scholarly journals Different Tidal Volumes May Jeopardize Pulmonary Redox and Inflammatory Status in Healthy Rats Undergoing Mechanical Ventilation

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Leandro da Silva Cândido ◽  
Natália Alves de Matos ◽  
Thalles de Freitas Castro ◽  
Laisy Cristina de Paula ◽  
Aline Maria dos Santos ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Lung Injury ◽  
Lung Tissue ◽  
Tissue Homogenate ◽  
Control Group ◽  
Adult Rats ◽  
Redox Imbalance ◽  
Inflammatory Status ◽  
Arterial Blood ◽  
Lung Tissue Homogenate

Mechanical ventilation (MV) is essential for the treatment of critical patients since it may provide a desired gas exchange. However, MV itself can trigger ventilator-associated lung injury in patients. We hypothesized that the mechanisms of lung injury through redox imbalance might also be associated with pulmonary inflammatory status, which has not been so far described. We tested it by delivering different tidal volumes to normal lungs undergoing MV. Healthy Wistar rats were divided into spontaneously breathing animals (control group, CG), and rats were submitted to MV (controlled ventilation mode) with tidal volumes of 4 mL/kg (MVG4), 8 mL/kg (MVG8), or 12 mL/kg (MVG12), zero end-expiratory pressure (ZEEP), and normoxia ( Fi O 2 = 21 % ) for 1 hour. After ventilation and euthanasia, arterial blood, bronchoalveolar lavage fluid (BALF), and lungs were collected for subsequent analysis. MVG12 presented lower PaCO2 and bicarbonate content in the arterial blood than CG, MVG4, and MVG8. Neutrophil influx in BALF and MPO activity in lung tissue homogenate were significantly higher in MVG12 than in CG. The levels of CCL5, TNF-α, IL-1, and IL-6 in lung tissue homogenate were higher in MVG12 than in CG and MVG4. In the lung parenchyma, the lipid peroxidation was more important in MVG12 than in CG, MVG4, and MVG8, while there was more protein oxidation in MVG12 than in CG and MVG4. The stereological analysis confirmed the histological pulmonary changes in MVG12. The association of controlled mode ventilation and high tidal volume, without PEEP and normoxia, impaired pulmonary histoarchitecture and triggered redox imbalance and lung inflammation in healthy adult rats.

scholarly journals Protective Effect of Corynoline in Sepsis-Induced Acute Lung Injury in Rats via Inhibition of NF-ĸB

2020 ◽  
Vol 15 (11) ◽  
pp. 1934578X2096118
Author(s):  
Min Shu ◽  
Yulu Tang ◽  
Jianzhen Liu
Keyword(s):  
Oxidative Stress ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Protective Effect ◽  
Lung Tissue ◽  
Significant Inhibition ◽  
Tissue Homogenate ◽  
Necrosis Factor Alpha ◽  
Lung Tissue Homogenate ◽  
And Migration

The present study was conducted to determine the effect of corynoline (COR) against sepsis-induced acute lung injury (ALI) in Wistar rats. Results of the study suggested that COR causes significant inhibition of lipid peroxidation (malondialdehyde) together with inhibition of oxidative stress (superoxide dismutase, catalase, glutathione peroxidase, and myeloperoxidase). The level of various proinflammatory (tumor necrosis factor-alpha, interleukin-8, and migration inhibitory factor) was also found to be reduced in COR-treated rats after sepsis. The protective effect of COR was further substantiated by the histopathology of lung tissue, where it improves the architecture of alveolar spaces. In western blot analysis, COR causes significant inhibition of nuclear factor kappa-light-chain-enhancer of activated B cells activation in the lung tissue homogenate. Our results demonstrated that COR was able to prevent the progression of ALI in rats via inhibition of inflammation and oxidative stress.

Molecular mechanism of TLR4 mediated T cell immune effect in transfusion-induced acute lung injury based on Slit2/Robo4 signaling pathway

2020 ◽  
Vol 13 ◽  
Author(s):  
Kun Xiao ◽  
Fei Zhao ◽  
WenJie Xie ◽  
Jian Ding ◽  
XiaoAn Gong ◽  
...  
Keyword(s):  
T Cell ◽  
Signaling Pathway ◽  
Molecular Mechanism ◽  
Lung Tissue ◽  
Acute Injury ◽  
Tissue Homogenate ◽  
Control Group ◽  
Pathological Features ◽  
Mhc I ◽  
Immune Effect

Objective: To explore and investigate the molecular mechanism of TLR4 mediated T cell immune effect in transfusion-induced acute injury based on SLIT2/ROBO4 signaling pathway. Methods: Sixty C57/BL6 male mice (Wild type, WT) aged 8 to 10 weeks were randomly divided into 5 groups: 1) normal type WT, 2) LPS control group of WT type lipopolysaccharide, 3) WT type TRALI group (LPS + MHC-I mAb), 4) (TLR4 antibody) lipopolysaccharide LPS control group, 5) (TLR4 antibody) TRALI group (LPS + MHC-I mAb). Mice were dosed with LPS (0.1 mg / kg), and MHC-I mAb (2 mg / kg) was injected into the tail vein 24 hours later for modeling. After 2 hours, mice were sacrificed and experimental samples were collected. HE staining was performed to detect pathological features. The myeloperoxidase (MPO) activity and the level of IL-2, IL-6, TNF, IFN-γ, IL-17A as well as IL-10 were measured in the lung tissue homogenate supernatant. Blood, spleen single cell suspension and bronchoalveolar lavage fluid (BALF) were collected to detect the ratio of Treg and Th17 cells by flow cytometry, respectively. RT-PCR and WB indicated the mRNA or protein expression of CDH5 (Cadherin-5), SLIT2 and ROBO4 in mouse lung tissue and pulmonary vascular tissue respectively. Results: TLR4 mAb treatment decreases the pathological features of LPS induced ALI model in vivo. And so does the MPO activity as well as the level of proinflammatory factors in the lung tissue. TLR4 exerts its function through the changes of Treg/Th17 ratio via SLIT2/ROBO4 signaling pathway and downregulating CDH5 and SETSIP in ALI model. Conclusion: TLR4 mediates immune response in LPS induced ALI model through SLIT2/ROBO4 signaling pathway.

Alterations to surfactant precede physiological deterioration during high tidal volume ventilation

2008 ◽  
Vol 294 (5) ◽  
pp. L974-L983 ◽  
Author(s):  
Adam A. Maruscak ◽  
Daniel W. Vockeroth ◽  
Brandon Girardi ◽  
Tanya Sheikh ◽  
Fred Possmayer ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Lung Injury ◽  
Tidal Volume ◽  
Blood Oxygenation ◽  
Exogenous Surfactant ◽  
Ventilation Strategy ◽  
Adult Rats ◽  
Lung Dysfunction ◽  
And Function ◽  
Over Time

Lung injury due to mechanical ventilation is associated with an impairment of endogenous surfactant. It is unknown whether this impairment is a consequence of or an active contributor to the development and progression of lung injury. To investigate this issue, the present study addressed three questions: Do alterations to surfactant precede physiological lung dysfunction during mechanical ventilation? Which components are responsible for surfactant's biophysical dysfunction? Does exogenous surfactant supplementation offer a physiological benefit in ventilation-induced lung injury? Adult rats were exposed to either a low-stretch [tidal volume (Vt) = 8 ml/kg, positive end-expiratory pressure (PEEP) = 5 cmH2O, respiratory rate (RR) = 54–56 breaths/min (bpm), fractional inspired oxygen (FiO2) = 1.0] or high-stretch (Vt = 30 ml/kg, PEEP = 0 cmH2O, RR = 14–16 bpm, FiO2 = 1.0) ventilation strategy and monitored for either 1 or 2 h. Subsequently, animals were lavaged and the composition and function of surfactant was analyzed. Separate groups of animals received exogenous surfactant after 1 h of high-stretch ventilation and were monitored for an additional 2 h. High stretch induced a significant decrease in blood oxygenation after 2 h of ventilation. Alterations in surfactant pool sizes and activity were observed at 1 h of high-stretch ventilation and progressed over time. The functional impairment of surfactant appeared to be caused by alterations to the hydrophobic components of surfactant. Exogenous surfactant treatment after a period of high-stretch ventilation mitigated subsequent physiological lung dysfunction. Together, these results suggest that alterations of surfactant are a consequence of the ventilation strategy that impair the biophysical activity of this material and thereby contribute directly to lung dysfunction over time.

Biomarkers for oxidative stress in acute lung injury induced in rabbits submitted to different strategies of mechanical ventilation

2012 ◽  
Vol 112 (7) ◽  
pp. 1184-1190 ◽  
Author(s):  
Carlos Fernando Ronchi ◽  
Jose Roberto Fioretto ◽  
Ana Lucia Anjos Ferreira ◽  
Carolina Bragiola Berchieri-Ronchi ◽  
Camila Renata Correa ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Mechanical Ventilation ◽  
Dna Damage ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Comet Assay ◽  
Lung Tissue ◽  
Significant Positive Correlation ◽  
Target Tissue ◽  
Total Antioxidant

Oxidative damage has been said to play an important role in pulmonary injury, which is associated with the development and progression of acute respiratory distress syndrome (ARDS). We aimed to identify biomarkers to determine the oxidative stress in an animal model of acute lung injury (ALI) using two different strategies of mechanical ventilation. Rabbits were ventilated using either conventional mechanical ventilation (CMV) or high-frequency oscillatory ventilation (HFOV). Lung injury was induced by tracheal saline infusion (30 ml/kg, 38°C). In addition, five healthy rabbits were studied for oxidative stress. Isolated lymphocytes from peripheral blood and lung tissue samples were analyzed by alkaline single cell gel electrophoresis (comet assay) to determine DNA damage. Total antioxidant performance (TAP) assay was applied to measure overall antioxidant performance in plasma and lung tissue. HFOV rabbits had similar results to healthy animals, showing significantly higher antioxidant performance and lower DNA damage compared with CMV in lung tissue and plasma. Total antioxidant performance showed a significant positive correlation ( r = 0.58; P = 0.0006) in plasma and lung tissue. In addition, comet assay presented a significant positive correlation ( r = 0.66; P = 0.007) between cells recovered from target tissue and peripheral blood. Moreover, antioxidant performance was significantly and negatively correlated with DNA damage ( r = −0.50; P = 0.002) in lung tissue. This study indicates that both TAP and comet assay identify increased oxidative stress in CMV rabbits compared with HFOV. Antioxidant performance analyzed by TAP and oxidative DNA damage by comet assay, both in plasma, reflects oxidative stress in the target tissue, which warrants further studies in humans.

scholarly journals Efficacy and Safety Testing of a COVID-19 Era Emergency Ventilator in a Healthy Rabbit Lung Model

2021 ◽  
Author(s):  
Luke A. White ◽  
Benjamin S. Maxey ◽  
Giovanni F. Solitro ◽  
Hidehiro Takei ◽  
Steven A. Conrad ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Lung Injury ◽  
Blood Gas ◽  
Arterial Blood Gas ◽  
Arterial Partial Pressure ◽  
Arterial Blood ◽  
Emergency Ventilation ◽  
Gas Measurements ◽  
End Tidal ◽  
Spontaneously Breathing

Abstract Background: The COVID-19 pandemic revealed a substantial and unmet need for low-cost, easily accessible mechanical ventilation strategies for use in medical resource-challenged areas. Internationally, several groups developed non-conventional COVID-19 era emergency ventilator strategies as a stopgap measure when conventional ventilators were unavailable. Here, we compared our FALCON emergency ventilator in a rabbit model and compared its safety and functionality to conventional mechanical ventilation. Methods: New Zealand white rabbits (n = 5) received mechanical ventilation from either the FALCON or a conventional mechanical ventilator (Engström CarestationTM) for 1 hour each. Airflow and pressure, blood O2 saturation, end tidal CO2, and arterial blood gas measurements were measured. Additionally, gross and histological lung samples were compared to spontaneously breathing rabbits (n = 3) to assess signs of ventilator induced lung injury.Results: All rabbits were successfully ventilated with the FALCON. At identical ventilator settings, tidal volumes, pressures, and respiratory rates were similar between both ventilators, but the inspiratory to expiratory ratio was lower using the FALCON. End tidal CO2 was significantly higher on the FALCON, and arterial blood gas measurements demonstrated lower arterial partial pressure of O2 at 30 minutes and higher arterial partial pressure of CO2 at 30 and 60 minutes using the FALCON. However, when ventilated at higher respiratory rates, we observed a stepwise decrease in end tidal CO2. Poincaré plot analysis demonstrated small but significant increases in short-term and long-term variation of peak inspiratory pressure generation from the FALCON. Wet to dry lung weight and lung injury scoring between the mechanically ventilated and spontaneously breathing rabbits were similar. Conclusions: Although conventional ventilators are always preferable outside of emergency use, the FALCON ventilator safely and effectively ventilated healthy rabbits without lung injury. Emergency ventilation using accessible and inexpensive strategies like the FALCON may be useful for communities with low access to medical resources and as a backup form of emergency ventilation.

scholarly journals c-Fos is a mechanosensor that regulates inflammatory responses and lung barrier dysfunction during ventilator-induced acute lung injury

2022 ◽  
Vol 22 (1) ◽  
Author(s):  
Leilei Zhou ◽  
Chunju Xue ◽  
Zongyu Chen ◽  
Wenqing Jiang ◽  
Shuang He ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Protein Expression ◽  
Tidal Volume ◽  
Lung Tissue ◽  
Inflammatory Reaction ◽  
Specific Inhibitor ◽  
Control Group ◽  
Fos Protein ◽  
Volume Group

Abstract Background As one of the basic treatments performed in the intensive care unit, mechanical ventilation can cause ventilator-induced acute lung injury (VILI). The typical features of VILI are an uncontrolled inflammatory response and impaired lung barrier function; however, its pathogenesis is not fully understood, and c-Fos protein is activated under mechanical stress. c-Fos/activating protein-1 (AP-1) plays a role by binding to AP-1 within the promoter region, which promotes inflammation and apoptosis. T-5224 is a specific inhibitor of c-Fos/AP-1, that controls the gene expression of many proinflammatory cytokines. This study investigated whether T-5224 attenuates VILI in rats by inhibiting inflammation and apoptosis. Methods The SD rats were divided into six groups: a control group, low tidal volume group, high tidal volume group, DMSO group, T-5224 group (low concentration), and T-5224 group (high concentration). After 3 h, the pathological damage, c-Fos protein expression, inflammatory reaction and apoptosis degree of lung tissue in each group were detected. Results c-Fos protein expression was increased within the lung tissue of VILI rats, and the pathological damage degree, inflammatory reaction and apoptosis in the lung tissue of VILI rats were significantly increased; T-5224 inhibited c-Fos protein expression in lung tissues, and T-5224 inhibit the inflammatory reaction and apoptosis of lung tissue by regulating the Fas/Fasl pathway. Conclusions c-Fos is a regulatory factor during ventilator-induced acute lung injury, and the inhibition of its expression has a protective effect. Which is associated with the antiinflammatory and antiapoptotic effects of T-5224.

scholarly journals Study on the Mechanism of Curcumin Regulating Lung Injury Induced by Outdoor Fine Particulate Matter (PM2.5)

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Kunlun Huang ◽  
ChanMei Shi ◽  
JingQi Min ◽  
Laifu Li ◽  
Tao Zhu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Treatment Group ◽  
Lung Injury ◽  
P38 Mapk ◽  
Lung Tissue ◽  
Inflammatory Responses ◽  
Mapk Pathway ◽  
Intervention Group ◽  
Control Group ◽  
Inflammatory Damage

Background. Epidemiological studies have shown that exposure to PM induces oxidative stress, leading to a variety of health problems. In particular, PM2.5 contains a lot of substances harmful to the human body and penetrates into the lungs to induce lung injury. At the same time, there is increasing evidence that oxidative stress also affects the severity of lung injury. However, there is still no good way to reduce or eliminate these hazards. In the future, more experimental research is needed to further confirm the mechanisms of these hazards and formulate effective preventive measures and treatment plans for their hazard mechanisms. Curcumin has been reported to reduce oxidative stress and inflammatory damage and protect organs. Objective. To investigate whether curcumin can play a protective role against PM2.5-induced oxidative stress and inflammatory damage by inducing expression of the HO-1/CO/P38 MAPK pathway. Methods. In this experiment, PM2.5 was dropped into the trachea to establish a lung injury model in mice. 28 SPF-grade male Kunming mice were randomly divided into 4 groups: normal control group, saline control group, PM2.5 treatment group, and curcumin intervention group. Albumin (ALB), lactate dehydrogenase (LDH), and alkaline phosphatase (ALP) were measured in alveolar lavage fluid (BALF) to assess lung tissue damage. Colorimetric detection of oxidative stress indicators such as MDA, GSH-PX, T-AOC, and CAT in the lung tissue was performed. The levels of IL-6 and TNF-α in the lung tissue were determined by ELISA. Histopathological examination was used for the assessment of alveolar epithelial damage. The protein expression of the HO-1/P38 MAPK pathway in the lung tissue was determined by Western blot and immunohistochemistry. Endogenous CO was detected by spectrophotometry. The results showed that the expression of the HO-1/CO/P38 MAPK protein in the lung tissue was significantly increased in the curcumin intervention group compared with the PM2.5 treatment group, and it was statistically significant (P<0.05). Compared with the PM2.5 treatment group, the curcumin intervention group can reduce the amount of ALB, LDH, and ALP in BALF; reduce the levels of MDA, IL-1, and TNF-α in the lung tissue; and improve GSH-PX, T-AOC, and CAT levels, but there is no statistical difference (P>0.05). Conclusion. We found that PM2.5 can cause lung damage through oxidative stress and inflammatory responses. Oxidative stress and inflammatory responses increase the expression of HO-1/CO/P38 MAPK. The intervention of curcumin can further increase the expression of HO-1/CO/P38 MAPK.

scholarly journals Keratinocyte Growth Factor-2 Is Protective in Oleic Acid-Induced Acute Lung Injury in Rats

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
S. Tenghao ◽  
M. Shenmao ◽  
W. Zhaojun ◽  
B. Jijia ◽  
Z. Wenjie ◽  
...  
Keyword(s):  
Oleic Acid ◽  
Lung Injury ◽  
Lung Tissue ◽  
Evans Blue ◽  
Keratinocyte Growth Factor ◽  
Tunel Assay ◽  
Control Group ◽  
Model Group ◽  
Model Preparation ◽  
Alveolar Capillary

Objective. The aim of this study was to examine the role of keratinocyte growth factor-2 (KGF-2) in oleic acid-induced acute lung injury (ALI) in rats. Methods. Forty-five healthy adult male Sprague Dawley rats were divided into 3 groups. Rat ALI model was established by injection of 0.01 mL/kg oleic acid into the tail vein. Rats in the control group were injected with the same amount of normal saline (NS). In the ALI + KGF-2 group, 5 mg/kg of KGF-2 was instilled into the airway of rats 72 hours before the model preparation, and the control group and the ALI model group were instilled with the same amount of NS. The lung permeability index (LPI) and lung wet/dry weight (W / D) ratios were measured 8 hours after the model preparation. The permeability of pulmonary microvascular endothelium was evaluated by Evans blue leakage test. Histopathological changes were observed under light microscope and the ALI pathology score (LIS) was calculated. Ultrastructural changes of lung tissue were observed under electron microscope. The apoptosis was detected by TUNEL assay. The expression of Claudin-5, ZO-1, and VE Cadherin in lung tissue was qualitatively and quantitatively analyzed by immunohistochemistry, Western Blot, and qRT-PCR, respectively. Results. The ALI model group had severe lung injury and obvious pathological changes, including alveolar septal thickening and inflammatory cell infiltration. TUNEL assay showed that the apoptosis of ALI group was significantly increased. The LIS score, lung W/D ratio, LPI, and Evans blue leakage were significantly higher than those in the control group; electron microscopy showed that the alveolar-capillary barrier was severely damaged in the ALI group. Compared with the control group, the expression of Claudin-5, ZO-1, and VE cadherin in the lung tissue of the ALI model group was significantly attenuated. After pretreatment with KGF-2, the degree of lung tissue damage was significantly reduced and the pathological changes were significantly improved. TUNEL assay showed that the apoptosis of ALI group was decreased. Lung W/D ratio, LPI, and Evans blue leakage decreased; electron microscopy showed that the alveolar-capillary barrier of ALI group recovered significantly. Compared with the ALI model group, the expression of Claudin-5, ZO-1, and VE cadherin in the lung tissue of the KGF-2 pretreatment group increased. Conclusion. The results indicate that KGF-2 may attenuate oleic acid-induced ALI in rats by maintaining the pulmonary microvascular endothelial barrier, which is an effective ALI preventive measure.

scholarly journals High sodium intake during postnatal phases induces an increase in arterial blood pressure in adult rats

2014 ◽  
Vol 112 (12) ◽  
pp. 1923-1932 ◽  
Author(s):  
M. C. S. Moreira ◽  
E. F. da Silva ◽  
L. L. Silveira ◽  
Y. B. de Paiva ◽  
C. H. de Castro ◽  
...  
Keyword(s):  
Sodium Intake ◽  
Tap Water ◽  
Recovery Period ◽  
Control Group ◽  
Adult Rats ◽  
High Sodium ◽  
Arterial Blood ◽  
Hypertension Development ◽  
Lower Magnitude ◽  
Experimental Group

Epigenetic studies suggest that diseases that develop in adulthood are related to certain conditions to which the individual is exposed during the initial stages of life. Experimental evidence has demonstrated that offspring born to mothers maintained on high-Na diets during pregnancy have higher mean arterial pressure (MAP) in adulthood. Although these studies have demonstrated the importance of prenatal phases to hypertension development, no evidence regarding the role of high Na intake during postnatal phases in the development of this pathology has been reported. Therefore, in the present study, the effects of Na overload during childhood on induced water and Na intakes and on cardiovascular parameters in adulthood were evaluated. Experiments were carried out in two groups of 21-d-old rats: experimental group, maintained on hypertonic saline (0·3 m-NaCl) solution and food for 60 d, and control group, maintained on tap water and food. Later, both groups were given water and food for 15 d (recovery period). After the recovery period, chronic cannulation of the right femoral artery was performed in unanaesthetised rats to record baseline MAP and heart rate (HR). The experimental group was found to have increased basal MAP (98·6 (sem 2·6) v. 118·3 (sem 2·7) mmHg, P< 0·05) and HR (365·4 (sem 12·2) v. 398·2 (sem 7·5) beats per min, P< 0·05). There was a decrease in the baroreflex index in the experimental group when compared with that in the control group. A water and Na intake test was performed using furosemide. Na depletion was found to induce an increase in Na intake in both the control and experimental groups (12·1 (sem 0·6) ml and 7·8 (sem 1·1), respectively, P< 0·05); however, this increase was of lower magnitude in the experimental group. These results demonstrate that postnatal Na overload alters behavioural and cardiovascular regulation in adulthood.

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