Skeletal Muscle Deoxygenation Abnormalities

in Early Post-Myocardial Infarction

CLINICAL SCIENCES

SHUN TAKAGI1, NORIO MURASE1, RYOTARO KIME1, MASATSUGU NIWAYAMA2, TAKUYA OSADA1,
and TOSHIHITO KATSUMURA1
1
Department of Sports Medicine for Health Promotion, Tokyo Medical University, Tokyo, JAPAN; and 2Department of
Electrical and Electronic Engineering, Faculty of Engineering, Shizuoka University, Shizuoka, JAPAN

ABSTRACT
TAKAGI, S., N. MURASE, R. KIME, M. NIWAYAMA, T. OSADA, and T. KATSUMURA. Skeletal Muscle Deoxygenation Ab-
normalities in Early Post-Myocardial Infarction. Med. Sci. Sports Exerc., Vol. 46, No. 11, pp. 2062–2069, 2014. Purpose: Reduced peak
aerobic capacity in chronic heart failure can be partly explained by impaired peripheral factors. However, skeletal muscle deoxygenation
responses during exercise and their relation to peak aerobic capacity have not been fully established in early post-myocardial infarction
(MI) patients. Methods: Patients early post-MI (age, 61 T 9 yr; n = 16; 21 T 8 d after the first MI) and age-, height-, and weight-matched
control participants (age, 61 T 9 yr; n = 18) performed a ramp cycling exercise until exhaustion. Near-infrared spectroscopy at the belly of
the vastus lateralis muscle in the left leg was recorded continuously for measurement of skeletal muscle deoxygenation responses during
exercise. Results: Peak oxygen uptake (18.4 T 3.5 vs 28.2 T 10.7 mLIkgj1Iminj1, P G 0.01) was significantly lower in MI. Change in
muscle oxygen saturation from rest to peak exercise ($SmO2) was significantly greater in MI than that in controls (2.5% T 5.6% vs
j7.4% T 3.4%, P G 0.01). Relative change in deoxygenated hemoglobin/myoglobin concentration from rest to peak exercise ($deoxy-
Hb/Mb) was significantly lower in MI than that in controls (0.1 T 3.6 vs 8.7 T 6.4 KM, P G 0.01). In contrast, change in total hemoglobin/
myoglobin, which is an indicator of blood volume, was not significantly different between groups. Peak oxygen uptake was negatively
correlated with $SmO2 (r = j0.53, P G 0.05) and positively associated with $deoxy-Hb/Mb at peak exercise (r = 0.65, P G 0.01) in MI.
Conclusions: Skeletal muscle deoxygenation abnormalities were observed during dynamic cycling exercise in early post-MI patients.
These abnormalities were related to impaired peak aerobic capacity in early post-MI patients. Key Words: NEAR INFRARED
SPECTROSCOPY, OXYGEN TRANSPORT, CYCLING EXERCISE, HEART DISEASE, MICROCIRCULATION

H
eart disease patients have been characterized by re-
ports of reduced peak aerobic capacity (4,9,40). Many
previous studies demonstrated that reduced peak aer-
obic capacity in patients with chronic heart failure (CHF) can
be explained not only by reduced output of the heart but also
by reduced skeletal muscle blood flow (31,32), reduced aer-
obic enzyme activity, and an increased percentage of fast
twitch-type fibers in the skeletal muscle (9). However,early
after myocardial infarction (MI), peripheral factors and their
relation to reduced peak aerobic capacity have not been fully
established.
The near-infrared spectroscopy (NIRS) technique provides
oxygen balance between supply and use in the arterioles,
capillaries, and venules of localized exercising muscle non-
invasively during dynamic exercise (14). Previous studies eval-
uated the peripheral circulatory and metabolic impairment
Address for correspondence: Shun Takagi, Ph.D., Department of Sports
Medicine for Health Promotion, Tokyo Medical University, 6-1-1 Shinjuku,
Shinjuku-ku, Tokyo 160-8402, Japan; E-mail: stakagi@tokyo-med.ac.jp.
Submitted for publication July 2013.
Accepted for publication March 2014.
0195-9131/14/4611-2062/0
MEDICINE & SCIENCE IN SPORTS & EXERCISEÒ
Copyright Ó 2014 by the American College of Sports Medicine
DOI: 10.1249/MSS.0000000000000334
in CHF (4,40), peripheral arterial disease (2,22), and mito-
chondrial myopathy (13,29) by using the NIRS technique. In
addition, skeletal muscle deoxygenation measured by NIRS
during dynamic exercise was associated with peak aerobic
capacity (7,29,40). However, there are no studies of muscle
deoxygenation responses during exercise and their relation to
peak aerobic capacity in early post-MI. Assessing skeletal
muscle deoxygenation responses can be helpful to clarify
peripheral impairment and its relation to reduced peak aerobic
capacity in MI patients. Hence, the purpose of this study was
to investigate skeletal muscle deoxygenation responses dur-
ing cycling exercise and their relation to peak aerobic ca-
pacity in early post-MI patients.
METHODS
Subjects. Sixteen patients soon after MI, whose physical
and clinical characteristics are shown in Table 1, participated
in the study. The first MI patients enrolled 21 T 9 d (ranged
12–45 d) after onset of heart attack. Eight patients had an-
terior MI, seven patients had inferior MI, and one patient
had lateral MI. All MI patients had received percutaneous
coronary intervention before the present study. Eleven pa-
tients had one-vessel disease, three patients had two-vessel
disease, and two patients had three-vessel disease before per-
cutaneous coronary intervention. Patients with peripheral

2062

Copyright © 2014 by the American College of Sports Medicine. Unauthorized reproduction of this article is prohibited.
TABLE 1. Physical and clinical characteristics and medication profiles.
MI (n = 16)
Age (yr) 61 T 9
Height (cm) 165.5 T 8.1
Weight (kg) 67.5 T 13.0
Men/women 13/3
Hemoglobin (gIdLj1) 13.4 T 1.8
Hematocrit (%) 39.8 T 5.2
Peak creatine kinase (IUILj1) 3057 T 1891
Medication (%)
ACE inhibitor 81
Angiotensin II receptor antagonist 25
Beta blockers 75
Calcium channel antagonist 25
Diuretics 31
Diabetes (%) 13
Dyslipidemia (%) 68
Hypertension (%) 63
Values are means T SD.
ACE, angiotensin converting enzyme; NA, not available.
vascular disease, postinfarction angina, critical arrhythmia,
unstable heart failure, or lung disease were excluded. In
patients with MI, the mean left ventricular ejection fraction
(LVEF) was 55% T 8% (ranged from 40% to 68%), as
assessed by echocardiography. During their disease, peak
creatine kinase concentration was 3057 T 1891 (IUILj1) in
MI. We also studied 18 age-, height-, and weight-matched
normal subjects as controls (CON) (Table 1). Before exer-
cise testing (see succeeding section), all MI patients partic-
ipated in approximately five sessions of exercise training as
part of cardiac rehabilitation in the hospital. A session con-
sisted of continuous cycling exercise for 30 min according to
the individual 3 METs. On average, control subjects engaged
in a recreational physical activity, such as walking or cycling,
for 1–2 hIwkj1. The study protocol was approved by an in-
stitutional review committee and was conducted in accor-
dance with the Declaration of Helsinki. All subjects were
informed of the purpose and nature of the study, and a written
informed consent was obtained.
Exercise testing. Subjects exercised on an upright elec-
tromechanical cycling ergometer (Strength Ergo 8; Fukuda-
Denshi, Tokyo, Japan) using a ramp protocol (10 WIminj1
for MI patients after a 3-min warm-up at 10 W, 15 WIminj1,
or 20 WIminj1 for CON after a 3-min warm-up at 15 W or
20 W) until exhaustion. During exercise periods, pedal fre-
quency was maintained at 50 rpm by keeping time with a
metronome. Subjects were monitored by the investigators
and given verbal encouragement when required. All subjects
exercised until they could no longer sustain the required
cadence. A 12-lead ECG (ML-9000 Stress Test System;
Fukuda-Denshi, Tokyo, Japan) was monitored continuously
during the exercise, and HR was derived from the RR in-
terval. The pulmonary oxygen uptake (V̇O2) and carbon
dioxide production (CO2) were assessed breath by breath
with an online metabolic system (AE300S; Minato Medical
Science, Osaka, Japan) to determine V̇O2peak and estimated
lactate threshold (LT) using the V-slope method and cor-
roborated in the profiles of the end-tidal partial pressures
of O2 and CO2, the ventilatory equivalents for V̇O2 and
MUSCLE DEOXYGENATION IN EARLY POST-MI
Copyright © 2014 by the American College of Sports Medicine. Unauthorized reproduction of this article is prohibited.
V̇CO2, and RER (3,39). The $V̇O2/$WR slope during ramp
CON (n = 18) exercise was determined by the linear regression of V̇O2
60 T 10 with work rate (WR) from 4 min after the beginning of the
CLINICAL SCIENCES
165.2 T 8.1
62.9 T 10.3
ramp loading up to the point that represented 80% of the
14/4 total duration of ramp exercise (6). Even though the analysis
13.8 T 1.0 (n = 14) of the sub-LT region of the response would be ideal, this can
41.1 T 3.0 (n = 14)
NA result in the fit being based on only a very small amount
of data and the resulting $V̇O2/$WR slope becomes un-
0
11 stable. The mean response time (MRT) in V̇O2 during ramp
0 exercise was calculated as the time from onset of the ramp
11
0
workload to the point of intersection between the baseline
11 V̇O2 during warm-up and a backward extrapolation of the
55 V̇O2 versus time slope (5). The baseline V̇O2 was defined as
38
the mean of V̇O2 during the last 2 min of warm-up. For some
subjects in MI and CON, workloads 4 min after onset of
ramp loading were higher than workloads at estimated LT.
Therefore, the whole slope of $V̇O2/$WR and the MRT
were calculated using data from eight MI patients and seven
CON subjects. During the rest periods without pedaling,
subjects sat on the bicycle with the left foot on the pedal,
at the lowest position.
Skeletal muscle oxygenation measurements. Relative
changes from rest in oxygenated hemoglobin/myoglobin con-
centration ($oxy-Hb/Mb), deoxygenated hemoglobin/myoglobin
concentration ($deoxy-Hb/Mb), total hemoglobin/myoglobin
concentration ($total-Hb/Mb), and muscle oxygen satura-
tion (SmO2) were continuously monitored at the belly of the
vastus lateralis (VL) muscle in the left leg by near-infrared
spatial resolved spectroscopy (NIRSRS). The measurement
site in the VL was defined as 30% of the length between the
patella and the greater trochanter above the patella. The NIRSRS
values were defined as the values averaged over the last 10 s
at rest, every 20 W, and peak exercise.
NIRSRS system. We used a two-wavelength (770 and
830 nm) light-emitting diode NIRSRS (Astem Co, Japan).
The probe consisted of one light source and two photodiode
detectors, and the optode distances were 20 and 30 mm, as
were used in previous studies for measuring muscle oxy-
genation (34). The NIRSRS technique provides relative changes
in Hb/Mb and absolute value of SmO2. Relative changes
in Hb/Mb were derived from light absorption according
to the modified Beer–Lambert law. The absolute value of
SmO2 was calculated by the relative absorption coefficients
obtained from the slope of light attenuation over a distance
measured at two focal points from the light emission. The
data sampling rate was 1 Hz. A previous study reported that
fat layer thickness affects NIRS data because of light scat-
tering (16). In contrast, Niwayama et al. (24) has recently
reported that the effects of fat layer thickness can be corrected
in relative changes in Hb/Mb or absolute value of SmO2. For
the calculation of relative change in Hb/Mb, acorrection curve
(regarding fat layer thickness and normalized optical path
length for muscles) that was obtained from results of a Monte
Carlo simulation was used. The optical path length for mus-
cle is normalized by the curve when the fat layer thick-
ness is zero. The relation between normalized optical path
Medicine & Science in Sports & Exercised 2063
 length Smuscle and fat layer thickness h can be approximately
expressed as the following equation: Smuscle = exp[j(h/A)2].
The value of constant A for the source–detector separations
CLINICAL SCIENCES

of 30 mm is 8.0. Therefore, the value of Smuscle can be de-

termined only by h previously measured by ultrasound de-
vice. Finally, the corrected concentrations were obtained by
dividing the measured values by Smuscle. For the calculations
of SmO2, a curve regarding the relation between the spatial
slope of light intensity S and absorption coefficient of
the muscle Kam was obtained by Monte Carlo simulation.
The S–Kam curve depends on the fat layer thickness. The
measurements using NIRSRS can be corrected by using the
appropriate S–Kam curve for fat layer thickness. The specifi-
cations of correction for the influence of fat layer thickness
have been fully described (24). In this study, we measured fat
layer thickness at the measurement site in the VL muscles
using an ultrasound device (LogiQ3; GE Yokogawa Medical
Systems, Japan) by placing an ultrasound probe on the same
sites the NIRS probes had been placed on. Then, we used an
NIRS device, which has a built-in fat-correction software (Astem
Co, Japan), and relative changes in Hb/Mb and absolute value
of SmO2 with correction for the influence of fat layer thick-
ness were obtained. Even though an upper limit of fat layer
thickness was designated as 10 mm to correct for the light-
scattering effects in this study, fat layer thickness measure-
ments in MI and CON were 4.75 T 1.23 mm (ranged from FIGURE 1—Change in V̇O2 (A), HR (B), oxygen pulse (C), and RER
2.70 to 8.16 mm) and 4.78 T 2.23 mm (ranged from 2.43 to (D) during ramp cycling exercise expressed as a function of power
output. The closed circles show NIRS signals in MI, and the open circles
8.73 mm), respectively. show NIRS signals in CON. Significant difference between MI and
Statistical analysis. All data are given as means T SD. CON during submaximal exercise (*P G 0.05, **P G 0.01). There was
To compare changes in NIRS variables and cardiorespira- a significant exercise group–power output interaction (#P G 0.05,
##P G 0.01). Significant difference between MI and CON at peak
tory variables during submaximal exercise between groups exercise (†P G 0.05, ††P G 0.01). For the sake of clarity, symbols
over power output, two-way repeated-measures ANOVA indicating a significant difference between power output in both
was used with group and power output as factors. Where groups have been omitted.
appropriate, Bonferroni post hoc test was performed to de-
termine specific significant differences. Because one subject 0.54) or oxygen pulse (P = 0.40). Moreover, no significant
could not exercise at more than 62 W, repeated measures main effect for groups was observed in HR or oxygen pulse.
between groups were limited to rest, 20, 40, and 60 W com- During submaximal exercise, V̇O2 was significantly lower at
pared as a function of power output. Differences in NIRS var- 20, 40, and 60 W in MI. Mean V̇O2 in MI at 20 W
iables at peak exercise, $SmO2 (SmO2 at peak exercise minus corresponded to 85% of mean V̇O2 in CON at 20 W; mean
SmO2 at rest), and cardiorespiratory variables at peak exer- V̇O2 in MI at 40 W corresponded to 85% of mean V̇O2
cise were compared between groups using unpaired t-tests. in CON at 40 W; mean V̇O2 in MI at 60 W corresponded to
Pearson correlation coefficient was used to determine the re- 82% of mean V̇O2 in CON at 60 W. The $V̇O2/$WR
lation between variables in MI. To determine the strength of slope was not significantly different between groups (MI,
the relation between the NIRS signals and peak aerobic ca- 10.2 T 1.0 mLIminj1IWj1; CON, 10.2 T 0.5 mLIminj1IWj1;
pacity, a regression analysis was conducted on data from MI P = 0.99). The MRT in MI is longer than that in CON
and CON. The ANOVA and correlation coefficient were ana- (MI, 77 T 16 s; CON, 50 T 11 s; P G 0.05). No signif-
lyzed by SPSS version 17.0J (SPSS Inc., Chicago, IL). For all icant difference in HR was observed during submaximal
statistical analyses, significance was accepted at P G 0.05. exercise between MI and CON. RER was significantly
higher at 40 W and 60 W in MI during submaximal exercise.
V̇O2peak (MI, 18.4 T 3.5 mLIkgj1Iminj1; CON, 28.2 T
RESULTS 10.7 mLIkgj1Iminj1; P G 0.01) and peak workloads (MI, 94 T
Cardiorespiratory variables. Figure 1 represents the 16 W; CON, 148 T 65 W; P G 0.01) were significantly lower
changes in V̇O2 (A), HR (B), oxygen pulse (C), and RER in MI compared with those in CON. Estimated LT was
(D) as a function of WR. During submaximal exercise, there also significantly lower in MI than that in CON (MI, 11.3 T
were significant group–power output interactions for change 2.5 mLIkgj1Iminj1; CON, 18.2 T 7.9 mLIkgj1Iminj1;
in V̇O2 (P G 0.01) and RER (P G 0.05) but not in HR (P = P G 0.01) but occurred at a similar percentage of V̇O2peak in

2064 Official Journal of the American College of Sports Medicine http://www.acsm-msse.org

Copyright © 2014 by the American College of Sports Medicine. Unauthorized reproduction of this article is prohibited.
both groups (MI, 61.7% T 8.1% V̇O2peak; CON, 64.1% T 9.8%
V̇O2peak; P = 0.45). HRmax was significantly lower in MI
patients compared with that in controls (MI, 133 T 13 beats
per minute; CON, 151 T 29 beats per minute; P G 0.05).
Peak RER was not significantly different between groups
(MI, 1.22 T 0.08; CON, 1.19 T 0.07; P = 0.20). Oxygen
pulse at peak exercise was not significantly different
between MI and CON (MI, 9.0 T 2.2 mL per beat; CON,
10.5 T 3.4 mL per beat; P = 0.14).
Muscle deoxygenation responses. Figure 2 illus-
trates the change in SmO2 (A), $oxy-Hb/Mb (B), $deoxy-
Hb/Mb (C), and $total-Hb/Mb (D) for MI patients and CON
during exercise as a function of power output. During sub-
maximal exercise, there were significant group–power out-
put interactions for change in SmO2 (P G 0.01), $oxy-Hb/Mb
(P G 0.05), and $deoxy-Hb/Mb (P G 0.01), but not in
$total-Hb/Mb (P = 0.896). Moreover, no significant main
effect for groups was observed in $total-Hb/Mb, which is
an indicator of blood volume. For CON, as power output
increased, SmO2 was significantly decreased at 60 W com-
FIGURE 2—Change in SmO2 (A), oxy-Hb/Mb (B), deoxy-Hb/Mb (C),
and total-Hb/Mb (D) in the VL muscle during ramp cycling exercise
expressed as a function of power output. The closed circles show NIRS
signals in MI, and the open circles show NIRS signals in CON. Signif-
icant difference between MI and CON during submaximal exercise
(*P G 0.05, **P G 0.01). There was a significant exercise group–power
output interaction (#P G 0.05, ##P G 0.01). Significant difference between
MI and CON at peak exercise (†P G 0.05, ††P G 0.01). For the sake of
clarity, symbols indicating a significant difference between power output
in both groups have been omitted.
MUSCLE DEOXYGENATION IN EARLY POST-MI
Copyright © 2014 by the American College of Sports Medicine. Unauthorized reproduction of this article is prohibited.
pared with that in rest (P G 0.01). In contrast, SmO2 was not
significantly decreased during exercise in MI, and the SmO2
at 60 W (P G 0.05) was significantly higher in MI than that in
CLINICAL SCIENCES
CON. $oxy-Hb/Mb was significantly higher at 60 W (P G
0.01) in MI than that in CON, even though it was relatively
maintained as power output increased in CON. Whereas
$deoxy-Hb/Mb was enhanced in CON, it was not signifi-
cantly increased during exercise from rest in MI. As a result,
$deoxy-Hb/Mb was significantly lower in MI compared with
that in CON at 40 W (P G 0.05) and 60 W (P G 0.01). At peak
exercise, the SmO2 was significantly greater in MI than that
in CON (P G 0.01) and, consequently, $SmO2 was signifi-
cantly greater in MI (MI, 2.5% T 5.6%; CON, j7.4% T
3.4%; P G 0.01). $oxy-Hb/Mb at peak exercise was signifi-
cantly higher in MI than that in CON (P G 0.01), and $deoxy-
Hb/Mb at peak exercise was significantly lower in MI than
that in CON (P G 0.01). However, no significant difference in
$total-Hb/Mb was observed between groups at peak exercise.
Correlation analysis. In the MI patients, $SmO2 was
significantly negatively correlated to V̇O2peak (r = j0.53,
P G 0.05) and estimated LT (r = j0.52, P G 0.05). In ad-
dition, in MI, there was a significantly positive correla-
tion between $deoxy-Hb/Mb at peak exercise and V̇O2peak
(r = 0.65, P G 0.01) or estimated LT (r = 0.62, P G 0.01). In
the all subjects (MI and CON), there was a significant ex-
ponential relation between $SmO2 and V̇O2peak (R2 = 0.80,
P G 0.01) (Fig. 3A) or estimated LT (R2 = 0.75, P G 0.01)
(Fig. 3B). Similarly, significant relations were observed
between $deoxy-Hb/Mb at peak exercise and V̇O2peak
(R2= 0.56, P G 0.01) (Fig. 3C) or estimated LT (R2 = 0.55,
P G 0.01) (Fig. 3D).
Remarkably, the number of days after onset of MI
was positively correlated with $SmO2 (r = 0.57, P G 0.05)
(Fig. 4A) and negatively associated with $deoxy-Hb/Mb
at peak exercise (r = j0.51, P G 0.05) (Fig. 4B). Further-
more, a greater number of days after onset of MI tended
to be correlated with lower V̇O2peak (r = j0.49, P = 0.05)
(Fig. 4C) and estimated LT (r = j0.43, P = 0.09) (Fig. 4D).
However, the number of days after MI was not significantly
related to resting LVEF (P = 0.22), $oxy-Hb/Mb (P = 0.19),
or $total-Hb/Mb (P = 0.65) at peak exercise.
DISCUSSION
The present study provides two major findings. First, during
incremental exercise, SmO2 did not decrease in MI skeletal
muscles, even though deoxygenation was enhanced in CON as
power output increased. These abnormalities during exercise
were a result of increased oxy-Hb/Mb and a minor increase in
deoxy-Hb/Mb response, even though total-Hb/Mb responses
were similar between groups. Taken together, these abnor-
malities imply that O2 extraction was lower in MI compared
with that in CON in the present study. Because SmO2 re-
sponses were also significantly different at a given absolute
workload, differences in SmO2 responses are not solely ascribed
to differences in maximal workload. Second, deoxygenation
Medicine & Science in Sports & Exercised 2065
 systemic vascular resistance early after mild-to-moderate in-
farction of acute onset (8,10), especially in animal experi-
ments. However, to our knowledge, there have been no
CLINICAL SCIENCES

reports that higher muscle blood flow was observed in MI

patients compared with that in CON. Future studies are
needed to examine muscle oxygen perfusion directly during
exercise in early after-MI patients because O2 extraction is
affected by O2 supply itself (26). Furthermore, O2 extraction
is potentially affected by structural (muscle fiber-type com-
position, capillary bed) and functional (neurohumoral, reflex,
or inflammatory) factors in heart failure patients (25). In
particular, a recent review indicates that nitric oxide bio-
availability plays an important role in matching muscle blood
flow to muscle O2 consumption (25). We should confirm the
detailed mechanisms of the lower O2 extraction in MI patients.
Even though lower muscle O2 extraction was found in
early post-MI patients, V̇O2 was also significantly lower
during submaximal exercise because of slower V̇O2 kinetics
consequent to low muscle O2 supply or muscle oxidative
capacity (20,28) (as will be discussed later). From the re-
sults of these cardiorespiratory variables, we could hypoth-
esize that O2 supply during submaximal exercise may be
impaired in MI patients compared with that in CON, even
though O2 supply was not measured directly in the present
study. However, in early post-MI patients, oxy-Hb/Mb in

FIGURE 3—Relation between muscle deoxygenation responses and

aerobic capacity in MI patients (closed circles) and CON (open circles).
A, $SmO2 and V̇O2peak. B, $SmO2 and estimated LT. C, $deoxy-Hb/
Mb from rest to peak exercise (deoxy-Hb/Mb@peak) and V̇O2peak. D,
deoxy-Hb/Mb@peak and estimated LT.

abnormalities in skeletal muscle were related to peak aerobic

capacity in early post-MI patients.
SmO2, which is measured by NIRS, is an indicator of the
balance between oxygen supply and oxygen use (2,14,34).
The decline of SmO2 during incremental exercise can be
interpreted as higher O2 use than O2 supply, as seen in CON.
Therefore, one potential explanation for the higher SmO2 in
MI is the blunted oxygen use in exercising muscle. Previous
studies demonstrated that citrate synthase activity, which
is an index of mitochondrial capacity, was lower 4 wk after
MI in rat muscles (37,38). Moreover, Thompson et al. (37)
reported that oxidative adenosine triphosphate synthesis
was already impaired 4 wk after MI during exercise in rats.
Furthermore, similar abnormalities of muscle deoxygen-
ation response measured by NIRS were observed in patients
with a metabolic disorder, mitochondrial myopathy (13,29).
There is a possibility that these abnormalities observed in the
present study may have partly been caused by attenuation of
oxygen use in MI, even though oxygen use in the exercising
muscle cannot be directly assessed by the NIRS technique.
Another possible interpretation for the higher SmO2 in MI FIGURE 4—Relation between the number of days after MI and muscle
may be hyperperfusion (overperfusion) due to vasodilation deoxygenation responses or aerobic capacity in MI patients. A, the
number of days after MI and $SmO2. B, the number of days after MI
response. The activation of left ventricular baroreceptors and $deoxy-Hb/Mb (deoxy-Hb/Mb@peak). C, the number of days af-
or chemoreceptors by ischemic myocardium may reduce ter MI and V̇O2peak. D, the number of days after MI and estimated LT.

2066 Official Journal of the American College of Sports Medicine http://www.acsm-msse.org

Copyright © 2014 by the American College of Sports Medicine. Unauthorized reproduction of this article is prohibited.
the exercising muscle was increased during submaximal
exercise as power output increased. Increasing oxy-Hb/Mb
indicates that O2 supply is higher than O2 use in exercising
muscle. Moreover, to our knowledge, there have been no
reports that higher muscle blood flow during exercise was
observed in MI patients, compared with that in control
subjects. Therefore, our findings measured by the NIRS
technique may lead us to speculate that O2 delivery is not a
limiting factor for V̇O2 during submaximal exercise and that
lower O2 extraction, rather than lower O2 delivery, contrib-
utes to lower V̇O2 at a given absolute WR in early post-MI
patients of the present study.
There was some inconsistency of muscle deoxygenation
responses measured by NIRS in heart disease patients among
several previous studies. In CHF patients, muscle deoxygen-
ation was enhanced during submaximal exercise compared
with that in normal subjects (4,21,40). These results from
previous studies can be interpreted as greatly enhanced oxy-
gen extraction to compensate for reduced oxygen delivery. In
contrast, some previous studies indicated that muscle deoxy-
genation levels at peak exercise were similar between CHF
patients and control subjects (4,21,40). However, Mezzani
et al. (21) reported that exercise training significantly enhanced
deoxygenation levels at peak exercise in CHF patients.
Moreover, in heart transplant recipients, deoxygenation
levels at peak exercise were significantly lower than those
in control subjects (17). These data suggest that deoxy-
genation levels at peak exercise may be impaired in heart
disease patients. In the present study of early post-MI, our
findings indicate that oxygen extraction may be lower in
activating muscle during submaximal and peak exercise.
To our knowledge, there have been no studies of muscle
deoxygenation response in early after-MI patients mea-
sured by the NIRS technique, even though the absence of a
decrease in SmO2 during exercise was observed in some
studies of mitochondrial myopathy patients (13,29).
Notably, Sumimoto et al. (33) reported that mixed venous
O2 saturation obtained invasively by a catheter was signifi-
cantly decreased at peak exercise and, consequently, O2
extraction was significantly enhanced in recent MI patients.
These data may be contradictory to our findings measured
by the NIRS technique. Potential reasons for the disparities
among studies may be the difference in the extent of pre-
served heart pump function (the extent of MI). In particular,
the post-MI patients in this study have substantially pre-
served LVEF (a range of 40% to 68%, with a mean of 55% T
8%), compared with MI patients whose LVEF was largely
reduced (a range of 15%–48%, with a mean of 32% T 9%)
in a previous report by Sumimoto et al. (33). Even though
O2 supply to exercising muscle was not measured in the
present and previous studies (33), reduction in O2 supply
to exercising muscle due to reduced pump function of the
heart may potentially cause a compensatory increase in O2
extraction in the exercising muscle. Therefore, the preserved
LVEF may affect the absence of a decrease in SmO2 dur-
ing exercise in the present study. Moreover, methodological
MUSCLE DEOXYGENATION IN EARLY POST-MI
Copyright © 2014 by the American College of Sports Medicine. Unauthorized reproduction of this article is prohibited.
differences could partly explain the disparities among studies.
The mixed venous O2 saturation obtained invasively by a
catheter reflects systemic information, including not only
CLINICAL SCIENCES
exercising muscle, but also inactive regions. In contrast,
NIRS data reflects tissue oxygenation in the arterioles, cap-
illaries, and venules of localized exercising muscle, especially
in the superficial region of the muscle, because the measure-
ment depth of the NIRS technique is approximately equal to
half the distance between the light source and the detector
(14). In addition, a regional difference in deoxygenation re-
sponse measured by NIRS was observed between muscles
and also within a single muscle (34). In fact, Esaki et al. (11)
reported that there is a significant but smaller correlation
between deoxygenation response measured by NIRS in
the distal part of the VL muscle (noninvasive method) and
femoral venous O2 saturation measured by blood sampling
(invasive method). Hence, the muscle deoxygenation abnor-
malities in early post-MI patients may be restricted to
the superficial region of the distal site of the VL muscle.
Furthermore, NIRS yields a very indirect evaluation of oxi-
dative metabolism. NIRS data are influenced not only by O2
use or O2 supply but also by mechanical stress, such as in-
tramuscular pressure. Even though further investigations
are needed to explain the disparities among studies, from our
findings during dynamic cycling exercise measured by NIRS
technique, O2 extraction was not enhanced in around 20 d
after MI patients who did not have severe MI.
The secondary purpose of this study was to determine
whether dynamic O2 imbalance in exercising muscles is re-
lated to reduced peak aerobic capacity in MI. In the present
study, V̇O2peak and estimated LT were negatively correlated
with $SmO2 and were positively related to $deoxy-Hb/Mb.
Remarkably, a greater number of days after the onset of MI
was related to less muscle deoxygenation response during
cycling exercise. A previous study reported that the oxidative
capacity of skeletal muscle, measured by high-resolution res-
pirometry using skeletal muscle biopsy samples, was not sig-
nificantly different between CHF patients and truly sedentary
control subjects (19). These data suggest that reduced aerobic
capacity in the skeletal muscle may be mainly attributed to
deconditioning in heart disease patients. Moreover, in CHF
patients (not including recent MI patients of less than 8 wk),
the volume density of mitochondria was inversely related to
the duration of heart failure, and the change in the volume
density of mitochondria was correlated with the change in
V̇O2peak (9). Therefore, we can presume that for after-MI
patients, deconditioning effects in skeletal muscle of MI may
be present for approximately 20 d after the onset of MI in the
present study. However, a possibility that deconditioning ef-
fects have already occurred before onset of MI may remain,
as Marchionni et al. (18) reported that V̇O2peak in 4–6 wk after
MI is related to usual physical activity before MI. Further-
more, the magnitude of deconditioning effects during inac-
tivity may be partly affected by the initial V̇O2peak before
inactivity. Hence, muscle deoxygenation responses and their
relation to peak aerobic capacity should be confirmed in patients
Medicine & Science in Sports & Exercised 2067
 before onset of MI. Although this area warrants further in-
vestigation, the present study is the first study to demonstrate
that the dynamic oxygen imbalance in exercising muscles is
CLINICAL SCIENCES
related to peak aerobic capacity in early post-MI patients.
We also observed differences in cardiorespiratory vari-
ables between MI and CON during submaximal and peak
exercise. During submaximal exercise, V̇O2 was 15%–18%
lower in early post-MI patients. The possible explanations
for this lower V̇O2 in MI are that the fundamental link be-
tween muscular energy expenditure and power output (i.e.,
cycling efficiency) is somehow altered in MI and/or that
V̇O2 kinetics are slow, consequent to low muscle O2 supply
or muscle oxidative capacity (20). Poole et al. (25) also
pointed out that lower V̇O2 at a given absolute WR in CHF
‘‘should not be taken as evidence that patients with CHF
are working more efficiently’’. Moreover, a previous review
(28) suggested that during low-intensity exercise, the reason
for lower V̇O2 may be that ‘‘O2 utilization in patients is less
able to keep pace with the demands of the ramp exercise’’.
In the present study, the whole slope of $V̇O2/$WR from
4 min after the beginning of the ramp loading up to the point
at which the slope deviates from linearity was not different
between groups, and the MRT was longer in MI patients.
Therefore, these results may lead us to speculate that the
lower V̇O2 is mainly caused by the slower V̇O2 kinetics,
and therefore, phosphocreatine breakdown and/or glycoly-
sis compensate for the difference in V̇O2. However, a low
number of data points was calculated to estimate the $V̇O2/
$WR slope and MRT in a low number of subjects. More-
over, we should recognize that the back-extrapolation
method to estimate the MRT can also be complicated be-
cause of internal work, especially when using low baseline
WR (5). Future study is needed in a larger number of subjects.
In addition, HRmax was significantly lower in MI patients,
and the lower HRmax in post-MI was likely to contribute to
reduced peak aerobic capacity. Previous studies have clearly
demonstrated that beta blockers attenuate the HR response
during submaximal and peak exercise (12), and 75% of MI
patients took beta blockers in this study. However, HR re-
sponses were similar between groups during submaximal
exercise. One possible point of speculation for the nonsig-
nificant difference in HR response between MI and CON
is higher HR response in MI when beta blockers are not
administered. On the basis of the speculation, we hypothe-
size that beta blockers attenuated HR response in MI. As a
result, in the present study, HR response during submaximal
exercise did not differ between MI and CON.
We recognize that there is an absence of deep femoral
venous oxygen saturation, cardiac output, muscle blood flow
measurements, and muscle biopsy to support our findings.
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2068 Official Journal of the American College of Sports Medicine
Copyright © 2014 by the American College of Sports Medicine. Unauthorized reproduction of this article is prohibited.
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The authors are grateful for the revision of this manuscript by
Andrea Hope. We also thank Tsubasa Watanabe, Miwako Tanabe,
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This work was supported in part by grant-in-aid for scientific re-
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