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

Abstract

T. Hydrogen gas attenuates embryonic gene expression and prevents left ventricular remodeling induced by intermittent hypoxia in cardiomyopathic hamsters. Am J Physiol Heart Circ Physiol 307: H1626 -H1633, 2014. First published October 3, 2014; doi:10.1152/ajpheart.00228.2014.-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 ϭ 22) and cardiomyopathic (CM) hamsters (n ϭ 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 m 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, ␤-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. heart failure; intermittent hypoxia; oxidative stress; cardiomyopathic hamster; hydrogen gas SLEEP APNEA SYNDROME (SAS) is a breathing disorder characterized by recurrent episodes of apnea and/or hypopnea that increases the risk of cardiovascular morbidity and mortality (10,19,26). In persons with SAS, recurrent hypopnea/apnea leads to intermittent hypoxia (IH). The prevalence of SAS is much higher in patients with established cardiovascular disease, and central sleep apnea is associated with the more severe forms of heart failure (17), although the mechanisms underlying periodic breathing in patients with heart failure (HF) are complex and multifactorial.Oxidative stress arises because of an imbalance between free radical production and endogenous antioxidant defenses and is increased in patients with HF (4). Free radicals have also been linked to endothelial dysfunction and increased sympathetic tone (2, 16), whereas intravenous infusion of antioxidants reduces free radical levels and attenuates sympathetic activity in animal models of HF (32). It has been suggested that hydrogen gas produced in the large intestine by intestinal bacteria might scavenge hydroxyl radicals (6), and it was recen...

Hydrogen (H2) Inhibits Isoproterenol-Induced Cardiac Hypertrophy via Antioxidative Pathways

“…H 2 inhalation attenuates intermittent hypoxia (Hayashi et al, 2011; Kato et al, 2014), or ischemia/reperfusion (Hayashida et al, 2008), or germinal matrix hemorrhage-induced left ventricular remodeling (Lekic et al, 2011). Drinking H 2 -rich water blocks cardiac fibrosis induced by left kidney artery ischemia/reperfusion injury (Zhu et al, 2011).…”

“…Moreover, H 2 also has important role in protecting against heart diseases. Inhalation of H 2 attenuates left ventricular remodeling induced by intermittent hypoxia (Hayashi et al, 2011; Kato et al, 2014), and improves cardiac hypertrophy after germinal matrix hemorrhage in neonatal rats (Lekic et al, 2011). However, the effects of H 2 on cardiac hypertrophy induced by β-adrenoceptor stimulation and the related signaling mechanisms still remain unclear.…”

Biological signaling by small inorganic molecules

“…Inhalation of H 2 by cardiomyopathic hamsters decreased oxidative stress and attenuated embryonic gene expression under hypoxic conditions [370]. This effect was also demonstrated in a rat model of myocardial ischemia-reperfusion injury [371].…”

Cardiovascular protection by ezetimibe and influence on oxidative stress in mice exposed to intermittent hypoxia

“…It is known that the prevalence of sleep-related breathing disorders is high in patients with cardiovascular disease and obstructive sleep apnea is common in obese patients with atherosclerosis (Gottlieb et al, 2010). Recently, sleep apnea syndrome has been recognized as an independent risk factor of cardiovascular events, and it has been reported that intermittent hypoxia due to sleep apnea might accelerate cardiac remodeling (Nishioka et al, 2013;Kato R et al, 2014). Although reducing the LDL-cholesterol level may decrease cardiovascular events, there are still residual risks including the complication of sleep apnea syndrome (Kubo et al, 2003;Baigent et al, 2005;Gottlieb et al, 2010).…”