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Cyclooxygenase inhibition in ventilator-induced lung injury.

Abstract：

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.

journal_name

Anesth Analg

journal_title

Anesthesia and analgesia

authors

Niitsu T,Tsuchida S,Peltekova V,Engelberts D,Copland I,Otulakowski G,Post M,Kavanagh BP

doi

10.1213/ANE.0b013e3181fe4841

subject

Has Abstract

pub_date

2011-01-01 00:00:00

pages

143-9

issue

eissn

0003-2999

issn

1526-7598

pii

ANE.0b013e3181fe4841

journal_volume

112

pub_type

杂志文章

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Cyclooxygenase inhibition in ventilator-induced lung injury.