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

Abstract:

The prevalence of sleep apnea is much higher in patients with heart failure, and intermittent hypoxia (IH) relevant to sleep apnea might induce left ventricular (LV) remodeling. The aim of this study was to investigate the effect of repetitive hypoxic stress on failing heart and to evaluate the antioxidant effect of hydrogen gas. Male Syrian normal (n=22) and cardiomyopathic (CM) (n=33) hamsters were exposed to IH (5-min cycles of 5% and 21% oxygen for 8 h/day) or normoxia for 14 days. Hydrogen gas (3.05 vol/100 vol) was administered by inhalation to CM hamsters during hypoxia. After evaluating cardiac function by echocardiography, the heart was examined by light and electron microscopy, immunohistochemistry and RT-PCR. IH tended to increase the ratio of early diastolic mitral inflow to mitral annulus velocity (E/e', 21.8 vs. 16.9), but did not affect LV ejection fraction (EF) in Syrian hamsters. In CM hamsters, however, IH increased E/e' (29.4 vs. 21.5) and significantly decreased ejection fraction (37.2% vs. 47.2%). IH also increased cardiomyocyte cross-sectional area (672 vs. 443 μm(2)), interstitial fibrosis (29.9% vs. 9.6 %), associated with increased oxidative stress and superoxide production in LV myocardium. Furthermore, IH significantly increased c-fos and c-jun mRNA expression in CM. Hydrogen gas inhalation significantly decreased oxidative stress and embryonic gene expression, consequently preserving cardiac function in CM hamsters. IH accelerated LV remodeling of failing heart at least partly through increased oxidative stress in CM hamsters, which might account for the poor prognosis of patients with HF accompanied by sleep apnea.