scholarly journals LTB4 Promotes Acute Lung Injury via Upregulating the PLCε-1/TLR4/NF-κB Pathway in One-Lung Ventilation

2022 ◽  
Vol 2022 ◽  
pp. 1-15
Author(s):  
Jing Luo ◽  
Qingjie Ma ◽  
Heng Tang ◽  
Xi Zou ◽  
Xin Guo ◽  
...  

Background. Mechanical ventilation (MV) can provoke acute lung injury (ALI) by increasing inflammation activation and disrupting the barrier in lung tissues even causing death. However, the inflammation-related molecules and pathways in MV-induced ALI remain largely unknown. Hence, the purposes of this study are to examine the role and mechanism of a novel inflammation-related molecule, leukotriene B4 (LTB4), in ALI. Methods. The functions of LTB4 in one-lung ventilation (OLV) model were detected by the loss-of-function experiments. H&E staining was used to examine the pathologic changes of lung tissues. Functionally, PLCε-1 knockdown and Toll-like receptor 4 (TLR4)/NF-κB pathway inhibitor were used to detect the regulatory effects of LTB4 on the phospholipase Cε (PLCε-1)/TLR4/nuclear factor-kappa B (NF-κB) pathway. The levels of genes and proteins were determined by RT-qPCR and western blotting assay. The levels of inflammation cytokines and chemokines were measured by ELISA. Results. Here, we found LTA4H, leukotriene B (4) receptor 1 (BLT1), LTB4, and PLCε-1 upregulated in OLV rats and associated with inflammatory activation and lung permeability changes of lung tissues. Inhibition of LTB4 alleviated the OLV-induced ALI by inhibiting inflammatory activation and lung permeability changes of lung tissues. For mechanism analyses, LTB4 promoted OLV-induced ALI by activating the PLCε-1/TLR4/NF-κB pathway. Conclusion. LTB4 induced ALI in OLV rats by activating the PLCε-1/TLR4/NF-κB pathway. Our findings might supply a new potential therapeutic for OLV-induced ALI.

2018 ◽  
Vol 56 (1) ◽  
pp. 88-106 ◽  
Author(s):  
S. Patrick Bender ◽  
Erik P. Anderson ◽  
Robert I. Hieronimus ◽  
Ariel Bensimhon

2017 ◽  
Vol 103 (6) ◽  
pp. 495-503 ◽  
Author(s):  
Filippo Bernasconi ◽  
Federico Piccioni

One-lung ventilation (OLV) is an anesthesiological technique that is increasingly being used beyond thoracic surgery. This requires specific skills and knowledge about airway management, maintenance of gas exchange and prevention of acute lung injury. Sometimes maintaining adequate gas exchange and minimizing acute lung injury may be opposing processes. Parameters validated for OLV titration still have not been found, but a multimodal approach based on low tidal volume, end-expiratory pressure application and alveolar recruitment maneuvers is considered the best way to ensure protective ventilation and reduce lung damage. The purpose of this review is to analyze all these factors using the latest scientific evidence and the opinions of the most influential authors.


2014 ◽  
Vol 121 (2) ◽  
pp. 249-259 ◽  
Author(s):  
Cai Li ◽  
Miao Xu ◽  
Yan Wu ◽  
Yun-Sheng Li ◽  
Wen-Qi Huang ◽  
...  

Abstract Background: Remote ischemic preconditioning (RIPC) may confer the protection in critical organs. The authors hypothesized that limb RIPC would reduce lung injury in patients undergoing pulmonary resection. Methods: In a randomized, prospective, parallel, controlled trial, 216 patients undergoing elective thoracic pulmonary resection under one-lung ventilation with propofol–remifentanil anesthesia were randomized 1:1 to receive either limb RIPC or conventional lung resection (control). Three cycles of 5-min ischemia/5-min reperfusion induced by a blood pressure cuff served as RIPC stimulus. The primary outcome was Pao2/Fio2. Secondary outcomes included other pulmonary variables, the incidence of in-hospital complications, markers of oxidative stress, and inflammatory response. Results: Limb RIPC significantly increased Pao2/Fio2 compared with control at 30 and 60 min after one-lung ventilation, 30 min after re-expansion, and 6 h after operation (238 ± 52 vs. 192 ± 67, P = 0.03; 223 ± 66 vs. 184 ± 64, P = 0.01; 385 ± 61 vs. 320 ± 79, P = 0.003; 388 ± 52 vs. 317 ± 46, P = 0.001, respectively). In comparison with control, it also significantly reduced serum levels of interleukin-6 and tumor necrosis factor-α at 6, 12, 24, and 48 h after operation and malondialdehyde levels at 60 min after one-lung ventilation and 30 min after re-expansion (all P < 0.01). The incidence of acute lung injury and the length of postoperative hospital stay were markedly reduced by limb RIPC compared with control (all P < 0.05). Conclusion: Limb RIPC attenuates acute lung injury via improving intraoperative pulmonary oxygenation in patients without severe pulmonary disease after lung resection under propofol–remifentanil anesthesia.


2020 ◽  
Author(s):  
Feiping Xia ◽  
Zhonghua Lu ◽  
Yuying Tang ◽  
Haibo Qiu ◽  
Yi Yang ◽  
...  

Abstract Objective: It is unclear how tidal volume (Vt) impacts patients during one-lung ventilation (OLV). A meta-analysis was performed to assess the effect of Vt on physiology and clinical outcomes in OLV patients. Methods: PubMed, Cochrane library, and Web of Science were retrieved until February 2020. Randomized controlled trials comparing the application of low and high Vt ventilation in adults with OLV were included. Demographic variables, Vt, physiology, and clinical outcomes were retrieved. Summary odds ratios (ORs) with 95% confidence intervals (CIs) and mean difference with standard deviation were calculated using a random-effects model.Results: 12 studies involving a total of 876 participants met inclusion criteria. Significant difference in blood interleukin-6 (IL-6) was observed between low Vt ventilation and high Vt ventilation (MD -35.51 pg/ml, 95% CI [-66.47, -4.54 pg/ml], p = 0.02). Low Vt ventilation decreased driving pressure (ΔP) (MD -6.02 cmH2O, 95% CI [-8.32, -3.72 cmH2O], p < 0.0001), Peak pressure (Ppeak) (MD -2.88 cmH2O, 95% CI [-4.60, -1.16 cmH2O], p = 0.001), and improved PaO2/FiO2 (MD 32.27 mmHg, 95% CI [19.54, 45.01 mmHg], p <0.00001). Risk of atelectasis was the same between the two groups. Furthermore, the study suggested that low Vt ventilation was associated with decreases in the risk of acute lung injury (OR 0.05, 95% CI [0.28, 0.88], p = 0.02). Decreased hospital length of stay in the low Vt group occurred when Vt was set 4-5 ml/kg (MD -0.78 d, 95% CI [-1.45, -0.11 d], p = 0.02).Conclusions: In OLV patients, low Vt ventilation improved PaO2/FiO2, and it was also associated with decreased blood IL-6, ΔP, Ppeak, and risk of acute lung injury, when the low Vt was set 4-5 ml/kg hospital length of stay was decreased .


2012 ◽  
Vol 25 (2) ◽  
pp. 78-85 ◽  
Author(s):  
Zhijian You ◽  
Dan Feng ◽  
Hongxia Xu ◽  
Minghua Cheng ◽  
Zhiqing Li ◽  
...  

1995 ◽  
Vol 78 (3) ◽  
pp. 1121-1131 ◽  
Author(s):  
T. J. VanderMeer ◽  
M. J. Menconi ◽  
B. P. O'Sullivan ◽  
V. A. Larkin ◽  
H. Wang ◽  
...  

The role of leukotriene B4 (LTB4) in the pathogenesis of acute lung injury was examined in endotoxemic pigs. In a preliminary study, the activity and specificity of an LTB4-receptor antagonist, LY-306669, were evaluated. In vitro, LY-306669 completely blocked the functional upregulation of phagocyte opsonin receptors induced by LTB4 but had a much smaller effect on opsonin receptor upregulation induced by platelet-activating factor. In pigs treatment with LY-306669 prevented leukopenia induced by injection of authentic LTB4 but had no effect on the hematologic or hemodynamic effects of PAF or U-48816, a thromboxane-A2 mimetic. In a second study, pigs received an intravenous priming dose of lipopolysaccharide (LPS) at time (t) = -18 h and were randomized to receive 1) no further treatment (n = 5), 2) LPS (250 micrograms/kg over 1 h beginning at t = 0 h) and LY-306669 (10 mg/kg bolus and 3 mg.kg-1.h-1 infusion beginning at t = -15 min) (n = 7), or 3) LPS and vehicle (n = 6). Treatment with LY-306669 significantly ameliorated LPS-induced hypoxemia, pulmonary edema, and alveolitis. These data suggest that LTB4 is an important mediator of pulmonary dysfunction and transendothelial migration of neutrophils in LPS-induced acute lung injury.


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