Am J Physiol Heart Circ Physiol 301: H1062–H1069, 2011.
First published June 3, 2011; doi:10.1152/ajpheart.00150.2011.
Inhalation of hydrogen gas attenuates left ventricular remodeling induced
by intermittent hypoxia in mice
Tetsuya Hayashi,1,2 Toshitaka Yoshioka,3 Kenichi Hasegawa,3 Masatoshi Miyamura,1 Tatsuhiko Mori,1
Akira Ukimura,1 Yasuo Matsumura,3 and Nobukazu Ishizaka1
1
Faculty of Medicine, Department of Internal Medicine III, Takatsuki; Medical College, Takatsuki; 2Clinical Research Center,
Osaka Medical College Hospital, Osaka; and 3Laboratory of Pathological and Molecular Pharmacology, Osaka University of
Pharmaceutical Sciences, Takatsuki, Japan
Submitted 14 February 2011; accepted in final form 20 May 2011
intermittent hypoxia; cardiac remodeling; oxidative stress; hydrogen
gas
SLEEP APNEA SYNDROME (SAS) is known to increase the risk of
cardiovascular morbidity and mortality (23, 14, 5). A major
feature of SAS is recurrent hypo- and apnea, leading to intermittent hypoxia and the production of reactive oxygen species
(ROS) in various organs and tissues (33, 31, 27, 4). We have
already reported that intermittent hypoxia in mice accelerates
the progression of atherosclerosis and increases nuclear factor␬B-binding activity in the left ventricular (LV) myocardium,
accompanied by cardiomyocyte degeneration and interstitial
fibrosis (17, 34, 8). Oxidative stress may result from an
imbalance between generation and elimination of ROS. The
Address for reprint requests and other correspondence: T. Hayashi, Dept. of
Internal Medicine III, Osaka Medical College, 2-7 Daigakumachi, Takatsuki,
Osaka 569-8686, Japan (e-mail: [email protected]).
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hydroxyl radical is a highly toxic radical that is known to
interact with lipids, proteins, and nucleic acids (20), and it may
play a crucial role in the development of LV remodeling.
Hydrogen (H2) gas is physiologically produced in the large
intestine by intestinal bacteria during the fermentation of nondigestible carbohydrates (3). Recent studies have suggested
that H2 gas may selectively scavenge hydroxyl radicals and
thus exert an antioxidant effect (18). Ohsawa et al. (21)
demonstrated that ingestion of H2-saturated water decreased
oxidative stress and prevented atherosclerosis in apolipoprotein
E knockout mice, whereas inhalation of H2 gas was reported to
have a cardioprotective effect against ischemia-reperfusion
injury in rats (9). However, the effects of H2 gas inhalation on
progression of LV remodeling and alteration of the lipid profile
have not been investigated in an experimental animal model of
SAS. Therefore, we examined H2 gas inhalation using three
different regimens to investigate its effect on lipid abnormalities and LV remodeling induced by intermittent hypoxia in
mice.
MATERIALS AND METHODS
Animals. We used 8-wk-old male C57BL/6J mice (purchased from
Clea Japan, Osaka, Japan) in this study. Animals were kept under a
12:12-h light-dark cycle and were allowed free access to standard
chow and tap water. The study protocol and animal care methods were
approved by the Osaka University of Pharmaceutical Sciences Experimental Animal Research Committee, and all experiments were conducted in accordance with the National Institutes of Health Guidelines
for the Care and Use of Laboratory Animals.
Study protocol. Animals were placed in a chamber and were
exposed to intermittent hypoxia (IH, repetitive cycles of 1 min each
with 5 and 21% oxygen for 8 h during the daytime because mice are
nocturnal animals) with or without administration of H2 gas for seven
consecutive days (n ⫽ 62). Repetitive administration of H2 gas (1.3
vol/100 vol) was done at the time of reoxygenation (H2-reoxy), during
hypoxia (H2-hypo), or throughout the experimental period (H2throughout) (Fig. 1). Each gas was manufactured and mixed by
TAIYO NIPPON SANSO (Tokyo, Japan), and the content was
confirmed by gas chromatography. Mice kept under normoxic conditions in a same room served as controls (n ⫽ 13). Thus a total of five
groups were examined, which were the IH, H2-reoxy, H2-hypo,
H2-throughout, and control groups. At 20 h after the last exposure to
hypoxia, measurement of right ventricular and LV systolic pressures
was performed by cardiac catheterization under anesthesia induced by
intraperitoneal injection of pentobarbital sodium (50 mg/kg). After
blood sampling, the heart was excised, and the upper half cut beneath
the mitral valve level was subjected to light microscopic examination.
The LV free wall myocardium was also excised for electron microscopic examination, immunohistochemistry, and real-time reverse
transcription-polymerase chain reaction (RT-PCR).
0363-6135/11 Copyright © 2011 the American Physiological Society
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Hayashi T, Yoshioka T, Hasegawa K, Miyamura M, Mori T,
Ukimura A, Matsumura Y, Ishizaka N. Inhalation of hydrogen gas
attenuates left ventricular remodeling induced by intermittent hypoxia
in mice. Am J Physiol Heart Circ Physiol 301: H1062–H1069, 2011.
First published June 3, 2011; doi:10.1152/ajpheart.00150.2011.—
Sleep apnea syndrome increases the risk of cardiovascular morbidity
and mortality. We previously reported that intermittent hypoxia increases superoxide production in a manner dependent on nicotinamide
adenine dinucleotide phosphate and accelerates adverse left ventricular (LV) remodeling. Recent studies have suggested that hydrogen
(H2) may have an antioxidant effect by reducing hydroxyl radicals. In
this study, we investigated the effects of H2 gas inhalation on lipid
metabolism and LV remodeling induced by intermittent hypoxia in
mice. Male C57BL/6J mice (n ⫽ 62) were exposed to intermittent
hypoxia (repetitive cycle of 1-min periods of 5 and 21% oxygen for 8
h during daytime) for 7 days. H2 gas (1.3 vol/100 vol) was given
either at the time of reoxygenation, during hypoxic conditions, or
throughout the experimental period. Mice kept under normoxic conditions served as controls (n ⫽ 13). Intermittent hypoxia significantly
increased plasma levels of low- and very low-density cholesterol and
the amount of 4-hydroxy-2-nonenal-modified protein adducts in the
LV myocardium. It also upregulated mRNA expression of tissue
necrosis factor-␣, interleukin-6, and brain natriuretic peptide, increased production of superoxide, and induced cardiomyocyte hypertrophy, nuclear deformity, mitochondrial degeneration, and interstitial
fibrosis. H2 gas inhalation significantly suppressed these changes
induced by intermittent hypoxia. In particular, H2 gas inhaled at the
timing of reoxygenation or throughout the experiment was effective in
preventing dyslipidemia and suppressing superoxide production in the
LV myocardium. These results suggest that inhalation of H2 gas was
effective for reducing oxidative stress and preventing LV remodeling
induced by intermittent hypoxia relevant to sleep apnea.
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H2 GAS AND HYPOXIA-INDUCED LV REMODELING
Measurement of lipid profiles. Plasma lipoproteins were analyzed
using a high-performance liquid chromatography system at Skylight
Biotech (LipoSEARCH, Akita, Japan), according to the protocol
described elsewhere (32). Briefly, the cholesterol concentration in
major lipoproteins and lipoprotein subclasses [from G1 (particle
diameter ⬎80 nm) to G13 (particle diameter ⬎16.7 nm)] was determined by modified Gaussian curve fitting to resolve overlapping
peaks (22).
Measurement of cross-sectional area and histological examination.
Heart tissues were fixed in 10% formaldehyde, embedded in paraffin,
and cut into 4-␮m sections. Photographs sampled by a light microscopy (ECLIPSE 80i; Nikon, Tokyo, Japan) at 1⫻ magnification were
transformed to the binary images, and cardiac cross-sectional area was
evaluated using ImageJ version 1.44 software [National Institutes of
Health (NIH)]. To determine the mean cardiomyocyte diameter, the
shortest diameters of 100 cardiomyocytes in each sample were measured using NIS-Elements version 3.07 software (Nikon), only in
nucleated transverse sections stained with hematoxylin-eosin under a
light microscope at ⫻400 magnification. After staining with Sirius
red, color images were taken from five randomly selected high-power
fields (⫻200), and the percentage of collagen volume was calculated
by the method previously reported (34).
For electron microscopy, part of the LV myocardium was fixed in
4% paraformaldehyde containing 0.25% glutaraldehyde and 4.5%
sucrose. Ultrathin sections obtained from the embedded blocks were
stained with uranyl acetate and lead citrate and examined using an
electron microscope (model H-7650; Hitachi, Tokyo, Japan) (7).
Immunohistochemistry for 4-hydroxy-2-nonenal protein expression.
Immunohistochemical staining was performed to determine the amount
of 4-hydroxy-2-nonenal (4-HNE)-modified protein adducts (8). Briefly,
paraffin sections of the left ventricle were incubated with a monoclonal antibody directed against 4-HNE (product no. MHN-20; Japan
Institute for the Control of Aging, Shizuoka, Japan) and a secondary
antibody (biotinylated anti-mouse IgG), followed by the addition of
Vectastatin Elite ABC reagent (Vector Laboratories, Burlingame,
CA). The percent area of 4-HNE staining was measured by quantitative analysis (16). Results were compared with the mean percent area
of control that was defined 1.0 and expressed as the 4-HNE expression
ratio.
Detection of superoxide in the LV myocardium. To detect the
production of superoxide in situ, freshly frozen unfixed LV specimens
were incubated with 10 ␮mol/l of dihydroethidium (DHE; Molecular
Probes, Eugene, OR) solution for 30 min in a light-protected humidified chamber at 37°C. Sections were then examined using a fluorescence microscope (BZ-8000; KEYENCE, Osaka, Japan). DHE fluorescence intensity was quantified using NIH Image 1.61 software and
compared with the mean intensity of control (17).
Quantitative real-time RT-PCR. Total RNA was extracted from LV
myocardial tissues using an RNeasy Mini Kit (Qiagen, Valencia, CA).
Reverse transcription was performed with random hexamers and
Table 1. Effects of H2 gas inhalation on body weight, heart weight, and hemodynamics
H2 Gas Inhalation
Normoxia
Intermittent Hypoxia
Reoxygenation
Hypoxia
Throughout
n
Body wt, g
Heart wt, mg
Heart wt/body wt, mg/g
13
23.7 ⫾ 0.6
107.2 ⫾ 1.5
4.5 ⫾ 0.1
12
22.5 ⫾ 0.3
116.2 ⫾ 3.1
5.1 ⫾ 0.1*
18
22.1 ⫾ 0.2
107.3 ⫾ 1.6
4.8 ⫾ 0.1
18
21.2 ⫾ 0.2
106.4 ⫾ 2.4
5.0 ⫾ 0.1*
14
22.0 ⫾ 0.3
105.2 ⫾ 2.4#
4.7 ⫾ 0.1
n
RVSP, mmHg
LVSP, mmHg
3
23.7 ⫾ 3.2
106.0 ⫾ 2.1
4
33.5 ⫾ 2.9
108.5 ⫾ 1.8
7
30.4 ⫾ 2.0
99.4 ⫾ 2.4
6
29.2 ⫾ 2.0
110.5 ⫾ 5.2
Hemodynamic parameters
6
32.0 ⫾ 1.3
100.7 ⫾ 4.9
Values are means ⫾ SE; n, no. of animals. Heart wt/body wt, heart weight-to-body weight ratio; RVSP, right ventricular systolic pressure; LVSP, left
ventricular systolic pressure. P ⬍ 0.05 vs. normoxia (*) and vs. intermittent hypoxia (#).
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Fig. 1. Study protocol. The schema shows the timing of hydrogen (H2) gas provision: 1.3 vol/100 vol
of H2 gas given at the time of reoxygenation (H2reoxy) (A), during hypoxia (H2-hypo) (B), or
throughout the experiment (H2-throughout) (C).
During the experiment, oxygen volume percentage
in the chamber was monitored using a Zirconia-type
oxygen analyzer (FUJIKURA, Tokyo, Japan), and
oxygen levels in the chamber of the hypoxic group
are maintained at 21 and 5% alternating.
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H2 GAS AND HYPOXIA-INDUCED LV REMODELING
Fig. 2. Plasma lipoproteins analyzed using highperformance liquid chromatography. Intermittent
hypoxia (Hypoxia) elevated low- and very low-density lipoproteins (LDL and VLDL, respectively) of
plasma cholesterol in mice (□). Inhalation of H2 gas
throughout the experiment (Œ) significantly suppressed the increases in LDL and VLDL. Marks and
bars represent means ⫾ SE. **P ⬍ 0.01 vs. normoxia
(); #P ⬍ 0.05 and ##P ⬍ 0.01 vs. hypoxia.
natriuretic peptide (BNP)] were purchased from Applied Biosystems.
The reaction conditions were as follows: 50°C for 2 min, 95°C for 10
min, then 40 cycles of 95°C for 15 s and 60°C for 1 min. The level of
the target mRNA was normalized to that of GAPDH mRNA (11).
Statistical analysis. Values are means ⫾ SE. For statistical analyses, we used one-way ANOVA followed by Tukey-Kramer multiple-
Fig. 3. Effects of H2 gas on plasma cholesterol subclasses in mice. Fractions from G3 through G10 are shown. Intermittent hypoxia significantly increased each
plasma cholesterol fraction. In fractions G5, G6, G7, G8, G9, and G10, H2-reoxy as well as H2-throughout effectively suppressed the increase in plasma
cholesterol. Values are means ⫾ SE of the no. of animals in parentheses. **P ⬍ 0.01 vs. normoxia; #P ⬍ 0.05 and ##P ⬍ 0.01 vs. intermittent hypoxia.
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Superscript reverse transcriptase (Invitrogen, Carlsbad, CA). RTPCR was performed using an ABI Step One sequence detector (PE
Applied Biosystems, Foster City, CA). Taqman Probe and primers
for the endogenous control mRNA (Ma99999915 for GAPDH) and
the target mRNA [Ma00443258 for tumor necrosis factor-␣ (TNF-␣),
Ma00446191 for interleukin-6 (IL-6), and Ma00435304 for brain
H2 GAS AND HYPOXIA-INDUCED LV REMODELING
comparison tests. A probability (P) value of ⬍0.05 was taken as
indicating statistical significance.
RESULTS
of irregular mitochondria in the LV myocardium. Ballooning
and loss of cristae in many mitochondria, and myelin-like
figures, were observed occasionally. In the groups with H2 gas
inhalation, especially in the H2-throughout group, the fine
structure of the LV myocardium was well preserved (Fig. 5).
Superoxide production and 4-HNE expression in the LV
myocardium. Superoxide production (detected by DHE labeling) and 4-HNE-modified protein adducts were increased significantly in the LV myocardium of IH mice. Inhalation of H2
gas significantly suppressed superoxide production and 4-HNE
adducts in the LV myocardium (Fig. 6).
RT-PCR. IH significantly increased the expression of
TNF-␣, IL-6, and BNP mRNA in the LV myocardium. Inhalation of H2 gas, regardless of the timing of administration,
significantly reduced the expression of TNF-␣, IL-6, and BNP
mRNA in the LV myocardium (Fig. 7).
DISCUSSION
We demonstrated in the present mouse model that inhalation
of H2 gas at low concentrations (1.3 vol/100 vol) reduced
IH-induced dyslipidemia when done at the time of reoxygenation and also prevented cardiomyocyte hypertrophy and
perivascular fibrosis in the LV myocardium. Although H2 is
reported to have no risk of igniting at concentrations of ⬍4%
(19), we only used 1.3 vol/100 vol H2 (the highest concentra-
Fig. 4. Representative light micrographs and quantitative measurement of cardiac cross-sectional area, cardiomyocyte diameter, and percentage of collagen
(%fibrosis) in the left ventricular (LV) myocardium. Intermittent hypoxia caused cardiac hypertrophy (D), and cardiomyocyte degeneration (E) and increased
perivascular fibrosis (F) in the LV myocardium, effects that were suppressed by H2 gas inhalation, especially in the H2-throughout group (G⫺I). Quantitatively,
intermittent hypoxia significantly increased the cardiac cross-sectional area, the mean cardiomyocyte diameter, and perivascular fibrosis. Inhalation of H2 gas
significantly suppressed these changes. Values are means ⫾ SE of the no. of animals in parentheses. ***P ⬍ 0.001 vs. normoxia; #P ⬍ 0.05 and ###P ⬍ 0.001
vs. intermittent hypoxia.
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Body weight, heart weight, and hemodynamics. The heartto-body weight ratio was increased significantly in IH and
H2-hypo. H2-throughout significantly decreased the heart
weight compared with IH (Table 1). No significant differences
of right ventricular and LV systolic pressures were seen among
the five groups.
Plasma cholesterol lipoprotein profile. IH significantly increased plasma levels of low- and very low-density cholesterol
lipoproteins (LDL-C and VLDL-C, respectively) (Fig. 2). In
fractions G5–G10, H2-reoxy and H2-throughout significantly
suppressed the increase of LDL-C and VLDL-C caused by IH
(Fig. 3). There were no significant changes of high-density
lipoprotein cholesterol.
Histological findings. Light microscopy revealed that IH
significantly increased the cardiac cross-sectional area, the
cardiomyocyte diameter, and the percentage of perivascular
fibrosis in the LV myocardium. These changes were suppressed significantly by inhalation of H2 gas. H2-throughout
was more effective in reducing cardiac cross-sectional area
than H2-reoxy and in preventing cardiomyocyte hypertrophy
than H2-reoxy and H2-hypo (Fig. 4). Electron microscopy
showed that IH increased nuclear invagination and the number
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H2 GAS AND HYPOXIA-INDUCED LV REMODELING
Fig. 6. Dihydroethidium (DHE) labeling
(A⫺C) and immunohistochemistry for 4-hydroxy-2-nonenal (4-HNE) (D⫺F) in the LV
myocardium. Increased superoxide production
(B) and oxidative stress (E) were observed in
mice exposed to intermittent hypoxic stress,
which effects were suppressed by H2 gas inhalation (C and F). Quantitatively, intermittent
hypoxia significantly increased superoxide production and 4-HNE-modified protein adducts in
the LV myocardium, whereas these changes
were suppressed significantly by H2 gas. Suppression of superoxide production by H2 gas was
greater in the H2-throughout group than the H2hypo group. Values are means ⫾ SE of the no.
of animals in parentheses. ***P ⬍ 0.001 vs.
normoxia; #P ⬍ 0.05, ##P ⬍ 0.01, and ###P ⬍
0.001 vs. hypoxia.
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Fig. 5. Representative electron micrograph of
the LV myocardium. Compared with the control group kept under normoxic conditions (A),
intermittent hypoxia increased the no. of small
and bizarre-shaped mitochondria (Mt) and deformity of nuclei (N) (white arrow) in the LV
myocardium (B). Ballooning and loss of cristae of mitochondria and myelin-like figure
(arrow) were observed in a myocardial cell
judging from the basement membrane (arrowheads) and myofilaments (C). In the groups
with H2 gas inhalation, especially in the H2throughout group, the fine structure of the LV
myocardium was well preserved, and lipofuscin and lysosomes were not increased (D). The
scale bar indicates 1 ␮m.
H2 GAS AND HYPOXIA-INDUCED LV REMODELING
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tion allowed for transportation of mixed oxygen/hydrogen gas
under Japanese law).
IH relevant to SAS is known to cause dyslipidemia and
increase oxidative stress, and SAS has been reported as a
risk factor for cardiovascular disease (29, 27). There is
increasing evidence that IH is independently associated with
dyslipidemia (27, 4). However, the precise mechanisms by
which IH induces dyslipidemia are not clear. Free radicals
may be involved in the production of oxidized cholesterol
(6). Li et al. (15) reported that IH, similar to that used in our
experiment, for 5 days increased sterol regulatory elementbinding protein-1 and stearoyl-CoA desaturase-1 in the liver
of lean mice and also increased fasting serum total cholesterol and triglycerides, with a very small LDL-C peak
detected by high-performance liquid chromatography. The
increased levels of oxidized LDL in their study may have
been related to IH-induced changes of hepatic lipid biosynthesis and cholesterol uptake (4). We also found that IH
significantly increased VLDL-C and LDL-C, which was
suppressed by H2 inhalation. Intriguingly, H2 gas given at
the timing of reoxygenation (H2-reoxy) significantly suppressed increases in VLDL-C and LDL-C (cholesterol fractions G5–G10) induced by IH. These results suggest that
radical scavenging by H2 gas is useful in normalizing lipid
metabolism in the liver under hypoxic stress (30). Persistent
dyslipidemia might exacerbate cardiovascular remodeling
induced by hypoxic stress. Further studies, with longer
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observation periods, are required to clarify the effects of H2
inhalation on cholesterol uptake in the liver.
Oxidative stress plays an important role in the progression of
cardiovascular disease (25). In this study, superoxide production and 4-HNE-modified protein adducts in the LV myocardium were increased by intermittent hypoxic stress, whereas
these changes were inhibited by 1.3 vol/100 vol H2 gas. It may
be that H2 gas reduces oxidative stress by scavenging free
radicals. The present study suggested that inhalation of H2 gas
suppresses oxidative stress and prevents IH-induced LV remodeling. Ohsawa et al. (20) showed that H2 protects cells and
tissues against strong oxidative stress by scavenging the hydroxyl radical. It is also possible that H2 gas protects against
oxidative stress by reducing other strong oxidant species in
living cells. It was reported that H2 prevents a decrease in
cellular levels of ATP synthesized in mitochondria (20). Our
electron microscopy study demonstrated that inhalation of H2
gas decreased the number of degenerated mitochondria and
preserved the fine structure of the LV myocardium. Although
the reason why giving H2 gas throughout the experiment
(H2-throughout) was more effective in preserving the cardiomyocyte diameter and reducing heart weight than intermittently administered H2 gas (H2-reoxy and H2-hypo) is unclear,
the concentration of H2 gas may be important for histological
protection.
Recently, inhalation of 2% hydrogen was reported to reduce
inflammatory mediators, such as IL-1␤, IL-6, and TNF-␣ (1).
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Fig. 7. Quantitative RT-PCR. Representative blots of GAPDH show that GAPDH as a housekeeping gene was not affected by intermittent hypoxia.
Intermittent hypoxia significantly increased expression of tumor necrosis factor (TNF)-␣, interleukin (IL)-6, and brain natriuretic peptide (BNP) mRNA
in the LV myocardium. Inhalation of H2 gas significantly reduced cytokine expression in the LV myocardium. Although H2-throughout tended to suppress
TNF-␣ and BNP mRNA most effectively, no statistical differences were seen between the 3 H2 gas groups. Values are means ⫾ SE of the no. of animals
in parentheses. **P ⬍ 0.01 vs. normoxia; ##P ⬍ 0.01 vs. hypoxia.
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H2 GAS AND HYPOXIA-INDUCED LV REMODELING
ACKNOWLEDGMENTS
We express our gratitude to Y. Ogami, Y. Mizuoka, C. Ota, M. Ito, and M.
Kobayashi for expert technical assistance. We also thank Skylight Biotech for
technical assistance.
GRANTS
This study was supported by Kakenhi (23590267), a Grant-in-Aid for
Scientific Research from the Japanese Ministry of Education, Culture, Sports,
Science and Technology, and an Osaka Medical College Research Fund.
DISCLOSURES
None.
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IH is known to increase C-reactive protein and activate various
inflammatory cells, which have been implicated in the development of atherosclerotic lesions (13, 26, 24). We have previously reported that IH (30 s of 4.5–5.5% O2 followed by 30 s
of 21% O2 for 8 h/day during the daytime for 10 days)
increased TNF-␣ and IL-6 mRNA levels in the LV myocardium, changes that were possibly related to hypoxia-induced
LV remodeling (8). We also reported that continuous hypoxia
(10% O2 for 14 days) increased hypoxia-inducible factor-1␣
and vascular endothelial growth factor in the rat myocardium
(10), although interstitial fibrosis was not increased, which had
been reported by Sharma et al. (28). Transforming growth
factor-␤ should be examined to evaluate the effect of hypoxia on interstitial fibrosis. Recently, Casals et al. (2)
reported that hypoxia (5% O2) induces the synthesis and
secretion of BNP in human cultured ventricular myocytes.
In this study, IH (repetitive cycle of 1-min periods of 5 and
21% oxygen level for 8 h/day during the daytime for 7 days)
increased TNF-␣, IL-6, and BNP mRNA expression in the
LV myocardium, which effects were significantly suppressed by inhalation of 1.3 vol/100 vol H2 gas, regardless
of the timing of administration. Taken together with the
histological findings, H2 gas given throughout the experimental period exhibited the greatest cardioprotective effects
of the three different methods of H2 gas administration.
These effects differed somewhat from the effects of H2 gas
on dyslipidemia, so further studies are required.
In conclusion, H2 gas attenuated the development of
IH-induced LV remodeling at least partly through the suppression of oxidative stress. Short-term inhalation of H2 gas
was effective in reducing oxidative stress and in preventing
LV remodeling induced by IH relevant to sleep apnea.
Inhalation of H2 gas during hospitalization might be potentially useful for preventing cardiovascular events in patients
with SAS.
H2 GAS AND HYPOXIA-INDUCED LV REMODELING
AJP-Heart Circ Physiol • VOL
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