Huang, CS and Kawamura, T and Lee, S and Tochigi, N and Shigemura, N and Buchholz, BM and Kloke, JD and Billiar, TR and Toyoda, Y and Nakao, A
(2010)
Hydrogen inhalation ameliorates ventilator-induced lung injury.
Critical Care, 14 (6).
ISSN 1364-8535
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. © 2010 Huang et al.; licensee BioMed Central Ltd.
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| Item Type: |
Article
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| Status: |
Published |
| Creators/Authors: |
| Creators | Email | Pitt Username | ORCID  |
|---|
| Huang, CS | | | | | Kawamura, T | | | | | Lee, S | | | | | Tochigi, N | | | | | Shigemura, N | nos9@pitt.edu | NOS9 | | | Buchholz, BM | bmb60@pitt.edu | BMB60 | | | Kloke, JD | | | | | Billiar, TR | | | | | Toyoda, Y | | | | | Nakao, A | | | |
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| Centers: |
Other Centers, Institutes, Offices, or Units > Center for Research on Health Care
Other Centers, Institutes, Offices, or Units > Thomas E. Starzl Transplantation Institute |
| Date: |
25 December 2010 |
| Date Type: |
Publication |
| Journal or Publication Title: |
Critical Care |
| Volume: |
14 |
| Number: |
6 |
| DOI or Unique Handle: |
10.1186/cc9389 |
| Schools and Programs: |
School of Medicine > Cardiothoracic Surgery
School of Medicine > Medicine
School of Medicine > Pathology
School of Medicine > Surgery |
| Refereed: |
Yes |
| ISSN: |
1364-8535 |
| Date Deposited: |
16 Nov 2016 18:32 |
| Last Modified: |
22 Jun 2021 13:55 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/30199 |
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