Parecoxib reduced ventilation induced lung injury in acute respiratory distress syndrome

Fan-You Meng,Ying-Nan Ju,Wei Gao

doi:10.1186/s40360-017-0131-z

Abstract

BackgroundCyclooxygenase-2 (COX-2) contributes to ventilation induced lung injury (VILI) and acute respiratory distress syndrome (ARDS). The objective of present study was to observe the therapeutic effect of parecoxib on VILI in ARDS.MethodsIn this parallel controlled study performed at Harbin Medical University, China between January 2016 and March 2016, 24 rats were randomly allocated into sham group (S), volume ventilation group/ARDS (VA), parecoxib/volume ventilation group/ARDS (PVA). Rats in the S group only received anesthesia; rats in the VA and PVA group received intravenous injection of endotoxin to induce ARDS, and then received ventilation. Rats in the VA and PVA groups were treated with intravenous injection of saline or parecoxib. The ratio of arterial oxygen pressure to fractional inspired oxygen (PaO2/FiO2), the wet to dry weight ratio of lung tissue, inflammatory factors in serum and bronchoalveolar lavage fluid (BALF), and histopathologic analyses of lung tissue were examined. In addition, survival was calculated at 24 h after VILI.ResultsCompared to the VA group, in the PVA group, PaO2/FiO2 was significantly increased; lung tissue wet to dry weight ratio; macrophage and neutrophil counts, total protein and neutrophil elastase levels in BALF; tumor necrosis factor-α, interleukin-1β, and prostaglandin E2 levels in BALF and serum; and myeloperoxidase (MPO) activity, malondialdehyde levels, and Bax and COX-2 protein levels in lung tissue were significantly decreased, while Bcl-2 protein levels were significantly increased. Lung histopathogical changes and apoptosis were reduced by parecpxib in the PVA group. Survival was increased in the PVA group.ConclusionsParecoxib improves gas exchange and epithelial permeability, decreases edema, reduces local and systemic inflammation, ameliorates lung injury and apoptosis, and increases survival in a rat model of VILI.

Highlights

Cyclooxygenase-2 (COX-2) contributes to ventilation induced lung injury (VILI) and acute respiratory distress syndrome (ARDS)
Parecoxib improved gas exchange and pulmonary capillary permeability in VILI Compared to the S group, the PaO2/FiO2 ratio was decreased after 4 h of Mechanical ventilation (MV) in the ventilation group/ARDS (VA) and parecoxib/ volume ventilation group/ARDS (PVA) groups (Fig. 1a), and the ratio of Wet/dry weight (W/D) weight and protein concentration in bronchoalveolar lavage fluid (BALF) were dramatically increased (Fig. 1b and c)
Parecoxib improved survival following VILI Compared to the VA group, survival time in the PVA group was significantly prolonged (P < 0.001) (Fig. 8)

Summary

Introduction

Cyclooxygenase-2 (COX-2) contributes to ventilation induced lung injury (VILI) and acute respiratory distress syndrome (ARDS). MV with large tidal volume can result in regional overdistention of alveoli and airways, and the release of proinflammatory cytokines and prostanoids. This can cause local inflammation and lung injury [2], as well. Patients with acute respiratory distress syndrome (ARDS) or prior lung injury usually require MV support to guarantee oxygenation [3], and are susceptible to VILI. Lung protective strategies and other therapies are used during MV in ARDS patients, the therapeutic effect remains unsatisfactory [4,5,6].

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