Degree Of Pulmonary Edema Research Articles

Lung ultrasound in the evaluation of pulmonary edema in newborns with critical congenital heart disease

BackgroundNewborns with critical congenital heart disease (CCHD) with increased pulmonary blood flow (PBF) are at high risk for congestive heart failure. In this study, we aimed to evaluate the presence and degree of pulmonary edema in newborns with CCHD using lung ultrasound (LUS) during the perioperative period. MethodsProspective clinical trial, 44 newborn patients with CCHD were evaluated in this prospective clinical trial. LUS was repeatedly performed to determine the course of pulmonary edema during the perioperative period. LUS was performed simultaneously with chest radiography (CXR), which was the main part of patient management. The primary outcome of this study was to identify whether a correlation existed between LUS and CXR findings. The secondary outcomes were to determine the relationship between LUS and the need for respiratory support, diuretic use, vasoactive inotropic score (VIS), and pro-B-type natriuretic peptide (pro-BNP) levels during the perioperative period. ResultsThe mean gestational age of the patients was 38.3 ± 1.7 weeks, with a mean birth weight of 3026 ± 432 g. In the preoperative period, both LUS and CXR images were consistent with clinical signs of pulmonary edema. On the first postoperative day, pulmonary edema increased compared to the preoperative period but gradually decreased by the 6th day of surgery (p < 0.05). Positive correlations were observed between the LUS and CXR findings at all study points (p < 0.05). The LUS findings exhibited trends parallel to those of VIS, serum pro-BNP levels, need for respiratory support, and diuretic requirements. As expected, these trends were more pronounced in CCHDs where PBF increased. ConclusionIn CCHD, serial lung ultrasound (LUS) assessments, particularly in cases with increased PBF, can provide valuable guidance for managing patients during the perioperative period.

Carnosol alleviates sepsis-induced pulmonary endothelial barrier dysfunction by targeting nuclear factor erythroid2-related factor 2/sirtuin-3 signaling pathway to attenuate oxidative damage.

Excessive reactive oxygen species production during acute lung injury (ALI) will aggravate the inflammatory process and endothelial barrier dysfunction. Carnosol is a natural phenolic diterpene with antioxidant and anti-inflammatory properties, but its role in treating sepsis-induced ALI remains unclear. This study aims to explore the protective effects and underlying mechanisms of carnosol in sepsis-induced ALI. C57BL/6 mouse were preconditioned with carnosol for 1 h, then the model of lipopolysaccharide (LPS)-induced sepsis was established. The degree of pulmonary edema, oxidative stress, and inflammation were detected. Endothelial barrier function was evaluated by apoptosis and cell junctions. In vitro, Mito Tracker Green probe, JC-1 staining, and MitoSOX staining were conducted to investigate the effect of carnosol on mitochondria. Finally, we investigated the role of nuclear factor-erythroid 2-related factor (Nrf2)/sirtuin-3 (SIRT3) in carnosol against ALI. Carnosol alleviated LPS-induced pulmonary oxidative stress and inflammation by inhibiting excess mitochondrial reactive oxygen species production and maintaining mitochondrial homeostasis. Furthermore, carnosol also attenuated LPS-induced endothelial cell barrier damage by reducing vascular endothelial cell apoptosis and restoring occludin, ZO-1, and vascular endothelial-Cadherin expression in vitro and in vivo. In addition, carnosol increased Nrf2 nuclear translocation to promote SIRT3 expression. The protective effects of carnosol on ALI were largely abolished by inhibition of Nrf2/SIRT3. Our study has provided the first evidence that the Nrf2/SIRT3 pathway is a protective target of the endothelial barrier in ALI, and carnosol can serve as a potential therapeutic candidate for ALI by utilizing its ability to target this pathway.

ANXA3 interference inactivates ERK/ELK1 pathway to mitigate inflammation and apoptosis in sepsis-associated acute lung injury

Acute lung injury (ALI) is a prevailing and deadly complication of sepsis coupled with increasing incidence and fatality rate. Annexin A3 (ANXA3) has been unraveled to be upregulated during sepsis. This study purposed to assess the role and the mechanism of ANXA3 in sepsis-induced ALI. After the construction of mouse model of sepsis, the pathological changes of mice lung tissues were estimated by H&E staining. ANXA3 expression in mice lung tissues and serum was examined. The degree of pulmonary edema and the levels of inflammatory factors in bronchoalveolar lavage fluid (BALF) were analyzed. In lipopolysaccharide (LPS)-induced mouse ALI model in vitro, CCK-8 assay measured cell viability and flow cytometry analysis detected cell apoptosis. Besides, ELISA assay detected the release of inflammatory cytokines. Western blot analyzed the expression of proteins associated with inflammation, apoptosis and extracellular-signal-regulated kinase (ERK)/ETS-like gene 1 (ELK1) signaling. Results revealed that ANXA3 was overexpressed in the lung tissues and serum of septic mice. Following the knockdown of ANXA3, sepsis-induced lung injury was alleviated, manifested as reduced lung edema, decreased inflammatory cell infiltration and inhibited cell apoptosis. Additionally, ANXA3 silence blocked ERK/ELK1 signaling both in sepsis mouse models and in vitro model of ALI induced by lipopolysaccharide (LPS). Moreover, the inhibitory effects of ANXA3 silencing on ERK/ELK1 signaling activation, the viability damage, inflammation and apoptosis in LPS-induced mouse ALI model in vitro were partially reversed by ERK activator. Collectively, depletion of ANXA3 exerted suppressive effects on the inflammation and apoptosis in sepsis-induced ALI through blocking ERK/ELK1 signaling.

Studying the possibilities of pharmacological correction of hypoxia-induced pulmonary hypertension using a phenolic compound with a laboratory cypher KUD975

The aim of our work was to study a pharmacological activity of a selective arginase-2 and thrombin inhibitor from a phenolic compounds group with a laboratory cypher KUD975 on a model of arterial pulmonary hypertension induced by hypoxia.Materials and methods. To simulate pulmonary hypertension (РН), animals were placed in a normobaric hypoxic chamber and subjected to 5 weeks of hypoxia with an oxygen content of 10% in the air. After 3 weeks of hypoxia, the animals were administered with the test compound KUD975 (intragastrically, at a dose of 2 mg/kg once a day for 2 weeks). L-norvaline (intragastrically, 20 mg/kg) was used as a reference drug. To assess the development and correction of РН, measurements of cardiohemodynamics, analysis of blood gas composition, study of the number of circulating endothelial precursor cells (EPCs), quantitative PCR assessing the expression of mRNA VEGF-R2, SGF-1 (stromal growth factor-1) and MCP-1 (monocyte chemoattractant protein-1). Next, a histological examination of the lungs and heart was performed, the degree of pulmonary edema and the concentration of cardiotrophin-1 and atrial natriuretic peptide were assessed.Results. The administration of the studied phenolic compound with laboratory cypher KUD975, as well as the reference drug L-norvaline, led to a decrease in the right ventricular systolic pressure against the background of modeling РН. The present study shows a more than twice-fold decrease in the number of circulating (EPCs) in the animals group with modeling a hypoxia-induced circulatory РН (171.3±12.1) in comparison with the group of intact animals (296.1±31.7; p=0.0018). The recovery of EPCs was noted in the animals group administered with KUD-975 and L-norvaline, up to 247.5±34.2 (p=0.0009 compared with a pulmonary arterial hypertension (PAH) and 235.6±36.4 (p=0.008 compared to PAH), respectively. The studied compounds had a protective effect by statistically significantly increasing the expression of VEGF-R2 mRNA and decreasing the expression of SGF-1 mRNA, reducing the lung moisture coefficient and the concentrations of cardiotrophin-1 and atrial natriuretic peptide and preventing vascular remodeling caused by hypoxia.Conclusion. When studying the pharmacological activity, it was shown that the phenolic compound with the laboratory cypher KUD975 normalizes hemodynamic parameters, reduces the signs of remodeling of the heart and pulmonary vessels and has a pronounced endothelial protective effect on the model of hypoxia-induced РН, and is superior to the activity of the reference drug L-norvaline.

Pachymic acid ameliorates bleomycin-induced pulmonary fibrosis through inhibiting endoplasmic reticulum stress in rats.

The effect of pachymic acid (PA) on pulmonary fibrosis in rats was expected to be investigated in this study. Firstly, bleomycin (BLM) was used to establish pulmonary fibrosis rat model, then PA (10, 20, or 40 mg/kg) was intragastrically administered to the rats for 14 days. Subsequently, a variety of tests was performed to observe changes in sample tissues after different treatments. Briefly, the degree of pulmonary edema in rats was assessed through dry/wet weight ratio. Hematoxylin and eosin (H&E) staining and Masson's trichrome staining were used to observe the pathological injury and fibrosis of lung tissue. Biochemical kits were applied to measure the levels of hydroxyproline (Hyp), transforming growth factor beta-1 (TGFβ-1), malondialdehyde (MDA), reactive oxygen species (ROS), and adenosine triphosphate (ATP) and the activities of superoxide dismutase (SOD) and catalase (CAT) in rat lung tissues of each group. The mitochondrial DNA (mtDNA) copy number in rat lung tissue was tested using qRT-PCR. Additionally, the western blot was employed to detect the expression levels of pulmonary fibrosis-related proteins and endoplasmic reticulum (ER) stress-related proteins in each group of rat lung tissue. By virtue of experimental verification above, PA was discovered to alleviate BLM-induced pulmonary edema, pulmonary fibrosis and histopathological damage. On the one hand, PA treatment decreased Hyp and TGF-β1 levels and down-regulated pulmonary fibrosis-related protein expression [collagen I, α-smooth muscle actin (α-SMA), and fibronectin] in the lung tissue of BLM rats. On the other hand, it significantly increased the levels of SOD, CAT and ATP while decreased the activities of MDA and ROS in BLM rat lung tissues. In addition, the expression levels of ER stress-related proteins [glucose-regulated protein 78 (GRP78), C/EBP homologous protein (CHOP), Caspase 9, and activating transcription factor 4 (ATF4)] were significantly down-regulated in the lung tissue of BLM rats after PA treatment. Collectively, PA may ameliorate BLM-induced pulmonary fibrosis and histopathological damage in rats through inhibiting ER stress and improving mitochondrial function.

Feasibility and safety of 1-min sit-to-stand test in acute decompensated heart failure confirmed by lung ultrasound.

This study innovatively proposed the 1-min sit-to-stand test (1-min STST) as an assessment tool for functional capacity in acute decompensated heart failure (ADHF), in which its feasibility and safety were investigated. This was a prospective, single-center cohort study. The 1-min STST was performed after the first 48 h of admission when vital signs and Borg score were collected. Lung ultrasound was used to measure pulmonary edema by B-lines before and after the test. Seventy-five patients were enrolled in the study, of whom 40% were in functional class IV on admission. The mean age was 58.3 ± 15.7 years and 40% of the patients were male. 95% patients accomplished the test and the average number of repetitions was 18 ± 7. No adverse event was recorded during or after the 1-min STST. Blood pressure, heart rate, and degree of dyspnea were increased after the test (all p < 0.001), while oxygen saturation was slightly decreased (97.0 ± 1.6 vs. 96.3 ± 2.0%, p = 0.003). The degree of pulmonary edema (χ2 = 8.300, p = 0.081) was not significantly changed, while there was a reduction in the absolute number of B-lines [9 (3, 16) vs. 7 (3, 13), p = 0.008]. The application of the 1-min STST in early stage of ADHF appeared to be safe and feasible, which induce neither adverse event nor pulmonary edema. It may serve as a new tool of functional capacity assessment, as well as a reference of exercise rehabilitation.

Sophoridine inhibits endotoxin-induced acute lung injury by enhancing autophagy of macrophage and reducing inflammation.

Acute lung injury (ALI) is characterized by uncontrolled inflammation, which can lead to respiratory distress syndrome and cause patient death. In this study, we sought to determine the role of sophoridine, a compound purified from sophora, in ALI. A mouse model of ALI was established by treating mice with LPS through nonexposed tracheal instillation. After LPS-induced mice were treated with sophoridine, LPS-induced alveolar wall thickening, alveolar interstitial inflammatory exudation and thickening, and the degree of pulmonary edema were found to be inhibited. Macrophages play an important role in inflammation, and in vitro experiments have demonstrated that sophoridine reduces the LPS-induced expression of inflammatory factors by macrophages, suggesting that sophoridine may inhibit lung inflammation in LPS-treated mice through reduces the secretion of inflammatory factors. Further, treatment with sophoridine up-regulated autophagy in macrophage cells in vitro and mouse lung tissues in vivo. LPS can bind to TLRs and activate the MyD88/NF-κB pathways, leading to increased inflammation in the pathogenesis of ALI. Our findings revealed that sophoridine down-regulated the expression of TLR4/MyD88/NF-κB and mTOR mRNA and protein in mouse pulmonary tissue. Collectively, these findings indicate that sophoridine may inhibit LPS-induced ALI by enhancing autophagy of macrophages and reducing inflammation.

Biochanin A as an α-hemolysin inhibitor for combating methicillin-resistant Staphylococcus aureus infection.

Methicillin-resistant Staphylococcus aureus (MRSA) is a multidrug-resistant pathogen that poses a significant risk to global health today. In S. aureus, α-hemolysin is an important virulence factor as it contributes to the capacity of the bacteria to infect the host. Here, we showed that biochanin A (bioA), an isoflavone present in red clover, cabbage and alfalfa, effectively inhibited hemolytic activity at a dose as low as 32μg/mL. Further, western blot and RT-qPCR data showed that bioA reduced the production and expression of MRSA hemolysin in a dose-dependent manner. In addition, when different concentrations of bioA were added to a coculture system of A549 cells and S. aureus, it could significantly decrease cell injury. Importantly, the in vivo study showed that bioA could protect mice from pneumonia caused by a lethal dose of MRSA, as evidenced by improving their survival and reducing the number of bacterial colonies in lung tissues, the secretion of hemolysin into alveolar lavage fluid and the degree of pulmonary edema. In conclusion, biochanin A protected the host from MRSA infection by inhibiting the expression of the hemolysin of MRSA, which may provide experimental evidence for its development to a potential anti-MRSA drug.

The Elk1/MMP-9 axis regulates E-cadherin and occludin in ventilator-induced lung injury

BackgroundVentilator-induced lung injury (VILI) is a common complication in the treatment of respiratory diseases with high morbidity and mortality. ETS-domain containing protein (Elk1) and Matrix metalloproteinase (MMP) 9 are involved in VILI, but the roles have not been fully elucidated. This study examined the mechanisms of the activation of MMP-9 and Elk1 regulating barrier function in VILI in vitro and in vivo.MethodsFor the in vitro study, Mouse lung epithelial cells (MLE-12) were pre-treated with Elk1 siRNA or MMP-9 siRNA for 48 h prior to cyclic stretch at 20% for 4 h. For the in vivo study, C57BL/6 mice were pre-treated with Elk1 siRNA or MMP-9 siRNA for 72 h prior to 4 h of mechanical ventilation. The expressions of Elk1, MMP-9, Tissue inhibitor of metalloproteinase 1 (TIMP-1), E-cadherin, and occludin were measured by Western blotting. The intracellular distribution of E-cadherin and occludin was shown by immunofluorescence. The degree of pulmonary edema and lung injury were evaluated by Hematoxylin–eosin (HE) staining, lung injury scores, Wet/Dry (W/D) weight ratio, total cell counts, and Evans blue dye.Results20% cyclic stretch and high tidal volume increases the expressions of Elk1, MMP-9, and TIMP-1, increases the ratio of MMP-9/TIMP-1, decreases the E-cadherin and occludin level. Elk1 siRNA or MMP-9 siRNA reverses the degradations of E-cadherin, occludin, and the ratio of MMP-9/TIMP-1 caused by cyclic stretch. Elk1 siRNA decreases the MMP-9 level with or not 20% cyclic stretch and high tidal volume.ConclusionsThe results demonstrate mechanical stretch damages the tight junctions and aggravates the permeability in VILI, Elk1 plays an important role in affecting the tight junctions and permeability by regulating the balance of MMP-9 and TIMP-1, thus indicating the therapeutic potential of Elk1 to treat VILI.

Evaluation of extravascular lung water in patients with acute respiratory distress syndrome by syndecan-1 combined with lung ultrasonography

To investigate the value of plasma syndecan-1 (SDC-1) combined with lung ultrasonography in evaluating the degree of extravascular lung water in patients with acute respiratory distress syndrome (ARDS). From July 2018 to July 2019, 50 patients with ARDS admitted to the department of intensive care unit of Wuxi People's Hospital Affiliated to Nanjing Medical University were enrolled. After admission, pulse indicator continuous cardiac output (PiCCO) catheter was established for all patients. PiCCO indexes, including extravascular lung water index (EVLWI) and pulmonary vascular permeability index (PVPI) were monitored by one doctor. Another doctor performed lung ultrasound examination, and calculated the sum of the number of B-lines under 10 ultrasound sections of upper blue point, lower blue point, diaphragm point, Plaps point and rear blue point of both lungs. Then the level of plasma SDC-1 was detected by enzyme linked immunosorbent assay (ELISA). Pearson correlation method was used to analyze the correlation between the number of ultrasonic B-lines, plasma SDC-1 level and EVLWI and PVPI. Taking 10 mL/kg EVLWI as the boundary value, the degree of pulmonary edema in patients with ARDS was divided into mild pulmonary edema and severe pulmonary edema. The receiver operator characteristic curve (ROC curve) was drawn, and the number of B-lines, SDC-1 and the predictive value of the combination of the above two indicators on the severity of pulmonary edema in patients with ARDS were analyzed. The cardiac index (CI) and central venous pressure (CVP) of 50 patients with ARDS were (46.84±6.00) mL×s-1×m-2 and (8.12±1.80) mmHg (1 mmHg = 0.133 kPa), cardiogenic pulmonary edema was excluded. In 50 patients with ARDS, EVLWI was (10.82±2.92) mL/kg, PVPI was 3.02±0.69, the number of ultrasound B-lines was 40.90±13.05, and plasma SDC-1 was (568.25±118.14) μg/L. Pearson correlation analysis showed that the number of ultrasound B-lines in patients with ARDS was significantly positively correlated with EVLWI and PVPI (r1 = 0.802, r2 = 0.799, both P < 0.01). Plasma SDC-1 was also positively correlated with EVLWI and PVPI (r1 = 0.732, r2 = 0.576, both P < 0.01). ROC curve analysis showed that the number of B-lines and SDC-1 had good predictive value for the severity of pulmonary edema in patients with ARDS. The area under ROC curve (AUC) and 95% confidence interval (95%CI) were 0.891 (0.803-0.979) and 0.875 (0.772-0.978), respectively. When the cut-off of B-lines was 40.50, the sensitivity and specificity were 82.1% and 86.4%, respectively. When the cut-off of SDC-1 was 559.37 μg/L, the sensitivity and specificity were 85.7% and 81.8%, respectively. Combining the number of B-lines with SDC-1 could further improve the predictive value of pulmonary water in patients with ARDS. The AUC (95%CI) was 0.958 (0.890-1.000), and the sensitivity and specificity were 92.9% and 91.8%, respectively. The level of plasma SDC-1 and the number of pulmonary ultrasonic B-lines have a good correlation with the degree of extravascular lung water in patients with ARDS. The combined application of the two noninvasive indexes can be used to evaluate the degree of extravascular lung water in patients with ARDS.

Effects of over-expressing heat shock protein 60 on marrow mesenchymal stem cells in the treatment of phosgene-induced acute lung injury

Objective: To investigate the effect of heat shock protein 60 (HSP60) overexpression on the ability of bone marrow mesenchymal stem cells (MSCs) and its therapeutic effect on rats with phosgene induced acute lung injury. Methods: HSP60 was transfected into MSCs by adenovirus. Western blot was used to measure the expressions of HSP60 before and after transfection. CCK-8 assay was used to detect the activity of MSCs, flow cytometry was used to detect the apoptotic ability of MSCs, and Transwell assay was used to observe the migration ability of MSCs. Sixty SPF grade male SD rats were randomly divided into control group, phosgene exposure group (inhalation of phosgene for 5 min) , MSCs group (phosgene exposure, MSCs treatment group) and transfected MSCs group (phosgene exposure, overexpression of HSP60 MSCs treatment group) . The pathological changes of lung were observed by lung pathological section, lung wet dry ratio, the degree of pulmonary edema, the total cell count and total protein content of alveolar lavage fluid, the inflammatory changes of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in BALF and serum were observed. The data were analyzed by Graphpad Prism 8.0 software. Paired comparisons were performed by non paired t-test. One way ANOVA was used for comparison between groups. Results: The proliferation ability of MSCs transfected with HSP60[A= (0.69±0.05) ] was significantly higher than that of MSCs not transfected with HSP60[A= (0.27±0.02) ] (P<0.05) . Compared with the phosgene exposure group, the pulmonary edema and inflammatory factor infiltration of MSCs group and MSCs transfected group were reduced. However, compared with MSCs group, the degree of pulmonary edema in MSCs transfected group was significantly improved, the levels of inflammatory factors IL-6 and TNF-α were significantly decreased, and the total protein content and total cell count in bronchoalveolar lavage fluid were less (P<0.05) . Conclusion: MSCs transfected with HSP60 can enhance the ability of proliferation, anti apoptosis, migration and the curative effect in rats with phosgene induced acute lung injury.

THE MORPHOLOGY OF THE LUNGS AT THE EXPERIMENTAL ACUTE INJURY AND ITS PHARMACOCORRECTION

The study of lung morphology under the influence of various environmental factors is of great interest for various areas of medicine and biology. The study of pathological changes in the respiratory part of the lung of rats with aspiration acute injury and the action of pharmacological correction was carried out. Acetone was used as a damaging agent, and HyperHAES was used as a means of pharmacological correction, containing 7.2% NaCl solution in combination with 6% hydroxyethyl starch, as well as a liposomal form of N-acetylcysteine, which was administered to experimental animals once intravenously after induction of acute lung injury. The control group of animals received antibiotic therapy. The staining of the slides was carried out using hematoxylin and eosin. A quantitative assessment of the histological signs of lung tissue damage was carried out. As a result of the study of preparations of the lungs, the degree of pulmonary edema was established, as well as the anti-edema effect of pharmacological corrections. On the 6th day of the experiment, the anti-edematous effect was retained only after the introduction of N-acetylcysteine. Histological examination of the lungs showed generalized destruction of the organ architectonics in response to the impact of a damaging factor and its reduction under the influence of pharmacological corrections. In the control group, the signs of acute lung injury were most extensive. One day after the administration of the HyperHAEC solution, there were no hemorrhages in the histological picture of the lungs. In a quantitative assessment of the histological signs of acute lung injury, it was shown that the maximum positive effect from the administration of HyperHAES develops 24 hours after application. N-acetylcysteine primarily led to a decrease in leukocyte infiltration and prevented the development of a suppurative process. The lung-protective effect of N-acetylcysteine was realized in 24 hours from the moment of administration and persisted until the 6th day of the experiment. The use of pharmacological correction agents in acute lung injury was reflected in the picture of the lethality of the experimental animals. When HyperHAES was applied, 37.5% of animals died by day 6, in the group with N-acetylcysteine - 28.6%, while in the control group all animals died.

Protective Effect of Piceatannol Against Acute Lung Injury Through Protecting the Integrity of Air-Blood Barrier and Modulating the TLR4/NF-κB Signaling Pathway Activation.

Acute lung injury (ALI) is a common and complex inflammatory lung syndrome with higher morbidity and mortality rate. Piceatannol (PIC) has anti-inflammation and anti-oxidant properties. The study was designed to explore the effect and the action mechanisms of PIC on lipopolysaccharide (LPS)-induced ALI. Twenty-four hours after LPS challenge, mice from different treatment groups were euthanized, and the bronchoalveolar lavage fluid (BALF) and lung tissue samples were collected. Then the degree of pulmonary edema, lung pathological changes, myeloperoxidase (MPO) activity, and the production of pro-inflammatory cytokines were detected. Additionally, the messenger RNA (mRNA) expressions associated with cell adhesion molecules and tight junction were analyzed through quantitative real-time (qRT)-PCR, and the TLR4/NF-κB activation was examined by western blot. The results showed that PIC significantly inhibited LPS-induced lung edema, histopathological damage, MPO activity, cell infiltration, and pro-inflammatory cytokines production. Moreover, PIC notably suppressed mRNA expressions associated with inflammation and cell adhesion molecules. Furthermore, PIC also alleviated LPS-induced damage of air-blood barrier through reducing the levels of total proteins in BALF and recovering the expression of occludin and ZO-1 in the lung tissues. We also found that PIC remarkably restrained the LPS-induced TLR4/NF-κB pathway activation in lung tissues. In conclusion, PIC may be potential to treat LPS-induced acute lung injury (ALI) via regulating air-blood barrier and TLR4/NF-κB signaling pathway activation.

Mechanism of Cxc Chemokine Ligand 5 (CXCL5)/Cxc Chemokine Receptor 2 (CXCR2) Bio-Axis in Mice with Acute Respiratory Distress Syndrome.

BackgroundAcute respiratory distress syndrome (ARDS) is a common acute and severe disease in clinic. Recent studies indicated that Cxc chemokine ligand 5 (CXCL5), an inflammatory chemokine, was associated with tumorigenesis. The present study investigated the role of the CXCL5/Cxc chemokine receptor 2 (CXCR2) bio-axis in ARDS, and explored the underlying molecular mechanism.Material/MethodsThe pathological morphology of lung tissue and degree of pulmonary edema were assessed by hematoxylin-eosin staining and pulmonary edema score, respectively. Real-time PCR and Western blot analysis were performed to detect the expression levels of CXCL5, CXCR2, Matrix metalloproteinases 2 (MMP2), and Matrix metalloproteinases 9 (MMP9) in lung tissues. Enzyme-linked immunosorbent assay (ELISA) was performed to determine the expression levels of CXCL5 and inflammatory factors (IL-1β, IL-6, TNF-α, and IL-10) in serum.ResultsThe results demonstrated that diffuse alveolar damage and pulmonary edema appeared in lipopolysaccharide (LPS)-induced ARDS and were positively correlated with the severity of ARDS. In addition, CXCL5 and its receptor CXCR2 were overexpressed by upregulation of MMP2 and MMP9 in lung tissues of ARDS. In addition, CXCL5 neutralizing antibody effectively alleviated inflammatory response, diffuse alveolar damage, and pulmonary edema, and decreased the expression levels of MMP2 and MMP9 compared to LPS-induced ARDS.ConclusionsWe found that CXCL5/CXCR2 accelerated the progression of ARDS, partly by upregulation of MMP2 and MMP9 in lung tissues with the release of inflammatory factors.

The role of erlotinib in the acute lung injury and the expression of surfactant protein A

Objective To investigate the role of erlotinib in the expression of surfactant protein A (SP-A) in LPS-induced acute lung injury (ALI) of mice model. Methods C57BL/6 mice were randomly (random number)divided into control group (n=6), ER group (n=6), LPS group (n=6), and ER+LPS group (n=6). In the LPS group, 2 mg/kg LPS was instilled into trachea of mice to induce lung injury. In control group, normal saline was instilled into trachea of mice instead. In the ER+LPS group and ER group, 100 mg/kg of erlotinib was instilled into stomach of mice, and one hour later, 2 mg/kg LPS was instilled into trachea of mice in ER+PLS group to induce lung injury. Twenty-four hours later, bronchoalveolar lavage fluid (BALF) and lung tissue of mice in four groups were collected. HE staining were used for evaluating pathological changes of lung injury. Lung wet/dry weight ratio, protein concentrations and total cell numbers in the BALF were measured to determine the degree of pulmonary edema. Immunohistochemical staining and Western Blot were used for testing the protein expression of SP-A, Data of multiple groups were analyzed by one way variance (ANOVA) and inter-group comparisons were made by the least significant difference (LSD) tests. Results There was no significant difference in lung injury score (LIS) between control group (0.056±0.008) and ER (0.064±0.037) group, The LIS in LPS group (0.846±0.047) was higher than that in control group, however the LIS in ER+LPS group (0.279±0.020) was significant lower than that in LPS group (P < 0.05). Lung wet/dry weight, SP-A concentration and total cell numbers in the bronchoalveolar lavage fluid revealed that the degree of pulmonary edema in LPS group was higher than that in control group, and this pulmonary edema was reversed by erlotinib treatment. Immunohistochemical staining and Western blot showed that the expression of SP-A in LPS group was decreased compared with control group, but it was recovered after erlotinib treatment (P < 0.05). Conclusions Erlotinib could protect the LPS-induced ALI, and it may be related to the regulation of SP-A. Key words: Acute lung injury; Mice; Lipopolysaccharide; Erlotinib; Alveolar epithelial cells; Surfactant protein A; Inflammatory response; Epidermal growth factor receptor; Drug treatment

Correlation between controlled lung collapse and early lung injury in dogs.

A new type of pulmonary sequestration ventilator was used to compare the relationship between controlled lung collapse and early lung injury in thoracic surgery for dogs. Eighteen experimental dogs were randomly divided into three groups (G1-G3 groups). After general anesthesia, the shunt balance in lung was controlled and the pulmonary sequestration tube was placed in the femoral artery and vein, and the Swan-Ganz tube was placed into the right internal jugular vein as well. Two-lung ventilation (TLV) was first performed for 20 min, followed by one-lung ventilation (OLV). The degree of collapse was 100% (G1), 90% (G2), and 50% (G3). Blood samples were extracted from femoral artery and jugular vein prior to collapse (T0), and at 30 (T1), 60 (T2), and 120 (T3) min after collapse for blood gas analysis to determine the shunt ratio (Qs/Qt). Blood samples were also subjected to enzyme linked immunosorbent assay (ELISA) to determine serum tumor necrosis factor-α (TNF-α), intercellular immune adhesion molecule-1 (ICAM-1) and interleukin-6 (IL-6) levels. Arterial blood pressure, heart rate, pulmonary artery pressure and other physiological indicators were monitored during the experiment. Lung tissues were collected at T3 to calculate the wet/dry weight ratio (W/D). Histopathological changes were observed and compared by microscopic observation and blind scoring of pathological section after hematoxylin and eosin (H&E) staining. There were no significant differences in the physiological indexes between the two groups during TLV (P>0.05). Mean pulmonary arterial pressure (MPAP) in G2 and G3 groups was significantly more stable than that in G1 group after OLV (P<0.05); shunt ratio Qs/Qt, W/D, and serum TNF-α, ICAM-1 and IL-6 levels in the lung were decreased; and the degrees of pulmonary edema, hemorrhage, inflammatory cell infiltration and lung injury were also decreased. There was no statistically significant difference in each index at each time-point between G2 and G3 groups (P>0.05). Compared with complete lung collapse (collapse degree: 100%), controlled lung collapse (collapse degree: 90% and 50%) can better reduce the intraoperative lung injury, but there was no significant difference between the collapse degrees of 90 and 50%.

Hydrogen gas inhalation during ex vivo lung perfusion of donor lungs recovered after cardiac death.

Ex vivo lung perfusion (EVLP) is a system that circulates normothermic perfusate into procured lungs, allowing for improved lung function and lung assessment. We investigated whether ventilation with hydrogen gas during EVLP improves the donation after cardiac death lung function and whether this effect persists after actual transplantation. Ten pigs were randomly divided into a control group (n = 5) and a hydrogen group (n = 5). No treatment was administered to induce warm ischemic injury for 1 hour after cardiac arrest, and EVLP was applied in procured lungs for 4 hours. During EVLP, the control group was given room air for respiration, and the hydrogen group was given 2% hydrogen gas. After EVLP, the left lung graft was orthotopically transplanted into the recipient and reperfused for 3 hours. During EVLP and reperfusion, the functional parameters and arterial blood gas analysis (ABGA) were measured every hour. Superoxide dismutase, heme oxygenase, interleukin (IL)-6, IL-10, tumor necrosis factor-α, and nucleotide-binding oligomerization domain-like receptor protein 3 were evaluated in lung tissue after reperfusion. Pathologic evaluations were performed, and the degree of apoptosis was evaluated. The wet/dry ratio was measured. During EVLP and reperfusion, functional parameters and ABGA results were better in the hydrogen group. The expressions of superoxide dismutase (p = 0.022) and heme oxygenase-1 (p = 0.047) were significantly higher in the hydrogen group. The expressions of IL-6 (p = 0.024) and nucleotide-binding oligomerization domain-like receptor protein 3 (p = 0.042) were higher in the control group, but IL-10 (p = 0.037) was higher in the hydrogen group. The lung injury severity score and the number of apoptotic cells were higher and the degree of pulmonary edema was more severe in the control group than in the hydrogen group. Hydrogen gas inhalation during EVLP improved donation after cardiac death lung function via reduction of inflammation and apoptosis, and this effect persisted after LTx.

Application progress of conservative fluid therapy in pediatric acute respiratory distress syndrome

Pediatric acute respiratory distress syndrome(PARDS) is one of the most challenging and severe illness in PICU.Proper liquid treatment can reduce the degree of pulmonary edema in patients, improve oxygenation, decrease duration of mechanical ventilation and so on.In this article, we reviewed recent studies on the relationship between fluid overload and clinical effect and conservative fluid therapy, to provide guidances for the selection of optimal treatment of restrictive fluid therapy for PARDS and the direction of the next related research. Key words: Children; Acute respiratory distress syndrome; Fluid overload; Conservative fluid therapy

Protective Effects of Chymostatin on Paraquat-Induced Acute Lung Injury in Mice.

This study aims to evaluate the role of chymostatin in paraquat-induced acute lung injury. Institute of Cancer Research mice were randomly distributed into the NS, DMSO, chymostatin, paraquat or chymostatin treatment groups. Six mice from each group were intraperitoneally injected with chloral hydrate at 0, 1, 2, 4, 8, 12, 24 and 48h after treatment administration. Blood samples were collected through cardiac puncture. Lung tissues were stained with haematoxylin and eosin for the observation of lung histology. The degree of pulmonary oedema was determined on the basis of lung wet-to-dry ratio (W/D). The serum activity of cathepsin G was determined through substrate fluorescence assay. The serum levels of endothelial cell-specific molecule-1 (endocan), tumour necrosis factor-a (TNF-a), interleukin-1β (IL-1β), IL-6 and high-mobility group box protein 1 (HMGB1) were determined through enzyme-linked immunosorbent assay. The expression levels of endocan and nuclear NF-κBp65 in the lung were quantified through Western blot. Chymostatin alleviated the pathological changes associated with acute alveolitis in mice; decreased the lung W/D ratio, the activity of cathepsin G and the serum concentrations of TNF-a, IL-1β, IL-6 and HMGB1; and increased the serum concentration of endocan. Western blot results revealed that chymostatin up-regulated endocan expression and down-regulated nuclear NF-κBp65 expression in the lung. Chymostatin reversed the inflammatory effects of paraquat-induced lung injury by inhibiting cathepsin G activity to up-regulate endocan expression and indirectly inhibit NF-κBp65 activity.

Application of lung ultrasound examination in severe high altitude pulmonary edema

To investigate the application value of lung ultrasonic on severe high altitude pulmonary edema. A prospective, single-blind, case-control study was conducted. Sixty patients with severe high altitude pulmonary edema admitted to Qinghai University Affiliated Hospital from February 2015 to May 2017 were enrolled. The patients were divided into 2 500-3 000 m group, 3 000-3 500 m group and 3 500-4 200 m group according to different altitudes,with 20 patients in each group. The acute physiology and chronic health evaluation II (APACHE II) score was recorded before and 12 hours and 24 hours after treatment. The arterial partial pressure of oxygen (PaO2) was determined by blood gas analysis, and the oxygenation index (PaO2/FiO2) was calculated. Bedside ultrasound scanning was used to determine B line number and pulmonary artery pressure (PAP), and B line score was calculated to reflect lung water content. The correlation between B line score and PaO2/FiO2, PAP and APACHE II scores at each time point was analyzed by Pearson correlation analysis. None of 60 patients died or exited, all of them were enrolled in the final analysis. There was no significant difference in PaO2/FiO2, PAP, APACHE II score or B line score among different altitudes groups (all P > 0.05). Repeated measurement variance analysis showed that the effects of different altitudes on PaO2/FiO2, PAP, APACHE II score and B line score were not statistically significant (F value was 0.312, 0.014, 1.098, 0.236, and P value was 0.340, 0.791, 0.733, and 0.986, respectively). The PaO2/FiO2, PAP, APACHE II score and B line score in all groups were improved obviously from 12 hours after treatment, and the improvements at 24 hours were more than those at 12 hours (all P < 0.05). Repeated measurement variance analysis showed that the effect at different time points on PaO2/FiO2, PAP, APACHE II score and B line score was statistically significant (F value was 1 844.270, 121.690, 1 173.175, 19 426.968, all P < 0.001). The interaction effects of different altitudes and different time points on PaO2/FiO2, PAP, APACHE II score and B line score were not statistically significant (F value was 0.304, 0.404, 1.172, 1.403, and P value was 0.875, 0.805, 0.327, and 0.591, respectively). Pearson correlation analysis showed that there was a significant negative correlation between B line score and PaO2/FiO2 before and after treatment (r value was -0.579, -0.522, and -0.386, all P < 0.01), indicating that the more the B line, the more severe the pulmonary edema, and the worse the oxygenation; with the decrease in B line after treatment, the pulmonary edema was gradually alleviated, and oxygenation was gradually improved. There was a significant positive correlation between B line score and APACHE II score before and 24 hours after treatment (r value was 0.484 and 0.536, both P < 0.01), indicating that the more the B line, the more severe the patient; with the decrease in B line after treatment, the patient's condition improved after treatment. There was only a weak correlation between B line score and PAP at 24 hours after treatment (r = 0.317, P = 0.014), indicating that PAP was not a sensitive indicator in the degree of pulmonary edema in patients. The more the B line in patients with severe high altitude pulmonary edema, the more severe of the pulmonary edema, and the more severe of the patient. There was no significant correlation between the B line score and PAP. Pulmonary ultrasonography can still be used not only in the plain and low elevation areas, but in the high altitude areas, as a reliable method to evaluate the severity of pulmonary edema.