ArticleAmerican journal of respiratory and critical care medicine2005
5-Lipoxygenase deficiency prevents respiratory failure during ventilator-induced lung injury.
Article in American journal of respiratory and critical care medicine, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.
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Who cites it
24 citing papers in PubMed, 1 synthesis or guideline pooled it, 55 citations in OpenAlex.
- The role of fatty acid metabolism in acute lung injury: a special focus on immunometabolism.Cellular and molecular life sciences : CMLS · 2024Pooled it
- Trial
- Plasma Lipidomics Identify Pathways Linked to Acute Lung Injury in a Porcine One-Lung Ventilation Surgery Model.International journal of molecular sciences · 2026Article
- Zebrafish macrophages convert physical wound signals into rapid vascular permeabilization.Nature communications · 2026Article
- Metabolic Regulation in Acute Respiratory Distress Syndrome: Implications for Inflammation and Oxidative Stress.International journal of chronic obstructive pulmonary disease · 2025Review
- Impairment of hypoxic pulmonary vasoconstriction in acute respiratory distress syndrome.European respiratory review : an official journal of the European Respiratory Society · 2021Review
- The Leukotriene Receptor Antagonist Montelukast as a Potential COVID-19 Therapeutic.Frontiers in molecular biosciences · 2020Review
- Relation between Respiratory Mechanics, Inflammation, and Survival in Experimental Mechanical Ventilation.American journal of respiratory cell and molecular biology · 2019Article
- Abnormal liver phosphatidylcholine synthesis revealed in patients with acute respiratory distress syndrome.Journal of lipid research · 2018Article
- Endothelial nanomedicine for the treatment of pulmonary disease.Expert opinion on drug delivery · 2015Review
- Article
- Deletion of the murine cytochrome P450 Cyp2j locus by fused BAC-mediated recombination identifies a role for Cyp2j in the pulmonary vascular response to hypoxia.PLoS genetics · 2013Article
- Functional genomic assessment of phosgene-induced acute lung injury in mice.American journal of respiratory cell and molecular biology · 2013Article
- Regional lung derecruitment and inflammation during 16 hours of mechanical ventilation in supine healthy sheep.Anesthesiology · 2013Article
- Eliminating or blocking 12/15-lipoxygenase reduces neutrophil recruitment in mouse models of acute lung injury.Critical care (London, England) · 2012Article
- Genetically manipulated mouse models of lung disease: potential and pitfalls.American journal of physiology. Lung cellular and molecular physiology · 2012Review
- Time to generate ventilator-induced lung injury among mammals with healthy lungs: a unifying hypothesis.Intensive care medicine · 2011Article
- Effects of surfactant depletion on regional pulmonary metabolic activity during mechanical ventilation.Journal of applied physiology (Bethesda, Md. : 1985) · 2011Article
- Changes in cysteinyl leukotrienes during and after cardiac surgery with cardiopulmonary bypass in patients with and without chronic obstructive pulmonary disease.The Journal of thoracic and cardiovascular surgery · 2011Article
- Lung regional metabolic activity and gas volume changes induced by tidal ventilation in patients with acute lung injury.American journal of respiratory and critical care medicine · 2011Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
rationaleMechanical ventilation with high VT (HVT) progressively leads to lung injury and decreased efficiency of gas exchange. Hypoxic pulmonary vasoconstriction (HPV) directs blood flow to well-ventilated lung regions, preserving systemic oxygenation during pulmonary injury. Recent experimental studies have revealed an important role for leukotriene (LT) biosynthesis by 5-lipoxygenase (5LO) in the impairment of HPV by endotoxin.
objectivesTo investigate whether or not impairment of HPV contributes to the hypoxemia associated with HVT and to evaluate the role of LTs in ventilator-induced lung injury.
methodsWe studied wild-type and 5LO-deficient mice ventilated for up to 10 hours with low VT (LVT) or HVT.
resultsIn wild-type mice, HVT, but not LVT, increased pulmonary vascular permeability and edema formation, impaired systemic oxygenation, and reduced survival. HPV, as reflected by the increase in left pulmonary vascular resistance induced by left mainstem bronchus occlusion, was markedly impaired in animals ventilated with HVT. HVT ventilation increased bronchoalveolar lavage levels of LTs and neutrophils. In 5LO-deficient mice, the HVT-induced increase of pulmonary vascular permeability and worsening of respiratory mechanics were markedly attenuated, systemic oxygenation was preserved, and survival increased. Moreover, in 5LO-deficient mice, HVT ventilation did not impair the ability of left mainstem bronchus occlusion to increase left pulmonary vascular resistance. Administration of MK886, a 5LO-activity inhibitor, or MK571, a selective cysteinyl-LT(1) receptor antagonist, largely prevented ventilator-induced lung injury.
conclusionsThese results indicate that LTs play a central role in the lung injury and impaired oxygenation induced by HVT ventilation.
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