N-acetylcysteine attenuates ventilator-induced lung injury in an isolated and perfused rat lung model

Chi Huei Chiang, Chiao Hui Chuang, Shiou Ling Liu, Chih Feng Chian, Haibo Zhang, Jay H Ryu

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

N-acetylcysteine (NAC) suppresses the generation of reactive oxygen species (ROS) that are implicated in ventilator-induced lung injury (VILI). We thus hypothesised that NAC attenuates VILI. VILI was induced by mechanical ventilation with a tidal volume (Vt) of 15 ml kg -1 in isolated and perfused rat lung. NAC was administered in the perfusate prior to the onset of mechanical ventilation. A group ventilated with low Vt of 5 ml kg -1 served as control. Haemodynamics, lung injury indices, inflammatory responses and activation of apoptotic pathways were determined upon completion of the mechanical ventilation. There was an increase in lung permeability and lung weight gain after mechanical ventilation with high Vt, compared to low Vt. The levels of inflammatory cytokines including interleukin-1β (IL-1β), tumour necrosis factor-α (TNF-α) and macrophage inflammatory protein-2 (MIP-2) increased in lung lavage fluids; the concentrations of H 2O 2 were higher in lung lavage fluids, and the expression of myeloperoxidase (MPO), JNK, P38, pAKT and caspase-3 in lung tissue was greater in the high Vt than in the low Vt group. The concentrations of glutathione (GSH) in lung tissue were higher in low Vt than those in high Vt. The administration of NAC increased GSH, attenuated ROS, cytokines, MPO, JNK, pAKT and caspase-3 and lung permeability associated with decreased activation of nuclear factor-κB. VILI is associated with inflammatory responses including the generation of ROS, cytokines and the activation of mitogen-activated protein kinase cascade. The administration of NAC attenuates the inflammatory responses, apoptosis and VILI in the isolated, perfused rat lung model.

Original languageEnglish (US)
Pages (from-to)1257-1263
Number of pages7
JournalInjury
Volume43
Issue number8
DOIs
StatePublished - Aug 2012

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Ventilator-Induced Lung Injury
Acetylcysteine
Lung
Artificial Respiration
Reactive Oxygen Species
Bronchoalveolar Lavage Fluid
Cytokines
Caspase 3
Peroxidase
Permeability
Chemokine CXCL2
Tidal Volume
Lung Injury
Mitogen-Activated Protein Kinases
Interleukin-1
Weight Gain
Glutathione
Tumor Necrosis Factor-alpha
Hemodynamics

Keywords

  • ARDS
  • Inflammation
  • MAPK
  • N-acetylcysteine
  • NF-κB
  • ROS

ASJC Scopus subject areas

  • Emergency Medicine
  • Orthopedics and Sports Medicine

Cite this

N-acetylcysteine attenuates ventilator-induced lung injury in an isolated and perfused rat lung model. / Chiang, Chi Huei; Chuang, Chiao Hui; Liu, Shiou Ling; Chian, Chih Feng; Zhang, Haibo; Ryu, Jay H.

In: Injury, Vol. 43, No. 8, 08.2012, p. 1257-1263.

Research output: Contribution to journalArticle

Chiang, Chi Huei ; Chuang, Chiao Hui ; Liu, Shiou Ling ; Chian, Chih Feng ; Zhang, Haibo ; Ryu, Jay H. / N-acetylcysteine attenuates ventilator-induced lung injury in an isolated and perfused rat lung model. In: Injury. 2012 ; Vol. 43, No. 8. pp. 1257-1263.
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AU - Chuang, Chiao Hui

AU - Liu, Shiou Ling

AU - Chian, Chih Feng

AU - Zhang, Haibo

AU - Ryu, Jay H

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