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 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 inhaled
hydrogen therapy could ameliorate VILI due to its antioxidant and anti-inflammatory properties.
Methods: VILI was generated in male C57BL6 mice by performing a racheostomy and placing the mice on a mechanical ventilator (tidal volume of 30 ml/kg without positive endexpiratory 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.
Key

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Huang, C. S. Articles by Toyoda, Y. PubMed Articles by Huang, C. S. Articles by Toyoda, Y. Hydrogen Gas Inhalation Attenuates Ventilator-Induced Lung Injury In Mice Chien-Sheng Huang, Atsunori Nakao, Songsoo Lee, Zhiliang Wang, Norihisa Shigemura, Timothy R Billar, James Luketich, and Yoshiya Toyoda You have reached the most complete version of this article accessible without further authentication. More complete versions are available. Link to article

 

American Journal of Respiratory and Critical Care Medicine

这个研究我在日本开会期间听过作者的报告，确实十分有新意思，可惜现在没有能拿到全文，预先放这里，等全文后再进行深入介绍。根据回忆是，通过NFkB的信号通路实现作用，这个研究给我们现在的研究提出了重要的研究设计参考，我们过去的研究对分子机制的研究太肤浅，因此发表论文存在很大不足。这是非常值得我们学习的。

[3:20 PM] Hydrogen Gas Inhalation Attenuates Ventilator-Induced Lung Injury in Mice, [Publication Page: A3751]

网上地址：https://cms.psavcns.com/cAbstract/itinerary/title-72.html

C.-S. Huang, M.D., A. Nakao, M.D, S. Lee, M.D., Z. Wang, M.D, PhD, N. Shigemura, M.D, PhD, T.R. Billar, M.D, PhD, J. Luketich, M.D., Y. Toyoda, M.D, PhD
Pittsburgh, PA/US

 

 

Table 1 Arterial blood gas changes in VILI

	Sham (N=2)	VILI (air) (N=6)	VILI( 2%H2) (N=6)
pH	7.26±0.06	7.24±0.04	7.25±0.04
PaO2 (mmHg)	88.0±9.9	79.7±5.4	92.0±3.8*
PaCO2 (mmHg)	37.6±0.1	55.8±5.7	49.7±6.0
HCO3- (mmol/l)	16.9±2.3	23.1±0.8	21.7±3.7
BE(mmol/l)	-10±2.8	-4.3±0.8	-5.0±3.9
SaO2 (%)	95.0±2.8	92.8±1.7	95.2±1.3*

Table 2 Real-Time RT-PCR analysis for inflammatory mediators in VILI

	Sham (N=2)	VILI (air) (N=5)	VILI( 2%H2) (N=5)
TNF-α mRNA	12.9±1.7	135.2±67.7	54.7±27.9
IL-1β mRNA	15.1±9.9	180.6±66.9	46.1±28.4*
IL-6 mRNA	3.6±0.4	21.9±12.0	8.8±3.6*
CCL2 mRNA	23.8±7.8	112.5±56.7	36.3±21.2*
Egr-1 mRNA	88.6±15.5	162.2±33.6	106.6±13.9*

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