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Tojo K, Nagamine Y, Yazawa T, et al. Atelectasis causes alveolar hypoxia-induced inflammation during uneven mechanical ventilation in rats. Intensive Care Med Exp. 2015;3(1):56doi: 10.1186/s40635-015-0056-z.
Tojo, K., Nagamine, Y., Yazawa, T., Mihara, T., Baba, Y., Ota, S., Goto, T., & Kurahashi, K. (2015). Atelectasis causes alveolar hypoxia-induced inflammation during uneven mechanical ventilation in rats. Intensive care medicine experimental, 3(1), 56. https://doi.org/10.1186/s40635-015-0056-z
Tojo, Kentaro, et al. "Atelectasis causes alveolar hypoxia-induced inflammation during uneven mechanical ventilation in rats." Intensive care medicine experimental vol. 3,1 (2015): 56. doi: https://doi.org/10.1186/s40635-015-0056-z
Tojo K, Nagamine Y, Yazawa T, Mihara T, Baba Y, Ota S, Goto T, Kurahashi K. Atelectasis causes alveolar hypoxia-induced inflammation during uneven mechanical ventilation in rats. Intensive Care Med Exp. 2015 Dec;3(1):56. doi: 10.1186/s40635-015-0056-z. Epub 2015 Jun 19. PMID: 26215820; PMCID: PMC4480346.
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Intensive Care Med Exp. 2015 Dec;3(1):56. doi: 10.1186/s40635-015-0056-z. Epub 2015 Jun 19.

Atelectasis causes alveolar hypoxia-induced inflammation during uneven mechanical ventilation in rats.

Intensive care medicine experimental

Kentaro Tojo, Yusuke Nagamine, Takuya Yazawa, Takahiro Mihara, Yasuko Baba, Shuhei Ota, Takahisa Goto, Kiyoyasu Kurahashi

Affiliations

  1. Department of Anesthesiology and Critical Care Medicine, Yokohama City University Graduate School of Medicine, 3-9, Fukuura, Kanazawa-ku, Yokohama-city, Kanagawa, 236-0004, Japan, [email protected].

PMID: 26215820 PMCID: PMC4480346 DOI: 10.1186/s40635-015-0056-z

Abstract

BACKGROUND: Patients with acute respiratory distress syndrome receiving mechanical ventilation show inhomogeneous lung aeration. Atelectasis during uneven mechanical ventilation leads to alveolar hypoxia and could therefore result in lung inflammation and injury. We aimed to elucidate whether and how atelectasis causes alveolar hypoxia-induced inflammation during uneven mechanical ventilation in an open-chest differential-ventilation rat model.

METHODS: We first investigated inflammatory and histological changes in the bilateral lungs of unilaterally ventilated rats, in which the right lung was atelectatic and the left lung was ventilated with high tidal volume (HTV). In the next series, we investigated the effects of normal tidal volume (NTV) ventilation of the right lungs with 60 % O2 or 100 % N2 during HTV ventilation of the left lungs. Then, proinflammatory cytokine secretions were quantified from murine lung epithelial (MLE15) and murine alveolar macrophage (MH-S) cells cultured under a hypoxic condition (5 % O2) mimicking atelectasis. Further, activities of nuclear factor (NF)-κB and hypoxia-inducible factor (HIF)-1 were assessed in the nonventilated atelectatic lung and MLE15 cells cultured under the hypoxic condition. Finally, effects of NF-κB inhibition and HIF-1α knockdown on the cytokine secretions from MLE15 cells cultured under the hypoxic condition were assessed.

RESULTS: The nonventilated atelectatic lungs showed inflammatory responses and minimal histological changes comparable to those of the HTV-ventilated lungs. NTV ventilation with 60 % O2 attenuated the increase in chemokine (C-X-C motif) ligand (CXCL)-1 secretion and neutrophil accumulation observed in the atelectatic lungs, but that with 100 % N2 did not. MLE15 cells cultured with tumor necrosis factor (TNF)-α under the hypoxic condition showed increased CXCL-1 secretion. NF-κB and HIF-1α were activated in the nonventilated atelectatic lungs and MLE15 cells cultured under the hypoxic condition. NF-κB inhibition abolished the hypoxia-induced increase in CXCL-1 secretion from MLE15 cells, while HIF-1α knockdown augmented it.

CONCLUSIONS: Atelectasis causes alveolar hypoxia-induced inflammatory responses including NF-κB-dependent CXCL-1 secretion from lung epithelial cells. HIF-1 activation in lung epithelial cells is an anti-inflammatory response to alveolar hypoxia in atelectatic lungs.

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