Increased Susceptibility to Ventilator-associated Lung Injury Persists after Clinical Recovery from Experimental Endotoxemia

2006 ◽  
Vol 104 (1) ◽  
pp. 133-141 ◽  
Author(s):  
Torsten Schreiber ◽  
Lars Hueter ◽  
Konrad Schwarzkopf ◽  
Sylvia Hohlstein ◽  
Barbara Schmidt ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Lung Injury ◽  
Inflammatory Response ◽  
Weight Ratio ◽  
Dry Weight ◽  
Lavage Fluid ◽  
Systemic Injection ◽  
Endotoxin Challenge ◽  
Clinical Recovery ◽  
Increased Susceptibility

Background Endotoxin, when delivered shortly before or during mechanical ventilation, increases susceptibility to ventilation-associated lung injury. However, it is unclear whether increased susceptibility to ventilator-associated lung injury is still present after clinical recovery from a transient endotoxin challenge. Methods Anesthetized rats were submitted to a 4-h period of mechanical ventilation with low (8 ml/kg) or high (24, 27, or 30 ml/kg) tidal volumes (VTs) 24 h after transient illness had been provoked by a single nonlethal intravenous injection of Escherichia coli endotoxin. Control animals were injected with phosphate-buffered saline and underwent the same protocol. Results At 24 h, endotoxin-treated nonventilated animals showed no symptoms of clinical illness, and oxygenation was comparable with that of controls, but lung neutrophil counts were increased. Compared with controls, mechanical ventilation with high VT induced a stronger pulmonary inflammatory response and more severe lung injury in endotoxin-treated animals, as indicated by impaired oxygenation, increased lung wet-to-dry weight ratio, and increased levels of protein, neutrophils, and cytokines in lung lavage fluid. In addition, the highest VT resulted in increased mortality in endotoxin-treated animals. Low VT after endotoxin treatment did not cause functional pulmonary impairment but induced an inflammatory response. Conclusions In this animal model, a 24-h delay after a single systemic injection of endotoxin resulted in clinical recovery and preserved pulmonary function but did not prevent increased susceptibility to ventilator-associated lung injury provoked by high VT. Residual pulmonary inflammation and neutrophilic infiltration at initiation of mechanical ventilation probably contribute to these findings.

scholarly journals Lung injury induced by short-term mechanical ventilation with hyperoxia and its mitigation by deferoxamine in rats

2020 ◽  
Author(s):  
Xiao-Xia Wang ◽  
Xiao-Lan Sha ◽  
Yulan Li ◽  
Chun-Lan Li ◽  
Su-Heng Chen ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Lung Injury ◽  
Weight Ratio ◽  
Dry Weight ◽  
Lavage Fluid ◽  
Tissue Homogenate ◽  
Short Term ◽  
Artery Cannulation ◽  
Short Period ◽  
The Right

Abstract Background: Long-term mechanical ventilation with hyperoxia can induce lung injury. General anesthesia is associated with a very high incidence of hyperoxaemia, despite it usually lasts for a relatively short period of time. It remains unclear whether short-term mechanical ventilation with hyperoxia has an adverse impact on or cause injury to the lungs. The present study aimed to assess whether short-term mechanical ventilation with hyperoxia may cause lung injury in rats and whether deferoxamine (DFO), a ferrous ion chelator, could mitigate such injury to the lungs and explore the possible mechanism. Methods: Twenty-four SD rats were randomly divided into 3 groups (n=8/group): mechanical ventilated with normoxia group (MV group, FiO2=21%), with hyperoxia group (HMV group, FiO2=90%), or with hyperoxia + DFO group (HMV+DFO group, FiO2=90%). Mechanical ventilation under different oxygen concentrations was given for 4 hours.The HMV+DFO group received continuous intravenous infusion of DFO at 200mg•kg-1•d-1, while the MV and HMV groups received an equal volume of normal saline. Carotid artery cannulation was carried out to monitor the blood gas parameters under mechanical ventilation for 2 hours and 4 hours, respectively, and the PaO2/FiO2 ratio was calculated. After 4 hours ventilation, the right anterior lobe of the lung and BALF from the right lung was sampled for pathological and biochemical assays. Results: PaO2 in the HMV and HMV+DFO groups were significantly higher, but the PaO2/FiO2 ratio were significantly lower than those of the MV group (all p<0.01). The lung pathological scores and the wet-to-dry weight ratio (W/D) in the HMV and HMV+DFO groups were significantly higher than those of the MV group, but score and the W/D ratio were reduced by DFO (p<0.05). Biochemically, HMV resulted in significant reductions in SP-C, SP-D, and GR levels and elevation of XOD in both the Bronchoalveolar lavage fluid and the lung tissue homogenate, and all these changes were prevented or significantly reverted by DFO. Conclusions: Mechanical ventilation with hyperoxia for 4 hours induced oxidative injury of the lungs, accompanied by a dramatic reduction in the concentrations of SP-C and SP-D. DFO could mitigate such injury by lowering XOD activity and elevating GR activity.

scholarly journals Ganoderic acid A attenuates lipopolysaccharide-induced lung injury in mice

2019 ◽  
Vol 39 (5) ◽  
Author(s):  
Bing Wan ◽  
Yan Li ◽  
Shuangshuang Sun ◽  
Yang Yang ◽  
Yanling LV ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Mouse Model ◽  
Weight Ratio ◽  
Dry Weight ◽  
Lavage Fluid ◽  
Myeloperoxidase Activity ◽  
Protective Effects ◽  
Ganoderic Acid ◽  
Lower Lung

Abstract The present study aimed to investigate the protective effects of ganoderic acid A (GAA) on lipopolysaccharide (LPS)-induced acute lung injury. In mouse model of LPS-induced acute lung injury, we found that GAA led to significantly lower lung wet-to-dry weight ratio and lung myeloperoxidase activity, and attenuated pathological damages. In addition, GAA increased superoxide dismutase activity, but decreased malondialdehyde content and proinflammatory cytokines levels in the bronchoalveolar lavage fluid. Mechanistically, GAA reduced the activation of Rho/ROCK/NF-κB pathway to inhibit LPS-induced inflammation. In conclusion, our study suggests that GAA attenuates acute lung injury in mouse model via the inhibition of Rho/ROCK/NF-κB pathway.

scholarly journals Anti-Inflammatory Effects of Monoammonium Glycyrrhizinate on Lipopolysaccharide-Induced Acute Lung Injury in Mice through Regulating Nuclear Factor-Kappa B Signaling Pathway

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Xiaoying Huang ◽  
Jiangfeng Tang ◽  
Hui Cai ◽  
Yi Pan ◽  
Yicheng He ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Signaling Pathway ◽  
Interleukin 1 ◽  
Intratracheal Instillation ◽  
Weight Ratio ◽  
Dry Weight ◽  
Inflammatory Cells ◽  
Lavage Fluid ◽  
Therapeutic Mechanism

The present study aimed to investigate the therapeutic effect of monoammonium glycyrrhizinate (MAG) on lipopolysaccharide- (LPS-) induced acute lung injury (ALI) in mice and possible mechanism. Acute lung injury was induced in BALB/c mice by intratracheal instillation of LPS, and MAG was injected intraperitoneally 1 h prior to LPS administration. After ALI, the histopathology of lungs, lung wet/dry weight ratio, protein concentration, and inflammatory cells in the bronchoalveolar lavage fluid (BALF) were determined. The levels of tumor necrosis factor-α(TNF-α) and interleukin-1β(IL-1β) in the BALF were measured by ELISA. The activation of NF-κB p65 and IκB-αof lung homogenate was detected by Western blot. Pretreatment with MAG attenuated lung histopathological damage induced by LPS and decreased lung wet/dry weight ratio and the concentrations of protein in BALF. At the same time, MAG reduced the number of inflammatory cells in lung and inhibited the production of TNF-αand IL-1βin BALF. Furthermore, we demonstrated that MAG suppressed activation of NF-κB signaling pathway induced by LPS in lung. The results suggested that the therapeutic mechanism of MAG on ALI may be attributed to the inhibition of NF-κB signaling pathway. Monoammonium glycyrrhizinate may be a potential therapeutic reagent for ALI.

Diammonium glycyrrhizinate lipid ligand ameliorates lipopolysaccharide-induced acute lung injury by modulating vascular endothelial barrier function

2020 ◽  
Author(s):  
Mei-Mei Liu ◽  
Jin Zhou ◽  
Dan Ji ◽  
Jun Yang ◽  
Yan-Ping Huang ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Pulmonary Edema ◽  
Protein Concentration ◽  
Weight Ratio ◽  
Dry Weight ◽  
Lavage Fluid ◽  
Inhibitory Effect ◽  
Vascular Endothelial ◽  
Junction Protein

Abstract Background: The present study investigated the attenuating effect of diammonium glycyrrhizinate lipid ligand (DGLL) on acute lung injury (ALI) and pulmonary edema induced by lipopolysaccharide (LPS) in rats.Methods: Rat ALI model was established by LPS (10 mg/kg) intraperitoneal injection, and DGLL (30, 60, 120 mg/kg) was administrated orall 1 hour before LPS infusion. Six hours after LPS stimulation, lung injury was evaluated by histological staining. Pulmonary edema was evaluated by lung wet-dry weight ratio, the protein concentration of bronchoalveolar lavage fluid (BALF), and the evans blue (EB) extravasation in lung tissues. The expression of cytokines and adhesion molecules in lung tissues were detected by ELISA method. The myeloperoxidase (MPO) expression was detected by immunohistochemical staining. Western blot was used to detect the expression changes of the proteins associated with pulmonary inflammation and microvascular permeability.Results: DGLL significantly inhibited LPS induced ALI, manifested as attenuation of MPO positive cells and TNF-α, IL-6, ICAM-1 expression in rat lung tissue. In addition, DGLL abrogated LPS-induced pulmonary edema, decreased the protein concentration in BALF and EB extravasation. Meanwhile, DGLL inhibited the degradation of vascular endothelial cadherin (VE-Cadherin) and tight junction protein, including ZO-1, Occludin, and JAM-1.Conclusions: DGLL has an inhibitory effect on LPS-induced rat ALI, which is related to the inhibition of inflammatory cell infiltration and microvascular barrier disruption. These results provide a theoretical basis for DGLL in the potential clinical treatment of ALI.

scholarly journals Role of Alveolar Macrophages in Candida-Induced Acute Lung Injury

2001 ◽  
Vol 8 (6) ◽  
pp. 1258-1262 ◽  
Author(s):  
Yutaka Kubota ◽  
Yoshinobu Iwasaki ◽  
Hidehiko Harada ◽  
Ichiro Yokomura ◽  
Mikio Ueda ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Alveolar Macrophages ◽  
Weight Ratio ◽  
Dry Weight ◽  
Lavage Fluid ◽  
Secretory Cells ◽  
Disseminated Candidiasis ◽  
Cellular Source ◽  
Immunohistochemical Studies

ABSTRACT Recent studies have shown that alveolar macrophages (AMs) not only act as phagocytes but also play a central role as potent secretory cells in various lung diseases, including pneumonia and acute respiratory distress syndrome. The behavior of AMs during disseminated candidiasis, however, is insufficiently elucidated. This study is the first to report disseminated candidiasis in AM-depleted mice and to analyze the effect of AMs on Candida-induced acute lung injury. While all AM-sufficient mice died by day 2 after infection withCandida albicans, no mortality was observed among AM-depleted mice. Unexpectedly, the CFU numbers of C. albicans isolated from the lungs of AM-depleted mice were significantly higher than those for C. albicans isolated from AM-sufficient mice. The lung wet-to-dry weight ratio was lower for AM-depleted mice than for AM-sufficient mice, although this difference was not significant. We found that bronchoalveolar lavage fluid (BALF) from AM-depleted mice in candidemia contained fewer neutrophils than BALF from AM-sufficient mice. In addition, myeloperoxidase activities in lung homogenates of AM-depleted mice were significantly lower than those in homogenates of AM-sufficient mice. A significant decrease in levels of murine macrophage inflammatory protein 2 (MIP-2), a potent chemoattractant for neutrophils, was noted in lung homogenates from AM-depleted mice compared with levels in homogenates from AM-sufficient mice. Immunohistochemical studies using anti-MIP-2 antibodies revealed that AMs were the cellular source of MIP-2 within the lung during candidemia. We observed that AM depletion decreased levels of AM-derived neutrophil chemoattractant, alleviated acute lung injury during candidemia, and prolonged the survival of mice in candidemia, even though clearance of C. albicans from the lungs was reduced.

scholarly journals Lung protective effect of Punicalagin on LPS-induced acute lung injury in mice

2022 ◽  
Author(s):  
Yibin Zeng ◽  
Hongying Zhao ◽  
Tong Zhang ◽  
Chao Zhang ◽  
Yanni He ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Protective Effect ◽  
Lung Tissue ◽  
White Blood Cells ◽  
Weight Ratio ◽  
Dry Weight ◽  
Lavage Fluid ◽  
Protein Levels ◽  
Anti Inflammation

Background: Punicalagin (Pun) is one of the main bioactive compounds in pomegranate peel, it possesses many properties, including antioxidant, anti-inflammation, and immunosuppressive activities. The study was aimed to investigate the protective effect and mechanisms of Pun on lipopolysaccharide (LPS) induced acute lung injury (ALI) in mice. Methods and Results: Forty-eight BALB/c male mice were used to establish ALI by intratracheal-instilled 2.4 mg/kg LPS, the mice were randomly divided into model and Pun (10, 20, 40 mg/kg) groups. The other twelve mice were intratracheal-instilled same volume of water as control. After 2 h of receiving LPS, mice were administrated drug through intraperitoneal injection. Lung index, histopathological changes, white blood cells and biomarkers in bronchoalveolar lavage fluid (BALF) were analyzed. The protein expression of total and phosphor p65, IκBα, ERK1/2, JNK and p38 in lung tissue was detected. The result showed that Pun could reduce the lung index and wet/dry weight ratio, improve lung histopathological injury. In addition, Pun decreased the inflammation cells and regulated the biomarkers in BALF. Furthermore, Pun dose-dependently reduced the phosphor protein levels of p65, IκBα, ERK1/2, JNK and p38 in lung tissue, which exhibited that the effect of Pun related to MAPKs pathway. More importantly, there is no toxicity was observed in the acute toxicity study of Pun. Conclusion: Pun improves LPS-induced ALI mainly through its anti-inflammatory properties, which is associated with NF-κB and MAPKs signaling pathways. The study implied that Pun maybe a potent agent against ALI in future clinic.

scholarly journals Intravenous Dexamethasone Attenuated Inflammation and Influenced Apoptosis of Lung Cells in an Experimental Model of Acute Lung Injury

2016 ◽  
pp. S663-S672 ◽  
Author(s):  
P. KOSUTOVA ◽  
P. MIKOLKA ◽  
S. BALENTOVA ◽  
M. ADAMKOV ◽  
M. KOLOMAZNIK ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Caspase 3 ◽  
Diffuse Alveolar Damage ◽  
Weight Ratio ◽  
Dry Weight ◽  
Inflammatory Cells ◽  
Lavage Fluid ◽  
Lung Edema ◽  
Edema Formation

Acute lung injury (ALI) is characterized by diffuse alveolar damage, inflammation, and transmigration and activation of inflammatory cells. This study evaluated if intravenous dexamethasone can influence lung inflammation and apoptosis in lavage-induced ALI. ALI was induced in rabbits by repetitive saline lung lavage (30 ml/kg, 9±3-times). Animals were divided into 3 groups: ALI without therapy (ALI), ALI treated with dexamethasone i.v. (0.5 mg/kg, Dexamed; ALI+DEX), and healthy non-ventilated controls (Control). After following 5 h of ventilation, ALI animals were overdosed by anesthetics. Total and differential counts of cells in bronchoalveolar lavage fluid (BAL) were estimated. Lung edema was expressed as wet/dry weight ratio. Concentrations of IL-1ß, IL-8, esRAGE, S1PR3 in the lung were analyzed by ELISA methods. In right lung, apoptotic cells were evaluated by TUNEL assay and caspase-3 immunohistochemically. Dexamethasone showed a trend to improve lung functions and histopathological changes, reduced leak of neutrophils (P<0.001) into the lung, decreased concentrations of pro-inflammatory IL-1β (P<0.05) and marker of lung injury esRAGE (P<0.05), lung edema formation (P<0.05), and lung apoptotic index (P<0.01), but increased immunoreactivity of caspase-3 in the lung (P<0.001). Considering the action of dexamethasone on respiratory parameters and lung injury, the results indicate potential of this therapy in ALI.

scholarly journals Agmatine Protects against Zymosan-Induced Acute Lung Injury in Mice by Inhibiting NF-κB-Mediated Inflammatory Response

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Xuanfei Li ◽  
Zheng Liu ◽  
He Jin ◽  
Xia Fan ◽  
Xue Yang ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Lung Inflammation ◽  
Weight Ratio ◽  
Dry Weight ◽  
Lavage Fluid ◽  
Myeloperoxidase Activity ◽  
Beneficial Effects ◽  
Hypoxic Ischemia ◽  
Tnf Α

Acute lung injury (ALI) is characterized by overwhelming lung inflammation and anti-inflammation treatment is proposed to be a therapeutic strategy for ALI. Agmatine, a cationic polyamine formed by decarboxylation of L-arginine, is an endogenous neuromodulator that plays protective roles in diverse central nervous system (CNS) disorders. Consistent with its neuromodulatory and neuroprotective properties, agmatine has been reported to have beneficial effects on depression, anxiety, hypoxic ischemia, Parkinson’s disease, and gastric disorder. In this study, we tested the effect of agmatine on the lung inflammation induced by Zymosan (ZYM) challenge in mice. We found that agmatine treatment relieved ZYM-induced acute lung injury, as evidenced by the reduced histological scores, wet/dry weight ratio, and myeloperoxidase activity in the lung tissue. This was accompanied by reduced levels of TNF-α, IL-1β, and IL-6 in lung and bronchoalveolar lavage fluid and decreased iNOS expression in lung. Furthermore, agmatine inhibited the phosphorylation and degradation of IκB and subsequently blocked the activation of nuclear factor (NF)-κB induced by Zymosan. Taken together, our results showed that agmatine treatment inhibited NF-κB signaling in lungs and protected mice against ALI induced by Zymosan, suggesting agmatine may be a potential safe and effective approach for the treatment of ALI.

scholarly journals MEF2C alleviates acute lung injury in cecal ligation and puncture (CLP)-induced sepsis rats by up-regulating AQP1

2021 ◽  
Vol 49 (5) ◽  
pp. 117-124
Author(s):  
Wenmei Liang ◽  
Li Guo ◽  
Tonghua Liu ◽  
Song Qin
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Inflammatory Response ◽  
Cecal Ligation ◽  
Weight Ratio ◽  
Dry Weight ◽  
Tunel Staining ◽  
Cecal Ligation And Puncture ◽  
Tnf Α ◽  
Factor Α

Background: Sepsis is a systemic inflammatory response syndrome and leads to patient’s death. Objective: To investigate the effect of myocyte enhancer factor 2 (MEF2C) on acute lung injury (ALI) with sepsis and its possible mechanism.Material and Methods: The cecal ligation and puncture (CLP)-induced sepsis rat model was established. The lung injury was determined by lung wet–dry weight ratio, the concentration of inflammatory cytokines, including tumor necrosis factor-α (TNF-α), Interlukin (IL)-6, IL-1β, and IL-10, were measured by the enzyme-linked-immunosorbent serologic assay kit. The cell apoptosis was detected by TUNEL staining assay.Results: Interestingly, MEF2C was down-regulated in this model. Moreover, adeno-associated virus (AAV)-MEF2C treatment markedly suppressed TNF-α, IL-1β, and IL-6 concentrations but promoted IL-10 concentration in serum in CLP-challenged rats. Besides, overexpression of MEF2C alleviates CLP-induced lung injury. Interestingly, AAV-MEF2C treatment was confirmed to suppress apoptosis in CLP-induced sepsis rats as well as promote aquaporin APQ1 expres-sion. Mechanistically, the rescue experiments indicated that MEF2C alleviated CLP-induced lung inflammatory response and apoptosis via up-regulating AQP1.Conclusion: In summary, overexpression of MEF2C suppressed CLP-induced lung inflamma-tory response and apoptosis via up-regulating AQP1, providing a novel therapeutic target for sepsis-induced ALI.

scholarly journals Shuang-Huang-Lian Attenuates Lipopolysaccharide-Induced Acute Lung Injury in Mice Involving Anti-Inflammatory and Antioxidative Activities

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Lei Fang ◽  
Yuan Gao ◽  
Fen Liu ◽  
Rui Hou ◽  
Run-Lan Cai ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Bronchoalveolar Lavage ◽  
Bronchoalveolar Lavage Fluid ◽  
Weight Ratio ◽  
Dry Weight ◽  
Lavage Fluid ◽  
Myeloperoxidase Activity ◽  
Scutellariae Radix ◽  
Anti Inflammatory

Shuang-Huang-Lian (SHL) is a common traditional Chinese preparation extracted fromLonicerae Japonicae Flos, Scutellariae Radix, andFructus Forsythiae. In this study, we demonstrate the anti-inflammatory and antioxidative effects of SHL on lipopolysaccharide- (LPS-) induced acute lung injury (ALI) in mice. SHL reduced the lung wet/dry weight ratio, lowered the number of total cells in the bronchoalveolar lavage fluid, and decreased the myeloperoxidase activity in lung tissues 6 h after LPS treatment. It also inhibited the overproduction of proinflammatory cytokines (TNF-α, IL-1β, and IL-6) in the bronchoalveolar lavage fluid. Histological studies demonstrated that SHL attenuated LPS-induced interstitial edema, hemorrhage, and the infiltration of neutrophils into the lung tissue. Moreover, SHL could also enhance the superoxide dismutase and catalase activities, increase the reduced glutathione content, and decrease the malondialdehyde content. The present results suggest that SHL possesses anti-inflammatory and antioxidative properties that may protect mice against LPS-induced ALI.

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