scholarly journals Fluid restriction reduces pulmonary edema in a model of acute lung injury in mechanically ventilated rats

PLoS ONE ◽  
2019 ◽  
Vol 14 (1) ◽  
pp. e0210172 ◽  
Author(s):  
Sarah A. Ingelse ◽  
Jenny Juschten ◽  
Martinus A. W. Maas ◽  
Gustavo Matute-Bello ◽  
Nicole P. Juffermans ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Pulmonary Edema ◽  
Fluid Restriction ◽  
Mechanically Ventilated

scholarly journals Dexmedetomidine alleviates pulmonary edema through the epithelial sodium channel (ENaC) via the PI3K/Akt/Nedd4-2 pathway in LPS-induced acute lung injury

2021 ◽  
Author(s):  
Yuanxu Jiang ◽  
Mingzhu Xia ◽  
Jing Xu ◽  
Qiang Huang ◽  
Zhongliang Dai ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Sodium Channel ◽  
Pulmonary Edema ◽  
Cell Injury ◽  
A549 Cells ◽  
Alveolar Epithelial ◽  
Phosphorylated Akt ◽  
Epithelial Sodium Channel Enac

AbstractDexmedetomidine (Dex), a highly selective α2-adrenergic receptor (α2AR) agonist, has an anti-inflammatory property and can alleviate pulmonary edema in lipopolysaccharide (LPS)-induced acute lung injury (ALI), but the mechanism is still unclear. In this study, we attempted to investigate the effect of Dex on alveolar epithelial sodium channel (ENaC) in the modulation of alveolar fluid clearance (AFC) and the underlying mechanism. Lipopolysaccharide (LPS) was used to induce acute lung injury (ALI) in rats and alveolar epithelial cell injury in A549 cells. In vivo, Dex markedly reduced pulmonary edema induced by LPS through promoting AFC, prevented LPS-induced downregulation of α-, β-, and γ-ENaC expression, attenuated inflammatory cell infiltration in lung tissue, reduced the concentrations of TNF-α, IL-1β, and IL-6, and increased concentrations of IL-10 in bronchoalveolar lavage fluid (BALF). In A549 cells stimulated with LPS, Dex attenuated LPS-mediated cell injury and the downregulation of α-, β-, and γ-ENaC expression. However, all of these effects were blocked by the PI3K inhibitor LY294002, suggesting that the protective role of Dex is PI3K-dependent. Additionally, Dex increased the expression of phosphorylated Akt and reduced the expression of Nedd4-2, while LY294002 reversed the effect of Dex in vivo and in vitro. Furthermore, insulin-like growth factor (IGF)-1, a PI3K agonists, promoted the expression of phosphorylated Akt and reduced the expression of Nedd4-2 in LPS-stimulated A549 cells, indicating that Dex worked through PI3K, and Akt and Nedd4-2 are downstream of PI3K. In conclusion, Dex alleviates pulmonary edema by suppressing inflammatory response in LPS-induced ALI, and the mechanism is partly related to the upregulation of ENaC expression via the PI3K/Akt/Nedd4-2 signaling pathway.

scholarly journals Claudin-4 augments alveolar epithelial barrier function and is induced in acute lung injury

2009 ◽  
Vol 297 (2) ◽  
pp. L219-L227 ◽  
Author(s):  
Charlie Wray ◽  
Ying Mao ◽  
Jue Pan ◽  
Anita Chandrasena ◽  
Frank Piasta ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Tight Junction ◽  
Pulmonary Edema ◽  
Barrier Function ◽  
Mapk Pathway ◽  
Paracellular Transport ◽  
Epithelial Barrier ◽  
Altered Expression ◽  
Alveolar Epithelial

Intact alveolar barrier function is associated with better outcomes in acute lung injury patients; however, the regulation of alveolar epithelial paracellular transport during lung injury has not been extensively investigated. This study was undertaken to determine whether changes in tight junction claudin expression affect alveolar epithelial barrier properties and to determine the mechanisms of altered expression. In anesthetized mice exposed to ventilator-induced lung injury, claudin-4 was specifically induced among tight junction structural proteins. Real-time PCR showed an eightfold increase in claudin-4 expression in the lung injury model. To examine the role of this protein in barrier regulation, claudin-4 function was inhibited with small interfering RNA (siRNA) and a blocking peptide derived from the binding domain of Clostridium perfringens enterotoxin (CPEBD). Inhibition of claudin-4 decreased transepithelial electrical resistance but did not alter macromolecule permeability in primary rat and human epithelial cells. In mice, CPEBD decreased air space fluid clearance >33% and resulted in pulmonary edema during moderate tidal volume ventilation that did not induce edema in control peptide-treated mice. In vitro phorbol ester induced a ninefold increase in claudin-4 expression that was dependent on PKC activation and the JNK MAPK pathway. These data establish that changes in alveolar epithelial claudin expression influence paracellular transport, alveolar fluid clearance rates, and susceptibility to pulmonary edema. We hypothesize that increased claudin-4 expression early in acute lung injury represents a mechanism to limit pulmonary edema and that the regulation of alveolar epithelial claudin expression may be a novel target for acute lung injury therapy.

scholarly journals New insights into the mechanisms of pulmonary edema in acute lung injury

2018 ◽  
Vol 6 (2) ◽  
pp. 32-32 ◽  
Author(s):  
Raquel Herrero ◽  
Gema Sanchez ◽  
Jose Angel Lorente
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Pulmonary Edema

scholarly journals Recipient T lymphocytes modulate the severity of antibody-mediated transfusion-related acute lung injury

Blood ◽  
2010 ◽  
Vol 116 (16) ◽  
pp. 3073-3079 ◽  
Author(s):  
Yoke Lin Fung ◽  
Michael Kim ◽  
Arata Tabuchi ◽  
Rukhsana Aslam ◽  
Edwin R. Speck ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
T Lymphocytes ◽  
Lung Injury ◽  
Pulmonary Edema ◽  
Critical Role ◽  
Severe Combined Immunodeficiency ◽  
Lung Damage ◽  
Moderate Hypothermia ◽  
Combined Immunodeficiency ◽  
Histocompatibility Complex

Abstract Transfusion-related acute lung injury (TRALI) is a serious complication of transfusion and has been ranked as one of the leading causes of transfusion-related fatalities. Nonetheless, many details of the immunopathogenesis of TRALI, particularly with respect to recipient factors are unknown. We used a murine model of antibody-mediated TRALI in an attempt to understand the role that recipient lymphocytes might play in TRALI reactions. Intravenous injection of an IgG2a antimurine major histocompatibility complex class I antibody (34-1-2s) into BALB/c mice induced moderate hypothermia and pulmonary granulocyte accumulation but no pulmonary edema nor mortality. In contrast, 34-1-2s injections into mice with severe combined immunodeficiency caused severe hypothermia, severe pulmonary edema, and approximately 40% mortality indicating a critical role for T and B lymphocytes in suppressing TRALI reactions. Adoptive transfer of purified CD8+ T lymphocytes or CD4+ T cells but not CD19+ B cells into the severe combined immunodeficiency mice alleviated the antibody-induced hypothermia, lung damage, and mortality, suggesting that T lymphocytes were responsible for the protective effect. Taken together, these results suggest that recipient T lymphocytes play a significant role in suppressing antibody-mediated TRALI reactions. They identify a potentially new recipient mechanism that controls the severity of TRALI reactions.

scholarly journals Derecruitment Test and Surfactant Therapy in Patients with Acute Lung Injury

2012 ◽  
Vol 2012 ◽  
pp. 1-6
Author(s):  
Alexey A. Smetkin ◽  
Vsevolod V. Kuzkov ◽  
Konstantin M. Gaidukov ◽  
Lars J. Bjertnaes ◽  
Mikhail Y. Kirov
Keyword(s):  
Acute Lung Injury ◽  
Gas Exchange ◽  
Lung Injury ◽  
Predictive Value ◽  
Conventional Therapy ◽  
Therapy Group ◽  
Lung Mechanics ◽  
Lung Water ◽  
Mechanically Ventilated ◽  
Water Index

Introduction. A recruitment maneuver (RM) may improve gas exchange in acute lung injury (ALI). The aim of our study was to assess the predictive value of a derecruitment test in relation to RM and to evaluate the efficacy of RM combined with surfactant instillation in patients with ALI.Materials and Methods. Thirteen adult mechanically ventilated patients with ALI were enrolled into a prospective pilot study. The patients received protective ventilation and underwent RM followed by a derecruitment test. After a repeat RM, bovine surfactant (surfactant group,n=6) or vehicle only (conventional therapy group,n=7) was instilled endobronchially. We registered respiratory and hemodynamic parameters, including extravascular lung water index (EVLWI).Results. The derecruitment test decreased the oxygenation in 62% of the patients. We found no significant correlation between the responses to the RM and to the derecruitment tests. The baseline EVLWI correlated with changes in SpO2following the derecruitment test. The surfactant did not affect gas exchange and lung mechanics but increased EVLWI at 24 and 32 hrs.Conclusions. Our study demonstrated no predictive value of the derecruitment test regarding the effects of RM. Surfactant instillation was not superior to conventional therapy and might even promote pulmonary edema in ALI.

Effect of eicosanoid inhibition on the development of pulmonary edema after acute lung injury

1996 ◽  
Vol 80 (3) ◽  
pp. 915-923 ◽  
Author(s):  
D. P. Schuster ◽  
A. H. Stephenson ◽  
S. Holmberg ◽  
P. Sandiford
Keyword(s):  
Acute Lung Injury ◽  
Oleic Acid ◽  
Lung Injury ◽  
Pulmonary Edema ◽  
Experimental Models ◽  
Nuclear Medicine Imaging ◽  
Lung Water ◽  
Edema Formation ◽  
Cyclooxygenase Inhibition ◽  
Positron Emission

In experimental models of acute lung injury, cyclooxygenase inhibition improves oxygenation, presumably by causing a redistribution of blood flow away from edematous lung regions. This effect on perfusion pattern could also reduce alveolar edema formation. On the other hand, pulmonary pressures usually increase after cyclooxygenase inhibition, an effect that could exacerbate edema accumulation. Therefore we tested the following hypothesis: the total accumulation of pulmonary edema in dogs during a 24- to 28-h period of observation after acute lung injury caused by oleic acid will be less in a group of animals treated with meclofenamate (n = 6) or with the thromboxane-receptor blocker ONO-3708 (n = 5) than in a group of animals treated with oleic acid alone (placebo, n = 6). Lung water concentrations (LWC), the regional pattern of pulmonary perfusion, and protein permeability were measured with the nuclear medicine imaging technique of positron emission tomography. After 24-28 h, LWC was significantly less (P < 0.05) in the ONO-3708 group than in the meclofenamate group (a similar trend was seen compared with the placebo group, P = 0.12). After 24-28 h, pulmonary arterial pressures were highest in the meclofenamate group. Regardless of group, the only significant correlation with the change in LWC was with the integral of pulmonary pressures over the 24- to 28-h period. The data suggest that thromboxane inhibition will reduce edema accumulation in acute lung injury but that this effect depends on reducing as much as possible the simultaneous development of pulmonary hypertension from other causes.

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