Hydrogen gas attenuates embryonic gene expression and prevents left ventricular remodeling induced by intermittent hypoxia in cardiomyopathic hamsters

Am J Physiol Heart Circ Physiol. 2014 Dec 1;307(11):H1626-33. doi: 10.1152/ajpheart.00228.2014. Epub 2014 Oct 3.


The prevalence of sleep apnea is very high in patients with heart failure (HF). The aims of this study were to investigate the influence of intermittent hypoxia (IH) on the failing heart and to evaluate the antioxidant effect of hydrogen gas. Normal male Syrian hamsters (n = 22) and cardiomyopathic (CM) hamsters (n = 33) were exposed to IH (repeated cycles of 1.5 min of 5% oxygen and 5 min of 21% oxygen for 8 h during the daytime) or normoxia for 14 days. Hydrogen gas (3.05 vol/100 vol) was inhaled by some CM hamsters during hypoxia. IH increased the ratio of early diastolic mitral inflow velocity to mitral annulus velocity (E/e', 21.8 vs. 16.9) but did not affect the LV ejection fraction (EF) in normal Syrian hamsters. However, IH increased E/e' (29.4 vs. 21.5) and significantly decreased the EF (37.2 vs. 47.2%) in CM hamsters. IH also increased the cardiomyocyte cross-sectional area (672 vs. 443 μm(2)) and interstitial fibrosis (29.9 vs. 9.6%), along with elevation of oxidative stress and superoxide production in the left ventricular (LV) myocardium. Furthermore, IH significantly increased the expression of brain natriuretic peptide, β-myosin heavy chain, c-fos, and c-jun mRNA in CM hamsters. Hydrogen gas inhalation significantly decreased both oxidative stress and embryonic gene expression, thus preserving cardiac function in CM hamsters. In conclusion, IH accelerated LV remodeling in CM hamsters, at least partly by increasing oxidative stress in the failing heart. These findings might explain the poor prognosis of patients with HF and sleep apnea.

Keywords: cardiomyopathic hamster; heart failure; hydrogen gas; intermittent hypoxia; oxidative stress.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aldehydes / pharmacology
  • Animals
  • Body Weight / drug effects
  • Cardiomyopathies / diagnostic imaging
  • Cardiomyopathies / genetics
  • Cardiomyopathies / pathology*
  • Cricetinae
  • Cysteine Proteinase Inhibitors / pharmacology
  • Gases
  • Gene Expression Regulation, Developmental / drug effects*
  • Heart Ventricles / drug effects
  • Hydrogen / pharmacology*
  • Hypoxia / pathology*
  • Mesocricetus
  • Organ Size / drug effects
  • Superoxides / metabolism
  • Ultrasonography
  • Ventricular Remodeling / drug effects*


  • Aldehydes
  • Cysteine Proteinase Inhibitors
  • Gases
  • Superoxides
  • Hydrogen
  • 4-hydroxy-2-nonenal