Hydrogen inhalation ameliorates ventilator-induced lung injury

Chien Sheng Huang, Tomohiro Kawamura, Sungsoo Lee, Naobumi Tochigi, Norihisa Shigemura, Bettina M. Buchholz, John D. Kloke, Timothy R. Billiar, Yoshiya Toyoda, Atsunori Nakao

Research output: Contribution to journalArticle

55 Citations (Scopus)

Abstract

Introduction: Mechanical ventilation (MV) can provoke oxidative stress and an inflammatory response, and subsequently cause ventilator-induced lung injury (VILI), a major cause of mortality and morbidity of patients in the intensive care unit. Inhaled hydrogen can act as an antioxidant and may be useful as a novel therapeutic gas. We hypothesized that, owing to its antioxidant and anti-inflammatory properties, inhaled hydrogen therapy could ameliorate VILI.Methods: VILI was generated in male C57BL6 mice by performing a tracheostomy and placing the mice on a mechanical ventilator (tidal volume of 30 ml/kg without positive end-expiratory pressure, FiO2 0.21). The mice were randomly assigned to treatment groups and subjected to VILI with delivery of either 2% nitrogen or 2% hydrogen in air. Sham animals were given same gas treatments for two hours (n = 8 for each group). The effects of VILI induced by less invasive and longer exposure to MV (tidal volume of 10 ml/kg, 5 hours, FiO2 0.21) were also investigated (n = 6 for each group). Lung injury score, wet/dry ratio, arterial oxygen tension, oxidative injury, and expression of pro-inflammatory mediators and apoptotic genes were assessed at the endpoint of two hours using the high-tidal volume protocol. Gas exchange and apoptosis were assessed at the endpoint of five hours using the low-tidal volume protocol.Results: Ventilation (30 ml/kg) with 2% nitrogen in air for 2 hours resulted in deterioration of lung function, increased lung edema, and infiltration of inflammatory cells. In contrast, ventilation with 2% hydrogen in air significantly ameliorated these acute lung injuries. Hydrogen treatment significantly inhibited upregulation of the mRNAs for pro-inflammatory mediators and induced antiapoptotic genes. In the lungs treated with hydrogen, there was less malondialdehyde compared with lungs treated with nitrogen. Similarly, longer exposure to mechanical ventilation within lower tidal volume (10 mg/kg, five hours) caused lung injury including bronchial epithelial apoptosis. Hydrogen improved gas exchange and reduced VILI-induced apoptosis.Conclusions: Inhaled hydrogen gas effectively reduced VILI-associated inflammatory responses, at both a local and systemic level, via its antioxidant, anti-inflammatory and antiapoptotic effects.

Original languageEnglish
Article numberR234
JournalCritical Care
Volume14
Issue number6
DOIs
Publication statusPublished - Dec 25 2010
Externally publishedYes

Fingerprint

Ventilator-Induced Lung Injury
Inhalation
Hydrogen
Tidal Volume
Gases
Artificial Respiration
Lung
Nitrogen
Antioxidants
Air
Lung Injury
Apoptosis
Ventilation
Anti-Inflammatory Agents
Therapeutics
Positive-Pressure Respiration
Acute Lung Injury
Tracheostomy
Mechanical Ventilators
Malondialdehyde

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine
  • Medicine(all)

Cite this

Huang, C. S., Kawamura, T., Lee, S., Tochigi, N., Shigemura, N., Buchholz, B. M., ... Nakao, A. (2010). Hydrogen inhalation ameliorates ventilator-induced lung injury. Critical Care, 14(6), [R234]. https://doi.org/10.1186/cc9389

Hydrogen inhalation ameliorates ventilator-induced lung injury. / Huang, Chien Sheng; Kawamura, Tomohiro; Lee, Sungsoo; Tochigi, Naobumi; Shigemura, Norihisa; Buchholz, Bettina M.; Kloke, John D.; Billiar, Timothy R.; Toyoda, Yoshiya; Nakao, Atsunori.

In: Critical Care, Vol. 14, No. 6, R234, 25.12.2010.

Research output: Contribution to journalArticle

Huang, CS, Kawamura, T, Lee, S, Tochigi, N, Shigemura, N, Buchholz, BM, Kloke, JD, Billiar, TR, Toyoda, Y & Nakao, A 2010, 'Hydrogen inhalation ameliorates ventilator-induced lung injury', Critical Care, vol. 14, no. 6, R234. https://doi.org/10.1186/cc9389
Huang CS, Kawamura T, Lee S, Tochigi N, Shigemura N, Buchholz BM et al. Hydrogen inhalation ameliorates ventilator-induced lung injury. Critical Care. 2010 Dec 25;14(6). R234. https://doi.org/10.1186/cc9389
Huang, Chien Sheng ; Kawamura, Tomohiro ; Lee, Sungsoo ; Tochigi, Naobumi ; Shigemura, Norihisa ; Buchholz, Bettina M. ; Kloke, John D. ; Billiar, Timothy R. ; Toyoda, Yoshiya ; Nakao, Atsunori. / Hydrogen inhalation ameliorates ventilator-induced lung injury. In: Critical Care. 2010 ; Vol. 14, No. 6.
@article{3ed068fd238d41539a02ec4bb99f4ac6,
title = "Hydrogen inhalation ameliorates ventilator-induced lung injury",
abstract = "Introduction: Mechanical ventilation (MV) can provoke oxidative stress and an inflammatory response, and subsequently cause ventilator-induced lung injury (VILI), a major cause of mortality and morbidity of patients in the intensive care unit. Inhaled hydrogen can act as an antioxidant and may be useful as a novel therapeutic gas. We hypothesized that, owing to its antioxidant and anti-inflammatory properties, inhaled hydrogen therapy could ameliorate VILI.Methods: VILI was generated in male C57BL6 mice by performing a tracheostomy and placing the mice on a mechanical ventilator (tidal volume of 30 ml/kg without positive end-expiratory pressure, FiO2 0.21). The mice were randomly assigned to treatment groups and subjected to VILI with delivery of either 2{\%} nitrogen or 2{\%} hydrogen in air. Sham animals were given same gas treatments for two hours (n = 8 for each group). The effects of VILI induced by less invasive and longer exposure to MV (tidal volume of 10 ml/kg, 5 hours, FiO2 0.21) were also investigated (n = 6 for each group). Lung injury score, wet/dry ratio, arterial oxygen tension, oxidative injury, and expression of pro-inflammatory mediators and apoptotic genes were assessed at the endpoint of two hours using the high-tidal volume protocol. Gas exchange and apoptosis were assessed at the endpoint of five hours using the low-tidal volume protocol.Results: Ventilation (30 ml/kg) with 2{\%} nitrogen in air for 2 hours resulted in deterioration of lung function, increased lung edema, and infiltration of inflammatory cells. In contrast, ventilation with 2{\%} hydrogen in air significantly ameliorated these acute lung injuries. Hydrogen treatment significantly inhibited upregulation of the mRNAs for pro-inflammatory mediators and induced antiapoptotic genes. In the lungs treated with hydrogen, there was less malondialdehyde compared with lungs treated with nitrogen. Similarly, longer exposure to mechanical ventilation within lower tidal volume (10 mg/kg, five hours) caused lung injury including bronchial epithelial apoptosis. Hydrogen improved gas exchange and reduced VILI-induced apoptosis.Conclusions: Inhaled hydrogen gas effectively reduced VILI-associated inflammatory responses, at both a local and systemic level, via its antioxidant, anti-inflammatory and antiapoptotic effects.",
author = "Huang, {Chien Sheng} and Tomohiro Kawamura and Sungsoo Lee and Naobumi Tochigi and Norihisa Shigemura and Buchholz, {Bettina M.} and Kloke, {John D.} and Billiar, {Timothy R.} and Yoshiya Toyoda and Atsunori Nakao",
year = "2010",
month = "12",
day = "25",
doi = "10.1186/cc9389",
language = "English",
volume = "14",
journal = "Critical Care",
issn = "1466-609X",
publisher = "Springer Science + Business Media",
number = "6",

}

TY - JOUR

T1 - Hydrogen inhalation ameliorates ventilator-induced lung injury

AU - Huang, Chien Sheng

AU - Kawamura, Tomohiro

AU - Lee, Sungsoo

AU - Tochigi, Naobumi

AU - Shigemura, Norihisa

AU - Buchholz, Bettina M.

AU - Kloke, John D.

AU - Billiar, Timothy R.

AU - Toyoda, Yoshiya

AU - Nakao, Atsunori

PY - 2010/12/25

Y1 - 2010/12/25

N2 - Introduction: Mechanical ventilation (MV) can provoke oxidative stress and an inflammatory response, and subsequently cause ventilator-induced lung injury (VILI), a major cause of mortality and morbidity of patients in the intensive care unit. Inhaled hydrogen can act as an antioxidant and may be useful as a novel therapeutic gas. We hypothesized that, owing to its antioxidant and anti-inflammatory properties, inhaled hydrogen therapy could ameliorate VILI.Methods: VILI was generated in male C57BL6 mice by performing a tracheostomy and placing the mice on a mechanical ventilator (tidal volume of 30 ml/kg without positive end-expiratory pressure, FiO2 0.21). The mice were randomly assigned to treatment groups and subjected to VILI with delivery of either 2% nitrogen or 2% hydrogen in air. Sham animals were given same gas treatments for two hours (n = 8 for each group). The effects of VILI induced by less invasive and longer exposure to MV (tidal volume of 10 ml/kg, 5 hours, FiO2 0.21) were also investigated (n = 6 for each group). Lung injury score, wet/dry ratio, arterial oxygen tension, oxidative injury, and expression of pro-inflammatory mediators and apoptotic genes were assessed at the endpoint of two hours using the high-tidal volume protocol. Gas exchange and apoptosis were assessed at the endpoint of five hours using the low-tidal volume protocol.Results: Ventilation (30 ml/kg) with 2% nitrogen in air for 2 hours resulted in deterioration of lung function, increased lung edema, and infiltration of inflammatory cells. In contrast, ventilation with 2% hydrogen in air significantly ameliorated these acute lung injuries. Hydrogen treatment significantly inhibited upregulation of the mRNAs for pro-inflammatory mediators and induced antiapoptotic genes. In the lungs treated with hydrogen, there was less malondialdehyde compared with lungs treated with nitrogen. Similarly, longer exposure to mechanical ventilation within lower tidal volume (10 mg/kg, five hours) caused lung injury including bronchial epithelial apoptosis. Hydrogen improved gas exchange and reduced VILI-induced apoptosis.Conclusions: Inhaled hydrogen gas effectively reduced VILI-associated inflammatory responses, at both a local and systemic level, via its antioxidant, anti-inflammatory and antiapoptotic effects.

AB - Introduction: Mechanical ventilation (MV) can provoke oxidative stress and an inflammatory response, and subsequently cause ventilator-induced lung injury (VILI), a major cause of mortality and morbidity of patients in the intensive care unit. Inhaled hydrogen can act as an antioxidant and may be useful as a novel therapeutic gas. We hypothesized that, owing to its antioxidant and anti-inflammatory properties, inhaled hydrogen therapy could ameliorate VILI.Methods: VILI was generated in male C57BL6 mice by performing a tracheostomy and placing the mice on a mechanical ventilator (tidal volume of 30 ml/kg without positive end-expiratory pressure, FiO2 0.21). The mice were randomly assigned to treatment groups and subjected to VILI with delivery of either 2% nitrogen or 2% hydrogen in air. Sham animals were given same gas treatments for two hours (n = 8 for each group). The effects of VILI induced by less invasive and longer exposure to MV (tidal volume of 10 ml/kg, 5 hours, FiO2 0.21) were also investigated (n = 6 for each group). Lung injury score, wet/dry ratio, arterial oxygen tension, oxidative injury, and expression of pro-inflammatory mediators and apoptotic genes were assessed at the endpoint of two hours using the high-tidal volume protocol. Gas exchange and apoptosis were assessed at the endpoint of five hours using the low-tidal volume protocol.Results: Ventilation (30 ml/kg) with 2% nitrogen in air for 2 hours resulted in deterioration of lung function, increased lung edema, and infiltration of inflammatory cells. In contrast, ventilation with 2% hydrogen in air significantly ameliorated these acute lung injuries. Hydrogen treatment significantly inhibited upregulation of the mRNAs for pro-inflammatory mediators and induced antiapoptotic genes. In the lungs treated with hydrogen, there was less malondialdehyde compared with lungs treated with nitrogen. Similarly, longer exposure to mechanical ventilation within lower tidal volume (10 mg/kg, five hours) caused lung injury including bronchial epithelial apoptosis. Hydrogen improved gas exchange and reduced VILI-induced apoptosis.Conclusions: Inhaled hydrogen gas effectively reduced VILI-associated inflammatory responses, at both a local and systemic level, via its antioxidant, anti-inflammatory and antiapoptotic effects.

UR - http://www.scopus.com/inward/record.url?scp=78650447961&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=78650447961&partnerID=8YFLogxK

U2 - 10.1186/cc9389

DO - 10.1186/cc9389

M3 - Article

VL - 14

JO - Critical Care

JF - Critical Care

SN - 1466-609X

IS - 6

M1 - R234

ER -