| Cyclooxygenase inhibition in ventilator-induced lung injury. | |
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MedLine Citation:
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PMID: 21048090 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: We tested the hypothesis that inhibition of cyclooxygenase (COX) attenuates in vivo ventilator-induced lung injury (VILI) in a prospective, randomized laboratory investigation in a university-affiliated laboratory. Adult male rats were anesthetized and randomized with or without nonselective COX inhibition (ibuprofen) and were subjected to injurious mechanical ventilation (positive end-expiratory pressure = 0; peak inspiratory pressure = 21 mm Hg). METHODS: We investigated the profile of VILI (respiratory mechanics, cytokines, eicosanoids), expression of COX enzymes, and activation of nuclear factor (NF)-κB in ibuprofen- versus vehicle-treated animals. Injurious ventilation caused lung injury (i.e., decrement in compliance, tissue edema, and elevated inflammatory cytokines, eicosanoids, and COX-2). RESULTS: Pretreatment with ibuprofen that effectively inhibited eicosanoid synthesis and COX-2 activity increased survival and attenuated lung edema and decrement in respiratory mechanics. Ibuprofen had no modulatory effect on ventilator-induced activation of NF-κB or inflammatory cytokines (tumor necrosis factor-α, interleukin [IL]-1β, IL-6, GRO/KC [growth-related oncogene/keratinocyte chemoattractant]). COX activity seems important in the pathogenesis of VILI in the in vivo rat. Inhibition of COX provides significant protection (i.e., survival, pulmonary function) in VILI, but without affecting levels of important mediators (tumor necrosis factor-α, IL-1β, IL-6, GRO/KC) or activation of NF-κB. CONCLUSIONS: These data confirm that nonselective COX inhibition provides partial protection against VILI and that the NF-κB signaling pathway is not exclusively eicosanoid dependent. Studies of COX inhibition in ventilator-associated lung injury might benefit from multimodal targeting that includes a comprehensive focus on inflammatory cytokines and NF-κB. |
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Authors:
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Takehiro Niitsu; Shinya Tsuchida; Vanya Peltekova; Doreen Engelberts; Ian Copland; Gail Otulakowski; Martin Post; Brian P Kavanagh |
Publication Detail:
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Type: Comparative Study; Journal Article; Research Support, Non-U.S. Gov't Date: 2010-11-03 |
Journal Detail:
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Title: Anesthesia and analgesia Volume: 112 ISSN: 1526-7598 ISO Abbreviation: Anesth. Analg. Publication Date: 2011 Jan |
Date Detail:
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Created Date: 2010-12-21 Completed Date: 2011-01-20 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 1310650 Medline TA: Anesth Analg Country: United States |
Other Details:
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Languages: eng Pagination: 143-9 Citation Subset: AIM; IM |
Affiliation:
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Program in Physiology & Experimental Medicine, Hospital for Sick Children, Toronto, Canada. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Blood Gas Analysis / methods Cyclooxygenase Inhibitors / therapeutic use* Male Prospective Studies Random Allocation Rats Rats, Sprague-Dawley Ventilator-Induced Lung Injury / drug therapy*, enzymology* |
| Grant Support | |
ID/Acronym/Agency:
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MOP-15272//Canadian Institutes of Health Research |
| Chemical | |
Reg. No./Substance:
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0/Cyclooxygenase Inhibitors |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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