilation, lung protective ventilation, sedation, ventilator-induced lung injury, liberation from mechanical ventilation 

scholarly journals Cecal ligation and puncture accelerates development of ventilator-induced lung injury

2015 ◽  
Vol 308 (5) ◽  
pp. L443-L451 ◽  
Author(s):  
Nadir Yehya ◽  
Yi Xin ◽  
Yousi Oquendo ◽  
Maurizio Cereda ◽  
Rahim R. Rizi ◽  
...  
Keyword(s):  
Computed Tomography ◽  
Mechanical Ventilation ◽  
Lung Injury ◽  
Pulmonary Inflammation ◽  
Cecal Ligation ◽  
Interleukin 1Β ◽  
Sham Operation ◽  
Cecal Ligation And Puncture ◽  
Sprague Dawley ◽  
Ventilator Induced Lung Injury

Sepsis is a leading cause of respiratory failure requiring mechanical ventilation, but the interaction between sepsis and ventilation is unclear. While prior studies demonstrated a priming role with endotoxin, actual septic animal models have yielded conflicting results regarding the role of preceding sepsis on development of subsequent ventilator-induced lung injury (VILI). Using a rat cecal ligation and puncture (CLP) model of sepsis and subsequent injurious ventilation, we sought to determine if sepsis affects development of VILI. Adult male Sprague-Dawley rats were subject to CLP or sham operation and, after 12 h, underwent injurious mechanical ventilation (tidal volume 30 ml/kg, positive end-expiratory pressure 0 cmH2O) for either 0, 60, or 120 min. Biochemical and physiological measurements, as well as computed tomography, were used to assess injury at 0, 60, and 120 min of ventilation. Before ventilation, CLP rats had higher levels of alveolar neutrophils and interleukin-1β. After 60 min of ventilation, CLP rats had worse injury as evidenced by increased alveolar inflammation, permeability, respiratory static compliance, edema, oxygenation, and computed tomography. By 120 min, CLP and sham rats had comparable levels of lung injury as assessed by many, but not all, of these metrics. CLP rats had an accelerated and worse loss of end-expiratory lung volume relative to sham, and consistently higher levels of alveolar interleukin-1β. Loss of aeration and progression of edema was more pronounced in dependent lung regions. We conclude that CLP initiated pulmonary inflammation in rats, and accelerated the development of subsequent VILI.

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