title: 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 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.
authors.affiliation: Laboratory of Cardiovascular Pharmacotherapy and Toxicology, Osaka University of Pharmaceutical Sciences, Takatsuki, Japan;
authors.forename: Ryuji
authors.initials: R
authors.lastname: Kato
authors.affiliation: Laboratory of Cardiovascular Pharmacotherapy and Toxicology, Osaka University of Pharmaceutical Sciences, Takatsuki, Japan;
authors.forename: Atsuo
authors.initials: A
authors.lastname: Nomura
authors.affiliation: Laboratory of Vascular Biology, National Cerebral and Cardiovascular Center, Suita, Japan;
authors.forename: Aiji
authors.initials: A
authors.lastname: Sakamoto
authors.affiliation: Laboratory of Cardiovascular Pharmacotherapy and Toxicology, Osaka University of Pharmaceutical Sciences, Takatsuki, Japan;
authors.forename: Yuki
authors.initials: Y
authors.lastname: Yasuda
authors.affiliation: Laboratory of Cardiovascular Pharmacotherapy and Toxicology, Osaka University of Pharmaceutical Sciences, Takatsuki, Japan;
authors.forename: Koyuha
authors.initials: K
authors.lastname: Amatani
authors.affiliation: Laboratory of Cardiovascular Pharmacotherapy and Toxicology, Osaka University of Pharmaceutical Sciences, Takatsuki, Japan;
authors.forename: Sayuri
authors.initials: S
authors.lastname: Nagai
authors.affiliation: Laboratory of Cardiovascular Pharmacotherapy and Toxicology, Osaka University of Pharmaceutical Sciences, Takatsuki, Japan;
authors.forename: Yoko
authors.initials: Y
authors.lastname: Sen
authors.affiliation: Laboratory of Cardiovascular Pharmacotherapy and Toxicology, Osaka University of Pharmaceutical Sciences, Takatsuki, Japan;
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Ijiri
authors.affiliation: Department of Pathology, Osaka Medical College, Daigakumachi, Takatsuki, Japan;
authors.forename: Yoshikatsu
authors.initials: Y
authors.lastname: Okada
authors.affiliation: Department of Cardiovascular Medicine, Osaka City University Graduate School of Medicine, Osaka, Japan; and.
authors.forename: Takehiro
authors.initials: T
authors.lastname: Yamaguchi
authors.affiliation: Department of Pharmacology, Osaka City University Graduate School of Medicine, Osaka, Japan.
authors.forename: Yasukatsu
authors.initials: Y
authors.lastname: Izumi
authors.affiliation: Department of Cardiovascular Medicine, Osaka City University Graduate School of Medicine, Osaka, Japan; and.
authors.forename: Minoru
authors.initials: M
authors.lastname: Yoshiyama
authors.affiliation: Laboratory of Cardiovascular Pharmacotherapy and Toxicology, Osaka University of Pharmaceutical Sciences, Takatsuki, Japan;
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Tanaka
authors.affiliation: Laboratory of Cardiovascular Pharmacotherapy and Toxicology, Osaka University of Pharmaceutical Sciences, Takatsuki, Japan; hayashi@gly.oups.ac.jp.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Hayashi
mesh_terms: D000447:Aldehydes / Q000494:pharmacology; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D009202:Cardiomyopathies / Q000000981:diagnostic imaging / Q000235:genetics / Q000473:pathology*; D006224:Cricetinae; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D005740:Gases; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects*; D006352:Heart Ventricles / Q000187:drug effects; D006859:Hydrogen / Q000494:pharmacology*; D000860:Hypoxia / Q000473:pathology*; D008647:Mesocricetus; D009929:Organ Size / Q000187:drug effects; D013481:Superoxides / Q000378:metabolism; D014463:Ultrasonography; D020257:Ventricular Remodeling / Q000187:drug effects*
chemical_list: D000447:Aldehydes; D015853:Cysteine Proteinase Inhibitors; D005740:Gases; D013481:Superoxides; D006859:Hydrogen; C027576:4-hydroxy-2-nonenal
keywords: cardiomyopathic hamster; heart failure; hydrogen gas; intermittent hypoxia; oxidative stress