doi:10.1152/japplphysiol.01193.2003 97:843-851, 2004.

First published 7 May 2004; J Appl Physiol

Sadayoshi Taguchi
Takeshi Hashimoto, Naoshige Kambara, Ryuji Nohara, Masayuki Yazawa and
after exercise training in myocardial-infarcted rats
and MCT1 in cardiac muscle Expression of MHC-
You might find this additional info useful...
62 articles, 36 of which can be accessed free at: This article cites
/content/97/3/843.full.html#ref-list-1
4 other HighWire hosted articles This article has been cited by

[PDF] [Full Text] [Abstract]

, August 15, 2005; 567 (1): 121-129. J Physiol
Takeshi Hashimoto, Shinya Masuda, Sadayoshi Taguchi and George A Brooks
muscle
Immunohistochemical analysis of MCT1, MCT2 and MCT4 expression in rat plantaris

[PDF] [Full Text] [Abstract]

, April 13, 2007; 100 (7): 1079-1088. Circulation Research
Duncker
Schuurbiers, Rini de Crom, Ger J.M. Stienen, Karin R. Sipido, Jos M.J. Lamers and Dirk J.
Biesmans, Nicky M. Boontje, Dick H.W. Dekkers, Kees Schoonderwoerd, Hans C.H.
Monique C. de Waard, Jolanda van der Velden, Virginie Bito, Semir Ozdemir, Liesbeth
Ventricular Pump Dysfunction in Mice With a Large Myocardial Infarction
Early Exercise Training Normalizes Myofilament Function and Attenuates Left

[PDF] [Full Text] [Abstract]

, May 28, 2010; 285 (22): 16942-16950. J. Biol. Chem.
Jangamreddy and Kristin Swan
Michael P. Czubryt, Lise Lamoureux, Angela Ramjiawan, Bernard Abrenica, Jaganmohan
Expression by ZAC1 Glut4 Regulation of Cardiomyocyte

[PDF] [Full Text] [Abstract]

, December 1, 2013; 305 (11): E1339-E1347. Am J Physiol Endocrinol Metab
Ira J. Goldberg
Aalap Chokshi, Ruiping Ji, Shuiqing Yu, Sunichi Homma, P. Christian Schulze, Rong Tian and
Raffay S. Khan, Yan Lin, Yunying Hu, Ni-Huiping Son, Kalyani G. Bharadwaj, Carla Palacios,
heart metabolism and function
Rescue of heart lipoprotein lipase-knockout mice confirms a role for triglyceride in optimal
including high resolution figures, can be found at: Updated information and services
/content/97/3/843.full.html
can be found at: Journal of Applied Physiology about Additional material and information
http://www.the-aps.org/publications/jappl
This information is current as of April 30, 2014.

ISSN: 0363-6143, ESSN: 1522-1563. Visit our website at http://www.the-aps.org/.

Physiological Society, 9650 Rockville Pike, Bethesda MD 20814-3991. Copyright 2004 by the American Physiological Society.
those papers emphasizing adaptive and integrative mechanisms. It is published 12 times a year (monthly) by the American
publishes original papers that deal with diverse areas of research in applied physiology, especially Journal of Applied Physiology
o
n

A
p
r
i
l

3
0
,

2
0
1
4
D
o
w
n
l
o
a
d
e
d

f
r
o
m

o
n

A
p
r
i
l

3
0
,

2
0
1
4
D
o
w
n
l
o
a
d
e
d

f
r
o
m

Expression of MHC- and MCT1 in cardiac muscle after
exercise training in myocardial-infarcted rats
Takeshi Hashimoto,
1
Naoshige Kambara,
2
Ryuji Nohara,
3
Masayuki Yazawa,
1
and Sadayoshi Taguchi
1
1
Department of Environmental Physiology, Graduate School of Human and Environmental Studies, and
2
Department
of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Sakyo-ku, Kyoto 606-8501;
and
3
Division of Cardiology, Department of Medicine, Kitano Hospital, Osaka 530-8480, Japan
Submitted 7 November 2003; accepted in nal form 3 May 2004
Hashimoto, Takeshi, Naoshige Kambara, Ryuji Nohara, Mas-
ayuki Yazawa, and Sadayoshi Taguchi. Expression of MHC- and
MCT1 in cardiac muscle after exercise training in myocardial-in-
farcted rats. J Appl Physiol 97: 843851, 2004. First published May
7, 2004; 10.1152/japplphysiol.01193.2003.To evaluate the hypoth-
esis that increasing the potential for glycolytic metabolism would
benet the functioning of infarcted myocardium, we investigated
whether mild exercise training would increase the activities of oxida-
tive enzymes, expression of carbohydrate-related transport proteins
(monocarboxylate transporter MCT1 and glucose transporter
GLUT4), and myosin heavy chain (MHC) isoforms. Myocardial
infarction (MI) was produced by occluding the proximal left coronary
artery in rat hearts for 30 min. After the rats performed 6 wk of run
training on a treadmill, the wall of the left ventricle was dissected and
divided into the anterior wall (AW; infarcted region) and posterior
wall (PW; noninfarcted region). MI impaired citrate synthase and
3-hydroxyacyl-CoA dehydrogenase activities in the AW (P 0.01)
but not in the noninfarcted PW. No differences in the expression of
MCT1 were found in either tissues of AW and PW after MI, whereas
exercise training signicantly increased the MCT1 expression in all
conditions, except AW in the MI rats. Exercise training resulted in an
increased expression of GLUT4 protein in the AW in the sham rats
and in the PW in the MI rats. The relative amount of MHC- was
signicantly increased in the AW and PW in MI rats compared with
sham rats. However, exercise training resulted in a signicant increase
of MHC- expression in both AW and PW in both sham and MI rats
(P 0.01). These ndings suggest that mild exercise training en-
hanced the potential for glycolytic metabolism and ATPase activity of
the myocardium, even in the MI rats, ensuring a benecial role in the
remodeling of the heart.
ischemic heart; mild exercise training; reperfusion; infarcted region;
myosin heavy chain; monocarboxylate transporter; myocardial infarc-
tion
IN FAILING HEARTS, CARDIAC metabolism becomes more depen-
dent on glucose and lactate as respiratory substrates, whereas
fatty acids are the major energy source in healthy and well-
perfused cardiac muscle (1, 31, 52). In failing tissues, glucose
and lactate are readily transported into the cell to be oxidized.
Several studies have reported that lactate and pyruvate were
carried across the cell membrane by monocarboxylate trans-
porters (MCTs) (5, 9, 18, 32). MCT1 is abundant in mitochon-
drial and cell membrane fractions of cardiac muscle high in
oxidative capacity (6, 10). Lactate uptake was signicantly
increased in the moderately trained rat hearts in which MCT1
expression was increased (3). Furthermore, Brooks et al. (11)
reported the presence of lactate dehydrogenase 5 in mitochon-
dria of the left ventricle (LV), suggesting lactate oxidation in
mitochondria. Although it is controversial whether lactate is
oxidized to pyruvate mainly in the cytosol or in the mitochon-
dria, it was considered that MCT1 expression is associated
with an increased oxidation of lactate, which may be benecial
to the failing heart. In fact, a previous study showed an
increased expression of MCT1 in surviving myocardium after
myocardial infarction (MI) in rat (31).
In another biochemical adaptation after MI, pressure over-
load on the surviving myocardium is known to increase the
expression of myosin heavy chain (MHC)- isoform during the
process of left ventricular (LV) remodeling, whereas MHC-
isoform was predominantly expressed in the control rat hearts
(38, 46, 63). This shift of MHC isoform improved myocardial
work efciency but impaired cardiac contractile system
ATPase activity (2, 27, 30). Our laboratory previously sug-
gested that the increase in the expression of MHC- in hy-
poxia-induced hypertrophied ventricles was an adaptive com-
pensation necessary to sustain cardiac contractile efciency in
response to an impairment in oxidative metabolism of the
ventricles in rats (24). In contrast, contractile systems that
possess higher myosin ATPase activities are capable of greater
power outputs, but they consume more ATP to maintain the
same level of force (39, 57). Thus an adequate expression of
MHC- based on the steady state of energy metabolism would
benet the functioning of the cardiac contractile system.
Exercise training is thought to be the only known biological
stressor that produces uniformly positive central and peripheral
cardiovascular adaptations (39). As a potential for glycolytic
metabolism, it was considered that exercise training increased
MCT1 in the cardiac muscle at a lower training intensity than
in skeletal muscle (3, 5). Thus even mild exercise training may
lead to biochemical benets in MCT1 expression, which would
increase lactate uptake in animal myocardium with LV dys-
function. However, the effect of exercise training on the
expression of MCT1 remains unclear in the failing heart. We
hypothesized that mild-intensity exercise training would in-
crease the activities of oxidative enzymes and expressions of
carbohydrate-related transport proteins (MCT1 and glucose
transporter GLUT4) in myocardium of the MI rats. Exercise
training may, therefore, ensure an increased expression of
MHC- necessary to improve cardiac contractile function.
Our laboratory has previously demonstrated that oxidative
enzyme activities of the infarcted myocardium were signi-
Address for reprint requests and other correspondence: S. Taguchi, Dept. of
Environmental Physiology, Graduate School of Human and Environmental
Studies, Kyoto University, Yoshida, Sakyo-Ku, Kyoto 606-8501, Japan
(E-mail: sadataguchi@mct1.mbox.media.kyoto-u.ac.jp).
The costs of publication of this article were defrayed in part by the payment
of page charges. The article must therefore be hereby marked advertisement
in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
J Appl Physiol 97: 843851, 2004.
First published May 7, 2004; 10.1152/japplphysiol.01193.2003.
8750-7587/04 $5.00 Copyright 2004 the American Physiological Society http://www. jap.org 843
o
n

A
p
r
i
l

3
0
,

2
0
1
4
D
o
w
n
l
o
a
d
e
d

f
r
o
m

cantly less than those of the noninfarcted myocardium in the
same LV (26). Rosenblatt-Velin et al. (50) have shown re-
gional differences in the regulatory proteins of metabolism in
postinfarcted heart. In addition, the adenylyl cyclase activity
was decreased in the infarcted LV and increased in the right
ventricle (RV), suggesting a compensatory role of the RV in
failing heart in MI rats (55). In contrast, little is known about
the regional biochemical responses of the LV to exercise
training after MI. We hypothesized that the noninfarcted myo-
cardium would compensate for the infarcted myocardium in
terms of the contractile role of the LV in response to exercise
training. The purpose of this study was to investigate the
effects of mild-intensity exercise training on the expression of
cardiac MCT1 and GLUT4 and MHC isoforms in both in-
farcted and noninfarcted regions of the LV after surgically
induced anterior myocardial ischemia in rats.
METHODS
Animals, care, and experimental groups. Male Wistar-Kyoto rats (8
wk of age, 250 10 g) were randomly assigned to four groups: 1)
sedentary sham (SS; n 5), 2) sedentary MI (SMI, n 7), 3) exercise
sham (ES; n 6); and 4) exercise MI (EMI; n 8). All rats were
housed in a temperature-controlled environment (22 1C) with a
12:12-h light-dark cycle and fed ad libitum. These experiments
conrmed with the Guiding Principle for the Care and Use of Animals
approved by the Council of the Physiological Society of Japan.
Operation to create MI. In MI-operated groups, myocardial ische-
mia was surgically induced in accordance with a previous study by
occluding the left coronary artery near its origin with a 6-0 silk suture
for 30 min while the rats were anesthetized with pentobarbital sodium
(40 mg/kg), and then they were reperfused (25). In the sham-operation
groups, only a left thoracotomy was performed without left coronary
artery occlusion. Each animal was allowed 4 wk of recovery from the
operation before the training regimen commenced. Animals were
maintained on standard chow and water ad libitum.
Exercise training protocol. After a 4-wk recovery period, the
exercise training groups ran at 10 m/min for 60 min/day, 5 days per
week, for 6 wk on a motor-driven wheel treadmill (1.57 m in
circumference).
Before and after the exercise training program, transthoratic echo-
cardiography was performed to assess LV dimension, LV anterior
wall (AW) and posterior wall (PW) thickness at end diastole, and
stroke volume by using an echo Doppler system (model SSA-380A,
Toshiba, Tochigi-Ken, Japan) with a 7.5-MHz transducer. In addition,
heart rate was measured, and cardiac output was calculated as cardiac
output stroke volume heart rate. The details of this measurement
are described in a previous study (26).
Tissue sampling. After the echocardiographic measurement follow-
ing 6 wk of the exercise training program, all animals were anesthe-
tized with pentobarbital sodium (50 mg/kg). With the rats under
ventilation with a rodent respirator, their whole hearts were isolated,
and immediately tissue wet weights were obtained. The atria were
trimmed from the base of the ventricles, and the RV was dissected at
its juncture with the septal wall. The LV was divided into two sections
according to single-photon-emission computed tomography (SPECT)
imaging: AW as the ischemic region and PW as the nonischemic
region (26). Both walls were immediately frozen in liquid nitrogen
and stored at 80C until biochemical assays. In the pinhole SPECT
system, myocardial perfusion and fatty acid metabolism were assessed
with thallium-201 (
201
Tl) and iodine-123-labeled 15-(p-iodophenyl)-
3-(R,S)-methylpentadecanoic acid (BMIPP), respectively, which were
injected via the femoral vein. BMIPP uptake reects exogenous fatty
acid utilization in the myocardium but not -oxidation of fatty acids
(33). To assess the
201
Tl chloride and BMIPP uptake, the serial
myocardial images were divided into 20 segments as previously
described (26). Each segment was then separated according to a
modied semiquantitative 4-point scoring system: 0 normal uptake,
1 slightly (25%) reduced uptake, 2 moderately (50%)
reduced uptake, 3 severely (50%) reduced uptake. In the MI groups,
the difference between
201
Tl chloride severity score and BMIPP
severity score was dened as the mismatch score (mismatch score
BMIPP severity score
201
Tl chloride severity score). We identied
the ischemic region (AW) as a mismatch portion with a score 3 (Fig.
1). The PW was identied as the nonischemic region. The SPECT
imaging procedure was in accordance with previous studies (12, 26).
Electrophoretic analysis. Sodium dodecyl sulfate-polyacrylamide
gel electrophoresis (SDS-PAGE) was used for separating the cardiac
MHC isoforms, MHC- and MHC- (24). Frozen samples were
homogenized and diluted 1:500 in buffer (35). These samples were
heated at 80C for 5 min before the gels were loaded, 2 l per lane.
The preparation and composition of the gels were identical to those
described by Talmadge and Roy (60), except that the stacking and
separating gels (0.75 mm thick) included 10% (vol/vol) glycerol.
Separate upper and lower running buffers were identical to those in
the study of Reiser and Kline (49). Gels were run at a constant voltage
of 200 V for 35 h (Bio-Rad Protein II xi Cell electrophoretic system
utilizing a Bio-Rad PowerPac 1000 power supply) in a chamber
controlled at 4C. After separation, the gels were stained with Coo-
massie blue and scanned by using a laser densitometer equipped with
an integrator (Multi-Analyst, Bio-Rad). Densitometric scans of single
gel lanes contain both isoforms of cardiac MHC. MHC- migrates
further than MHC- in rats as well as in any other species (49).
Muscle enzyme assays. The enzyme activities were determined
from 5% homogenates of tissue in 175 mM KCl, 10 mM GSH, and 2
mM EDTA, pH 7.4. The homogenates were frozen and thawed several
times to disrupt the mitochondrial membrane. Citrate synthase (CS)
activity was measured by spectrophotometry on the supernatant frac-
tion by a modied method of Srere (56). Briey, homogenate was
added to 70 mM Tris buffer, 0.1 mM DTNB, 0.3 mM acetyl-CoA, and
0.5 mM oxaloacetate and read for 5 min at 412 nm. 3-Hydroxyacyl-
CoA dehydrogenase (HAD) was uorimetrically determined by a
modied method of Bass et al. (4). Briey, homogenate was added to
the reaction mixture of 88.3 mM Tris buffer with 4.4 mM EDTA, 75
M NADH, and 0.1 mM acetoacetyl-CoA and read for 5 min at 340
nm. Enzymatic activities were expressed as micromoles of substrate
per minute per gram measured muscle weight.
Western blotting of MCT1 and GLUT-4. MCT1 antibody was a
donation from Dr. H. Hatta (Dept. of Life Science, University of
Tokyo, Tokyo, Japan). GLUT4 antibodies (rabbit anti-GLUT4) were
obtained from Chemicon (Temecula, CA). Sample preparation for
Western blotting was done according to McCullagh et al. (37). The
samples were applied to 12% SDS-polyacrylamide gels. In SDS-
PAGE, the composition of the gels was developed according to
Fig. 1. Thallium-201 (Tl) and iodine-123-labeled 15-(p-iodophenyl)-3-(R,S)-
methylpentadecanoic acid (BMIPP) single-photon-emission computed tomog-
raphy (SPECT) image in myocardial-infarcted (MI) rat after transient ische-
mia. Base means representative of basal ventricular region. Arrows show
decreased uptake of BMIPP in the anterolateral wall, whereas
201
Tl update
reperfused enough.
844 EXERCISE EFFECT ON MHC AND MCT AFTER MI
J Appl Physiol VOL 97 SEPTEMBER 2004 www.jap.org
o
n

A
p
r
i
l

3
0
,

2
0
1
4
D
o
w
n
l
o
a
d
e
d

f
r
o
m

Talmadge and Roy (60) with modications: 1) the acrylamide content
of the separating gel was increased to 12% and 2) the glycerol content
of separating and stacking gels were reduced to 10%. Gels were run
at a constant voltage of 200 V for 2 h (Bio-Rad Mini Protein III Cell
electrophoretic system utilizing a Bio-Rad PowerPac 1000 power
supply) in a chamber controlled at 4C. Western blotting of MCT1
and GLUT4 was done according to previous studies (34, 37). Proteins
were transferred from the gel to the membrane (15 V, 25 min)
(Bio-Rad Trans Blot SD Cell blotting system utilizing a Bio-Rad
PowerPac 200 power supply). Membranes were blocked by 20 mM
Tris HCl, 137 mM NaCl, 0.1% Tween 20, and 10% nonfat dry milk,
pH 7.5, solution for 24 h. Membranes were then incubated with
antibody solution (either MCT1 or GLUT4) for 1 h. After being
washed in 20 mM Tris HCl, 137 mM NaCl, and 0.1% Tween 20, pH
7.5, membranes were incubated with donkey anti-rabbit IgG horse-
radish peroxidase-conjugated secondary antibody (1:7,500; Amer-
sham Biosciences, Piscataway, NJ) in 20 mM Tris HCl, 137 mM
NaCl, and 0.1% Tween 20, pH 7.5. MCT1 and GLUT4 were detected
by using an enhanced chemiluminescence detection method (Amer-
sham Biosciences) by exposing the membrane to lm (Amersham
Biosciences). Band imaging was scanned using laser densitometer
equipped with an integrator (Multi-Analyst, Bio-Rad).
Statistical analysis. Data are expressed as means SE. The
statistical signicance was determined by a two-way analysis of
variance (sedentary/exercise vs. sham/MI), and a Bonferroni test was
used to determine the signicance of difference between means.
Comparisons were made between the AW and the PW of each group
by using a paired t-test. Statistical signicance was considered to be
P 0.05.
RESULTS
LV morphology and function. Table 1 shows the body
weights, heart weights, and LV morphology and function in all
groups. There were no signicant differences in body weights
among the groups. Heart weight was signicantly increased in
MI groups compared with corresponding sham-operated
groups. Furthermore, the heart weight in the EMI group was
higher than that in the SMI group (P 0.01). The LV
dimensions of MI rats were signicantly enlarged compared
with sham rats. There were no signicant differences in wall
thickness among the groups in either AW or PW. In addition,
AW-to-PW thickness ratio was unchanged in each group.
There were no signicant differences in heart rate among the
groups. Exercise enhanced the LV function in terms of in-
creased stroke volume and cardiac output in both Sham and MI
groups.
Oxidative enzyme activities. MI impaired CS and HAD
activities in the AW (A) (P 0.01), but the PW (B) remained
unchanged in both activities (Figs. 2 and 3). In MI rats, CS and
HAD activities in the PW were signicantly higher than those
in the AW. No exercise training effect was observed in oxida-
tive enzyme activities in all conditions studied (Figs. 2 and 3).
MCT1 and GLUT4 expression. MCT1 and GLUT4 protein
expressions were determined by Western blot techniques; rep-
resentative blots are shown in Fig. 4. Figure 5 summarizes the
MCT1 protein contents in both AW (A) and PW (B). No
signicant associations between changes in the expression of
MCT1 and acute MI were observed in both walls (8% increase
in SMI compared with SS in the PW; P 0.05). Compared
with the SS group, the ES group signicantly enhanced the
expression of MCT1 by 38% in the AW and by 65% in the PW
(P 0.05). The expression of MCT1 in the EMI group was
also signicantly higher by 34% than the SMI group (P
Table 1. Body weight, heart weight, and left ventricular morphology and function
Sham MI
Sedentary Exercise Sedentary Exercise
Body weight, g 3739 35510 3688 3607
Heart weight, g 0.800.03 0.960.02 0.990.03* 1.120.02
LV dimension, mm 6.130.12 6.480.14 7.400.32 7.610.26
AW thickness, mm 1.660.05 1.620.06 1.400.10 1.650.11
PW thickness, mm 1.830.07 1.830.09 1.740.08 1.830.09
AW-to-PW thickness ratio 0.920.05 0.900.05 0.810.08 0.940.10
Heart rate, beats/min 45811 4496 42021 42815
Stroke volume, ml/beat 0.190.02 0.250.02 0.210.01 0.250.02
Cardiac output, ml/min 88.317.45 112.447.70 85.695.86 104.896.86
Values are means SE. MI, myocardial infarction; LV, left ventricle; AW, anterior wall; PW, posterier wall. *P 0.05, P 0.01 vs. corresponding
sham-operated group. P 0.05; P 0.01 vs. corresponding sedentary group.
Fig. 2. Citrate synthase (CS) activities in anterior (AW; A) and posterior walls
(PW; B) of the left ventricle. Values are means SE. **P 0.01 vs.
corresponding sham-operated group.
##
P 0.01, AW vs. PW.
845 EXERCISE EFFECT ON MHC AND MCT AFTER MI
J Appl Physiol VOL 97 SEPTEMBER 2004 www.jap.org
o
n

A
p
r
i
l

3
0
,

2
0
1
4
D
o
w
n
l
o
a
d
e
d

f
r
o
m

0.05). However, in the MI group in AW, exercise did not
increase the MCT1 content. In the EMI group, the expression
of MCT1 in the PW was signicantly higher than that in the
AW (P 0.05). Figure 6 summarizes the GLUT4 protein
contents in both AW (A) and PW (B). Exercise training
enhanced the expression of GLUT4. The GLUT4 expression
was signicantly higher in the AW for the ES group than that
of the SS group and in the PW for the EMI group than that of
the SMI group (P 0.01 and P 0.05, respectively). The
GLUT4 expression was signicantly lower in the AW for the
EMI group than that of the ES group (P 0.01). In the EMI
group, the expression of GLUT4 in the PW was signicantly
higher than that in the AW (P 0.05).
MHC isoforms expression. Representative separations of
MHC- and MHC- are shown in Fig. 7. MI group showed a
large percentage of shifts in MHC- in both AW (A) and PW
(B) compared with sham-operated groups (P 0.01; Fig. 8).
On the other hand, exercise training induced a signicant
reduction of MHC- expression in both AW and PW, concom-
itantly indicating an increased MHC- expression (P 0.01;
Fig. 8). In the SMI and EMI groups, the expression of MHC-
in the PW was signicantly higher than that in the AW (P
0.01 and P 0.05, respectively).
Figure 9 shows the ratio of MHC- expression in the AW
vs. PW in both sedentary and exercise sham and MI groups.
Both exercise training and MI decreased relative expression of
MHC- in the PW compared with the AW. In the EMI group,
a large expression of MHC- was observed in the AW com-
pared with the PW.
DISCUSSION
Our present study used a mild-intensity exercise training
program, because an intense exercise program might be poten-
tially harmful in animals with LV dysfunction (17, 41). In
connection to this, Orenstein et al. (46) suggested that one of
the factors accounting for more favorable ventricular remod-
eling was a normalization of the wall tension due to a reduced
cavity volume and an increased wall thickness after exercise
training. However, there was no signicant difference in mor-
phological changes in dimensions and ventricular walls of both
sham and MI rats, although stroke volume and cardiac output
increased after exercise training (Table 1).
Our results revealed that surgically induced MI in the sed-
entary rats impaired CS and HAD activities in the AW but not
in the PW. These ndings were consistent with previous
studies (26, 44). There was no change in oxidative enzyme
activities (CS and HAD) in ventricular wall tissues after
exercise training. In contrast to the skeletal muscle, it is likely
that the low-intensity training does not change the metabolic
state in myocardium of small mammals that sustain high
oxidative metabolism (23, 39).
The expressions of GLUT4 and MCT1 were not affected by
the induction of ischemia and transient MI in both AW and PW
of the LV. This unchanged observation of GLUT4 is similar to
a previous result in failing rat hearts, although GLUT1 protein
levels were increased in the myocardium (31, 50). Thus it is
possible that the increased GLUT1 protein may enhance glu-
cose utilization in the failing heart. Muscle glucose transport
activity has been shown to be primarily related to the number
of facilitative glucose transporters present in the sarcolemmal
membrane (36). Furthermore, the translocation of GLUT4 and
GLUT1 to the sarcolemma can be activated by ischemia or
increased work (62). In the present study, total GLUT4 protein
Fig. 4. Representative Western blots showing amounts of monocarboxylate
transporter 1 (MCT1; A) and GLUT4 (B) of AW and PW in each group. SS,
sedentary sham; ES, exercise sham; SMI, sedentary MI; EMI, exercise MI.
Fig. 3. 3-hydroxyacyl-CoA dehydrogenase (HAD) activities in AW (A) and
PW (B) of the left ventricle. Values are means SE. **P 0.01 vs.
corresponding sham-operated group.
#
P 0.05;
##
P 0.01, AW vs. PW.
846 EXERCISE EFFECT ON MHC AND MCT AFTER MI
J Appl Physiol VOL 97 SEPTEMBER 2004 www.jap.org
o
n

A
p
r
i
l

3
0
,

2
0
1
4
D
o
w
n
l
o
a
d
e
d

f
r
o
m

contents of whole homogenated cardiac muscle were mea-
sured; however, the precise glucose transport activity in the
sarcolemma membrane could not be substantiated.
The data from the present study showed no shift of relative
protein expression in MCT1 in post-MI rats. This observation
is in contrast to a previous study by Johannsson et al. (31), who
reported a 259% increase. We expected that MCT1 would be
upregulated in rat myocardium with MI because failing hearts
have been shown to switch their metabolic preference from
mainly fatty acids to carbohydrates (1, 31, 52). One possible
explanation for the discrepancy in results is the difference in
occlusion and recovery protocols between the studies. For
example, our study reperfused the rats after 30 min of occlu-
sion of the left coronary artery, and after 11 wk they were
killed. On the other hand, Johannsson et al. (31) continued to
ligate the left coronary artery throughout the experiment for 6
wk, which resulted in congestive heart failure (CHF) with
larger cardiac hypertrophy. Therefore, the MCT1 expression of
the survived myocardium in the previous study (31) may
suggest that a greater amount of MCT1 protein would be
expressed to uptake and deliver lactate, thereby compensating
the ischemic region in the heart. Additionally, it might be
plausible to suppose that cardiac MCT1 expression would be
upregulated by chronic stimulation induced by exercise train-
ing and/or CHF. Baker et al. (3) demonstrated increased
cardiac MCT1 with increased duration of moderate exercise. A
recent study (16) has shown a 270% increase in MCT1 protein
expression in CHF rats induced by 8 wk of volume overload
compared with sham-operated rats. In addition, Cuff et al. (13)
have demonstrated that expression of the butyrate transporter,
MCT1, is subject to upregulation by butyrate in colonic epi-
thelial cells and that increased expression of MCT1 mRNA and
protein with butyrate treatment is both dose and time depen-
dent. Moreover, butyrate also stabilized MCT1 mRNA in
colonic epithelial cells (13). Therefore, we suspect that tran-
sient ischemia in the present study, resulting in less of an
increase in heart weight compared with the previous studies
(16, 31), did not induce continuous stimulation enough to cause
a large amount of MCT1 expression. The precise mechanisms
to upregulate the cardiac MCT1 transcription and protein
expression are unclear, however, it has been demonstrated that
the human MCT1 5-anking region contains potential binding
sites for a variety of transcription factors, including activator
protein-1 (AP-1) and nuclear factor-B (NF-B), which are a
well described cellular reaction to oxidative stress (14, 53). The
transcriptional induction mediated by NF-B is transient be-
Fig. 5. MCT1 protein expression in AW (A) and PW of the LV. Values are
means SE. OD, optical density. P 0.05 vs. corresponding sedentary
group.
#
P 0.05, AW vs. PW.
Fig. 6. GLUT4 protein expression in AW (A) and PW (B) of the left ventricle.
Values are means SE. **P 0.01 vs. corresponding sham-operated group.
P 0.05; P 0.01 vs. corresponding sedentary group.
#
P 0.05, AW
vs. PW.
Fig. 7. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis for myosin
heavy chain (MHC)- and MHC- of AW and PW in each group.
847 EXERCISE EFFECT ON MHC AND MCT AFTER MI
J Appl Physiol VOL 97 SEPTEMBER 2004 www.jap.org
o
n

A
p
r
i
l

3
0
,

2
0
1
4
D
o
w
n
l
o
a
d
e
d

f
r
o
m

cause of a rapid downregulation of NF-B DNA-binding
activity by inhibitor (58). In rat pheochromocytoma cells,
binding to AP-1 element remain elevated during prolonged
exposure to hypoxia (24 h) (45). The time course of both
MCT1 gene transcription level and stability of transcript re-
main to be elucidated.
In contrast to the workload on myocardium in post-MI
rats in the present study, a considerable low-intensity
chronic exercise increased relative expression of MCT1
protein in normal myocardium. In support of this, Bonen (5)
suggested the possibility that moderate exercise training
also increases MCT1 in the heart. Furthermore, for the rst
time, we have demonstrated that exercise training increased
the MCT1 expression in the noninfarcted region of the
myocardium in the rats with MI, although the details of
MCT1 localization in cell domains were unknown. This
nding suggests that mild-intensity exercise training, which
might be less harmful in MI rats, enhances the potential
capacity to uptake lactate and oxidize it as an energy
substrate in cardiac muscle of MI rats. As mentioned above,
AP-1 and NF-B are activated by oxidative stress (53),
which could be induced by exercise training (54). By these
effects, chronic exercise training could therefore be thought
to increase the amount of MCT1 in rat myocardium.
It is important to mention that exercise training did not
enhance the MCT1 expression in the AW in MI rats in which
impaired oxidative enzyme activities were observed. Previous
studies have reported that MCT1 facilitates lactate uptake and
oxidation in cells with high mitochondrial densities (10, 11, 15,
37). The AW with low mitochondrial density in MI rats did not
have sufcient capacity to oxidize lactate and therefore did not
support the benet of an increased expression of MCT1 pro-
tein. In contrast, the expression of MCT1 in the PW maintained
with normal mitochondrial density of rat myocardium was
signicantly higher than that in the AW in EMI group. There-
fore, it is plausible that cardiac MCT1 responds to exercise
training in part as CS and HAD to the extent that some of the
change is mitochondrial and in part like GLUT4 because it is
sarcolemmal. Cell domains of the MCT1 respond to exercise
training in the myocardium should be elucidated by dissecting
Fig. 8. MHC- and MHC- protein expressions in AW
(A) and PW (B) of the left ventricle. Values are means
SE. **P 0.01 vs. corresponding sham-operated group.
P 0.01 vs. corresponding sedentary group.
#
P
0.05;
##
P 0.01, AW vs. PW.
Fig. 9. MHC- protein expression in anterior wall-to-posterior wall ratio of
the left ventricle. Values are means SE. Sed, sedentary; Ex, exercise.
848 EXERCISE EFFECT ON MHC AND MCT AFTER MI
J Appl Physiol VOL 97 SEPTEMBER 2004 www.jap.org
o
n

A
p
r
i
l

3
0
,

2
0
1
4
D
o
w
n
l
o
a
d
e
d

f
r
o
m

the components of MCT1 localized in mitochondria and sar-
colemma (10).
Although a recent series of studies has investigated the
mechanisms in upregulation of GLUT4 gene expression in
skeletal muscles by exercise (20, 36, 43), increase in the
expression of GLUT4 protein has not been observed in cardiac
muscle (22, 23). Hall et al. (22) have shown that exercise
training signicantly increased GLUT4 mRNA levels, but did
not alter GLUT4 protein levels of myocardium in male Fischer
344 rats at 7 mo of age, suggesting either a decreased transla-
tional efciency or an increase in the rate of protein degrada-
tion. In the present study, the GLUT4 gene translational ef-
ciency and/or protein degradation rate remain questionable,
although we provided the rst evidence that shows an in-
creased expression of cardiac GLUT4 protein after long-term
exercise training. It is possible that, in the present study, the
increased GLUT4 protein in trained muscle would be localized
in plasma membranes, transverse tubules, and intercalated
disks, which were enriched in our membrane preparation (47,
48), and acted to facilitate continuous glucose utilization to
meet the substrate demand.
We have further demonstrated an increased shift in relative
amount of MHC- in both AW and PW after MI. Under a
stress condition such as pressure overload, the rat hearts
primarily expressed MHC- isoform (24, 29, 38, 46). Myocar-
dial bers that contain relatively more MHC- than MHC-
isoform produce efciently normal tension at a lower oxygen
cost (27, 30). It was likely that a shift to MHC- isoform
expression reected a compensative adaptation of myocardial
metabolism at a lower energy cost to a required oxygen
demand in cardiac dysfunction.
We assessed whether mild-intensity exercise training would
increase expressions of MCT1, GLUT4, and MHC- in the
myocardium of MI rats to improve the cardiac contractile
function. Exercise training enhanced the relative expression of
MHC- isoform in the AW and PW of both sham and MI rats.
A previous investigation also reported that swimming training
enhanced the expression of MHC- in both normotensive and
spontaneously hypertensive rat hearts (51). In addition, several
studies have demonstrated that both running exercise and
swimming exercise attenuated the relative expression of
MHC- in the noninfarcted myocardium in rat with MI (42, 46,
63). Furthermore, previous studies have shown that several
factors, such as sympathetic nervous activity, intracellular
cAMP, and thyroid hormone, could induce an increased ex-
pression of MHC- during and/or after exercise training,
indicating an enhanced shortening velocity of muscle bers (2,
19, 21, 29, 61). However, the mechanisms of the difference in
the expression of MHC isoforms in the response to physiolog-
ical (trained heart) and pathological (post-MI heart) stimuli
remain to be unknown. A previous study demonstrated that

1
-adrenergic receptor (
1
-AR) mRNA concentration in the
LV was increased in both trained rats and spontaneously
hypertensive rats, but in the spontaneously hypertensive rats
the
1
-AR kinase mRNA concentration was also increased,
suggesting an impairment in
1
-AR signal transduction system
(28). Activation of the
1
-AR signal transduction system has
been shown to increase intracellular cAMP concentration,
which would result in an increased expression of MHC- (18,
40). Therefore, it is possible that a difference in an activity of

1
-adrenergic system is one of the causal factors for the
difference in MHC- expression between the trained and
post-MI heart. As a physiological effect of exercise training,
this increased contractile velocity would result in the rever-
sal of the chronotropic incompetence previously observed in
MI rats (2, 42).
Our results provide the rst evidence that the low-intensity
running exercise can enhance the expression of MHC- in the
surviving myocardium of both infarcted and noninfarcted re-
gions in post-MI rats. However, the ratio of the MHC isoforms
shift to MHC- in the PW after exercise training was larger
than that in the AW in MI rats (Figs. 8 and 9). Takashi and
Ashraf (59) demonstrated that, after 30 min of left coronary
artery occulusion and 120 min of reperfusion, in the rat LV
36.3% of the cells remained normal, 26.6% were necrotic, and
25.0% were reversibly injured. In the present study, a MHC-
-to-MHC- isoform shift was imposed on the surviving
myocardium to a greater extent in the AW of the LV where
oxidative enzyme activities were impaired and simultaneously
without changes in the expression of GLUT4 and MCT1. The
observation of a greater shift in MHC- in the surviving
myocardium of the AW, which may result in an improvement
of myocardial work efciency, could be an adapted response to
an augmented delivery of oxygen (24). This interpretation is at
least partly supported by the fact that there was a greater
expression of MHC- in the AW than in the PW in MI rats
(Fig. 9). Particularly in the EMI group, it is likely that the
cardiac muscle in the PW compensates as a whole contractile
machine for the dysfunction of the AW contraction in MI rats
by expressing a greater amount of MHC- isoform compared
with the AW, which would be supported by the increased
expressions of GLUT4 and MCT1. With the ndings taken
together, we concluded that mild-intensity chronic exercise
training increased the expression of MHC- isoform based on
the increased expression of GLUT4 and MCT1 in the PW,
improving the LV function.
It is plausible that the relationship between the exercise-
induced MCT1 expression and MHC isoform shift in the
cardiac muscle is somewhat different from that in the skeletal
muscle. In skeletal muscle, increases in the MCT1 after endur-
ance training or electrical stimulation were accompanied with
a ber-type shift to a more oxidative type, which has lower
ATPase activity (7, 8, 15). On the other hand, our results have
shown that the unaltered expression of MCT1 by exercise
training in the AW in MI rats was not in parallel with the
alteration of MHC isoform expression. This observation may
be due to high oxidative capacity of the cardiac muscle whether
or not it has relatively more of the faster ATPase MHC-
isoform. This view is supported by the fact that the exercise
training enhanced the MHC- expression but did not change
the oxidative capacity in the sham-operated group. Further
research is needed to dene the mechanisms of the MCT
expression and cell domains occupied by MCT1 and other
transport proteins in both cardiac and skeletal muscles.
In summary, surgically induced MI impaired oxidative en-
zyme activities in the AW but not in the PW of the LV in rats.
No differences in the expression of MCT1 were found in either
tissues of AW and PW after MI, whereas exercise training
signicantly increased the MCT1 expression in all conditions,
except AW in the MI rats. Similarly, exercise training resulted
in an increased expression of glucose transporter GLUT4
protein in the AW in the Sham rats and in the PW in the MI
849 EXERCISE EFFECT ON MHC AND MCT AFTER MI
J Appl Physiol VOL 97 SEPTEMBER 2004 www.jap.org
o
n

A
p
r
i
l

3
0
,

2
0
1
4
D
o
w
n
l
o
a
d
e
d

f
r
o
m

rats. The relative amount of MHC- was signicantly in-
creased in the AW and PW in MI rats compared with sham
control. However, exercise training resulted in a signicant
increase of MHC- expression in both AW and PW in both
sham and MI rats (P 0.01). The ratio of the MHC isoforms
shift to MHC- in the PW after exercise training was larger
than that in the AW in MI rats. Stroke volume and cardiac
output increased after exercise training. These ndings suggest
that mild-intensity chronic exercise training increased the ex-
pression of MHC- isoform on the basis of the increased
expression of GLUT4 and MCT1 in the PW, improving the LV
function. Mild exercise training enhanced the potential for
glycolytic metabolism and ATPase activity of myocardium
even in the MI rats, ensuring a benecial role in the remodeling
process of a failing heart.
ACKNOWLEDGMENTS
Authors are very grateful to Dr. Hideo Hatta, Department of Life Science,
University of Tokyo (Tokyo, Japan) for helpful comments and donation of the
MCT1 antibody. We also thank Aaron M. Saikin for assistance in the
preparation of the manuscript.
GRANTS
This research was supported in part by Grant-in-Aid for Scientic Research
10680514 from the Ministry of Education, Science, Sports and Culture of
Japan and by Fund for Experimental Space Utilization Grant U-37.
REFERENCES
1. Allard MF and Lopaschuk GD. Ischemia and reperfusion injury in the
hypertrophied heart. In: Myocardial Ischemia: Mechanisms, Reperfusion,
Protection, edited by Karmazyn M. Basel: Birkhauser, 1996, p. 423441.
2. Alpert NR and Mulieri LA. The response of the heart to stress: a
biological view of myocardial adaptation and failure. J Cardiovasc Phar-
macol 10, Suppl 6: S29S36, 1987.
3. Baker SK, McCullagh KJA, and Bonen A. Training intensity-dependent
and tissue-specic increases in lactate uptake and MCT-1 in heart and
muscle. J Appl Physiol 84: 987994, 1998.
4. Bass A, Brdiczka D, Eyer P, Hofer S, and Pette D. Metabolic differ-
entiation of distinct muscle types at the level of enzymatic organization.
Eur J Biochem 10: 198206, 1969.
5. Bonen A. Lactate transporters (MCT proteins) in heart and skeletal
muscles. Med Sci Sports Exerc 32: 778789, 2000.
6. Bonen A, Miskovic D, Tonouchi M, Lemieux K, Wilson MC, Marette
A, and Halestrap AP. Abundance and subcellular distribution of MCT1
and MCT4 in heart and fast-twitch skeletal muscles. Am J Physiol
Endocrinol Metab 278: E1067E1077, 2000.
7. Bonen A, Tonouchi M, Miskovic D, Heddle C, Heikkila JJ, and
Halestrap AP. Isoform-specic regulation of the lactate transporters
MCT1 and MCT4 by contractile activity. Am J Physiol Endocrinol Metab
279: E1131E1138, 2000.
8. Bottinelli R, Canepari M, Reggiani C, and Stienen GJM. Myobrillar
ATPase activity during isometric contraction and isomyosin composition
in rat single skinned muscle bres. J Physiol 481: 663675, 1994.
9. Brooks GA. Intra- and extra-cellular lactate shuttles. Med Sci Sports
Exerc 32: 790799, 2000.
10. Brooks GA, Brown MA, Butz CE, Sicurello JP, and Dubouchaud H.
Cardiac and skeltal muscle mitochondria have a monocarboxylate trans-
porter MCT1. J Appl Physiol 87: 17131718, 1999.
11. Brooks GA, Dubouchaud H, Brown MA, Sicurello JP, and Butz CE.
Role of mitochondrial lactate dehydrogenase and lactate oxidation in the
intracellular lactate shuttle. Proc Natl Acad Sci USA 96: 11291134, 1999.
12. Chen L, Nohara R, Hirai T, Li X, Kataoka K, Hosokawa R, Masuda
D, Fujita M, Taguchi S, and Sasayama S. Effects of exercise training on
myocardial fatty acid metabolism in rats with depressed cardiac function
induced by transient ischemia. Jpn Circ J 65: 550555, 2001.
13. Cuff MA, Lambert DW, and Shirazi-Beechey SP. Substrate-induced
regulation of the human colonic monocarboxylate transporter, MCT1.
J Physiol 539: 361371, 2002.
14. Cuff MA and Shirazi-Beechey SP. The human monocarboxylate trans-
porter, MCT1: genomic organization and promoter analysis. Biochem
Biophys Res Commun 539: 361371, 2002.
15. Dubouchaud H, Buttereld GE, Wolfel EE, Bergman BC, and Brooks
GA. Endurance training, expression, and physiology of LDH, MCT1, and
MCT4 in human skeletal muscle. Am J Physiol Endocrinol Metab 278:
E571E579, 2000.
16. Evans RK, Schwartz DD, and Gladden LB. Effect of myocardial
volume overload and heart failure on lactate transport into isolated cardiac
myocytes. J Appl Physiol 94: 11691176, 2003.
17. Fregosi RF and Dempsey JA. Arterial blood acid-base regulation during
exercise in rats. J Appl Physiol 57: 396402, 1984.
18. Garcia CK, Goldstein JL, Pathak RK, Anderson GW, and Brown MS.
Molecular characterization of a membrane transporter for lactate, pyru-
vate, and other monocarboxylates: implications for the Cori cycle. Cell 76:
865873, 1994.
19. Goldfarb AH, Bruno JF, and Buckenmeyer PJ. Intensity and duration
effects of exercise on heart cAMP, phosphorylase, and glycogen. J Appl
Physiol 60: 12681273, 1986.
20. Goodyear LJ. AMP-activated protein kinase: a critical signalimg inter-
mediary for exercise-stimulated glucose transport? Exerc Sport Sci Rev 28:
113116, 2000.
21. Gupta MP, Gupta M, Dizon E, and Zak R. Sympathetic control of
cardiac myosin heavy chain gene expression. Mol Cell Biochem 157:
117124, 1996.
22. Hall JL, Mazzeo RS, Podolin DA, Cartee GD, and Stanley WC.
Exercise training does not compensate for age-related decrease in myo-
cardial GLUT-4 content. J Appl Physiol 76: 328332, 1994.
23. Hall JL, Sexton WL, and Stanley WC. Exercise training attenuates the
reduction in myocardial GLUT-4 in diabetic rats. J Appl Physiol 78:
7681, 1995.
24. Hashimoto T, Yamasaki S, and Taguchi S. Alterations in the expression
of myosin heavy chain isoforms in hypoxia-induced hypertrophied ven-
tricles in rats. Comp Biochem Physiol B Biochem Mol Biol 136: 139145,
2003.
25. Himori N and Matsuura A. A simple technique for occlusion and
reperfusion of coronary artery in conscious rats. Am J Physiol Heart Circ
Physiol 256: H1719H1725, 1989.
26. Hirai T, Nohara R, Ogoh S, Chen LG, Kataoka K, Li XH, Fujita M,
Matsumori A, Taguchi S, and Sasayama S. Serial evaluation of fatty
acid metabolism in rats with myocardial infarction by pinhole SPECT.
J Nucl Cardiol 8: 472481, 2001.
27. Holubarsch CH, Goulette RP, Litten RZ, Martin BJ, Mulieri LA, and
Alpert NR. The economy force development, myosin isozyme pattern and
myobrillar ATPase activity in normal and hyperthyroid rat myocardium.
Circ Res 56: 7886, 1985.
28. Iemitsu M, Miyauchi T, Maeda S, Sakai S, Kobayashi T, Fujii N,
Miyazaki H, Matsuda M, and Yamaguchi I. Physiological and patho-
logical cardiac hypertrophy induce different molecular phenotypes in the
rat. Am J Physiol Regul Integr Comp Physiol 281: R2029R2036, 2001.
29. Izumo S, Lompre AM, Matsuoka R, Kore G, Schwartz K, Nadal-
Ginard B, and Mahdavi V. Myosin heavy chain messenger RNA and
protein isoform transitions during cardiac hypertrophy. Interaction be-
tween hemodynamic and thyroid hormone-induced signals. J Clin Invest
79: 970977, 1987.
30. Jacob R, Kissling G, Rupp H, and Vogt M. Functional signicance of
contractile proteins in cardiac hypertrophy and failure. J Cardiovasc
Pharmacol 10, Suppl 6: S2S12, 1987.
31. Johannsson E, Lunde PK, Heddle C, Sjaastad I, Thomas MJ, Berg-
ersen L, Halestrap AP, Blackstad TW, Ottersen OP, and Sejersted
OM. Upregulation of the cardiac monocarboxylate transporter MCT1 in a
rat model of congestive heart failure. Circulation 104: 729734, 2001.
32. Juel C and Halestrap AP. Lactate transport in skeletal musclerole and
regulation of the monocarboxylate transporter. J Physiol 517: 633642,
1999.
33. Kawamoto M, Tamaki N, Yonekura Y, Magata Y, Tadamura E,
Nohara R, Matsumori A, Sasayama S, and Konishi J. Signicance of
myocardial uptake of iodine 123-labeled -methyl iodophenyl pentade-
canoic acid: comparison with kinetics of carbon 11-labeled palmitate in
positron emission tomography. J Nucl Cardiol 1: 522528, 1994.
34. Kitaura T, Tsunekawa N, and Hatta H. Decreased monocarboxylate
transporter 1 in rat soleus and EDL muscles exposed to clenbuterol. J Appl
Physiol 91: 8590, 2001.
850 EXERCISE EFFECT ON MHC AND MCT AFTER MI
J Appl Physiol VOL 97 SEPTEMBER 2004 www.jap.org
o
n

A
p
r
i
l

3
0
,

2
0
1
4
D
o
w
n
l
o
a
d
e
d

f
r
o
m

35. Laemmli UK. Cleavage of structural proteins during the assembly of the
head of bacteriophage T4. Nature 227: 680685, 1970.
36. MacLean PS, Zheng D, and Dohm L. Muscle glucose transporter
(GLUT4) gene expression during exercise. Exerc Sport Sci Rev 28:
148152, 2000.
37. McCullagh KJA, Poole RC, Halestrap AP, OBrien M, and Bonen A.
Role of the lactate transporter (MCT1) in skeletal muscles. Am J Physiol
Endocrinol Metab 271: E143E150, 1996.
38. Mercadier JJ, Lompre M, Wisnewsky C, Samuel JL, Bercovici J,
Swynghedauw B, and Schwartz K. Myosin isoenzymic changes in
several models of rat cardiac hypertrophy. Circ Res 49: 525532, 1981.
39. Moore RL and Palmer BM. Exercise training and cellular adaptations of
normal and diseased hearts. Exerc Sport Sci Rev 27: 285315, 1999.
40. Morgan HE and Baker KM. Cardiac hypertrophy. Mechanical, neural,
and endocrine dependence. Circulation 83: 1325, 1991.
41. Musch TI, Moore RL, Leathers DJ, Bruno A, and Zelis R. Endurance
training in rats with chronic heart failure induced by myocardial infarction.
Circulation 74: 431441, 1986.
42. Musch TI, Moore RL, Smaldone PG, Riedy M, and Zelis R. Cardiac
adaptations to endurance training in rats with a chronic myocardial
infarction. J Appl Physiol 66: 712719, 1989.
43. Musi M and Goodyear LJ. AMP-activated protein kinase and muscle
glucose uptake. Acta Physiol Scand 178: 337345, 2003.
44. Neubauer S, Horn M, Naumann A, Tian R, Hu K, Laser M, Friedrich
J, Gaudron P, Schnackerz K, Ingwall JS, and Ertl G. Impairment of
energy metabolism in intact residual myocardium of rat hearts with
chronic myocardial infarction. J Clin Invest 95: 10921100, 1995.
45. Norris ML and Millhorn DE. Hypoxia-induced protein binding to
O2-responsive sequences on the tyrosine hydroxylase gene. J Biol Chem
270: 2377423779, 1995.
46. Orenstein TL, Parker TG, Butany JW, Goodman JK, Dawood F, Wen
WH, Wee L, Martino T, McLaughlin PR, and Liu PP. Favorable left
ventricular remodeling following large myocardial infarction by exercise
training. J Clin Invest 96: 858866, 1995.
47. Ploug T, Galbo H, Ohkuwa T, Tranum-Jensen J, and Vinten J.
Kinetics of glucose transport in rat skeletal muscle membrane vesicles:
effects of insulin and contractions. Am J Physiol Endocrinol Metab 262:
E700E711, 1992.
48. Ploug T, Wojtaszewski J, Kristiansen S, Hespel P, Galbo H, and
Richter EA. Glucose transport and transporters in muscle giant vesicles:
differential effects of insulin and contractions. Am J Physiol Endocrinol
Metab 264: E270E278, 1993.
49. Reiser PJ and Kline WO. Electrophoretic separation and quantitation of
cardiac myosin heavy chain isoforms in eight mammalian species. Am J
Physiol Heart Circ Physiol 274: H1048H1053, 1998.
50. Rosenblatt-Velin N, Montessuit C, Papageorgiou I, Terrand J, and
Lerch R. Postinfarction heart failure in rats is associated with upregula-
tion of GLUT-1 and downregulation of genes of fatty acid metabolism.
Cardiovasc Res 52: 407416, 2001.
51. Rupp H. Differential effect of physical exercise routines on ventricular
myosin and peripheral catecholamine stores in normotensive and sponta-
neously hypertensive rats. Circ Res 65: 370377, 1989.
52. Sambandam N, Lopaschuk GD, Brownsey RW, and Allard MF.
Energy metabolism in the hypertrophied heart. Heart Fail Rev 7: 161173,
2002.
53. Sen CK and Packer L. Antioxidant and redox regulation of gene
transcription. FASEB J 10: 709720, 1996.
54. Sen CK and Packer L. Thiol homeostasis and supplements in physical
exercise. Am J Clin Nutr 72, Suppl: 653S669S, 2000.
55. Sethi R, Dhalla KS, Beamish RE, and Dhalla NS. Differential changes
in left and right ventricular adenylyl cyclase activities in congestive heart
failure. Am J Physiol Heart Circ Physiol 272: H884H893, 1997.
56. Srere PA. The citrate enzymes: their structures, mechanisms, and biolog-
ical functions. Curr Top Cell Regul 5: 229283, 1972.
57. Sugiura S and Yamashita H. Functional characterization of cardiac
myosin isoforms. Jpn J Physiol 48: 173179, 1998.
58. Sun SC, Ganchi PA, Ballard DW, and Greene WC. NF-B controls
expression of inhibitor IB: evidence for an inducible autoregulatory
pathway. Science 259: 19121915, 1993.
59. Takashi E and Ashraf M. Pathologic assessment of myocardial cell
necrosis and apoptosis after ischemia and reperfusion with molecular and
morphological markers. J Mol Cell Cardiol 32: 209224, 2000.
60. Talmadge RJ and Roy RR. Electrophoretic separation of rat skeletal
muscle myosin heavy-chain isoforms. J Appl Physiol 75: 23372340,
1993.
61. Wirth A, Holm G, Lindstedt G, Lundberg PA, and Bjorntorp P.
Thyroid hormones and lipolysis in physically trained rats. Metabolism 30:
237241, 1981.
62. Young LH, Russell RR III, Yin R, Caplan MJ, Ren J, Bergeron R,
Shulman GI, and Sinusas AJ. Regulation of myocardial glucose uptake
and transport during ischemia and energetic stress. Am J Cardiol 83:
25H30H, 1999.
63. Zhang XQ, Ng YC, Musch TI, Moore RL, Zelis R, and Cheung JY.
Sprint training attenuates myocyte hypertrophy and improves Ca
2
ho-
meostasis in postinfarction myocytes. J Appl Physiol 84: 544552, 1998.
851 EXERCISE EFFECT ON MHC AND MCT AFTER MI
J Appl Physiol VOL 97 SEPTEMBER 2004 www.jap.org
o
n

A
p
r
i
l

3
0
,

2
0
1
4
D
o
w
n
l
o
a
d
e
d

f
r
o
m