Jpn Circ J 1999; 63: 843-848

Effects of Exercise Training on the Recovery of theAutonomic Nervous System and Exercise Capacity
After Acute Myocardial Infarction
Misa Oya, MD; Haruki Itoh, MD*; Kazuzo Kato, MD*;

Kazuhiko Tanabe, MD; Masahiro Murayama, MD

This study investigated the effects of aerobic exercise training on the early phase of the recovery process follow
ing acute myocardial infarction (AMI) in terms of the autonomic nervous system, cardiac function and exercise
capacity. Twenty-eight patients in the first week after the onset of AMI were assigned randomly to either a train
ing group or a control group. The training group performed aerobic exercise for 2 weeks. Cardiopulmonary exer
cise testing was performed 3 times during the 3 months after the onset. Heart rate variability, plasma norepinephrine (NE) levels, and cardiac index (CI) during exercise were measured. In the training group, plasma NE level
and ACI (peak Cl-rest CI) were significantly improved from 1 to 3 weeks after the onset, and the high frequencyof heart rate variability and peak oxygen uptake were significantly increased up to 3 months after the onset. In
the control group, the plasma NE level and the ACI during the 1-3 weeks post-AMI, the high frequency of heart
rate variability and the peak oxygen uptake showed a tendency to improve up to 3 months after the onset. These
results indicate that sympathetic nervous activity improves soon after the onset of AMI, in conjunction withimprovement in cardiac function, and that this improvement is not affected by exercise training. In contrast, therecovery of parasympathetic nervous activity requires a longer period, along with the recovery of exercise capac
ity, which is facilitated by even short-term aerobic exercise training. (Jpn Circ J 1999; 63: 843-848)

Key Words: Autonomic nervous system; Exercise training; Heart rate variability; Myocardial infarction

Several studies have shown a decreased heart rate(HR) response during exercise in patients withcoronary artery disease and heart failure.'-3
Diminished HR variability could be a useful prognostic
indicator after myocardial infarction (MI) and have a
predictive value independent of conventional noninvasive
measurements, such as exercise time, late potential, or
detection of ventricular ectopy by Holter monitoring?-6
Parasympathetic nervous activity is suppressed and sympa
thetic nervous activity is accentuated after acute MI

nervous activity even in healthy subjects6-7 However, little
information is available about the effect of exercise train
ing on the recovery process of the autonomic nervous
system and on exercise capacity in the early phase after
AMI. We designed this study to investigate the detailed
time courses of the recovery process of both parasympa
thetic and sympathetic nervous activity, as well as cardiac
function reserve, during exercise and to clarify the effectsof early physical training on the recovery course of thosefunctions in patients with AMI.

(AMI).1-2 However, the detailed time course of the recovery
process of this autonomic nervous imbalance in patients inthe acute phase of MI is not clear.
Aerobic exercise training improves exercise capacity inhealthy subjects6-7 and even in patients with AMI?-"
Recent studies have shown that physical training improvesautonomic nervous activity and decreases the incidence of
cardiac events or sudden death not only in patients with
AMI, but also in those with chronic heart failure,12-13 andthat physical training may increase parasympathetic(Received April 22, 1999; revised manuscript received July 15, 1999;
accepted July 21, 1999)
Department of Internal Medicine, St Marianna University School of
Medicine, Kanagawa and *The Cardiovascular Institute, Tokyo,
Japan
This work was presented in part at the 69th Scientific Session of theAmerican Heart Association, New Orleans, Louisiana, November
1996 and at the XVDIth European Society of Cardiology Meeting,Stockholm, Sweden, August 1997.
Mailing address: Misa Oya, MD, Department of Internal Medicine,
St Marianna University School of Medicine, 2-16-1 Sugao, Miyamaeku, Kawasaki, Kanagawa 216-8511, Japan
Japanesc Circulation Journal

Vol.63, November 1999

Methods
Subjects
Twenty-eight patients (59.0±6.0 years old, mean±SD)

were enrolled in the study 1 week after the onset of AMI.
The diagnosis of AMI was made on the basis of chest pain
persisting for at least 30min, an ST-segment elevation of atleast 0.1 mV in at least 2 contiguous leads and elevation ofserum creatine kinase-MB (CK-MB) to more than twice
the upper limit of the normal range. Their clinical characteristics, including age, site of infarction, ejection fraction,and mean peak creatine kinase level, are summarized inTable 1. During the acute phase, prior to entering the study,
25 patients underwent direct percutaneous transluminal
coronary angioplasty and/or percutaneous transluminal
coronary revascularization and 3 underwent conservative
therapy. We excluded patients with severe heart failure or
arrhythmia (atrial fibrillation, bundle branch block,frequent extrasystole) or with ST depression more than 0.2
mV during an exercise test. During the investigation,
medications were not changed in order to prevent any influ-

OYA M et al.

844

Table 1

Patient Characteristics
Training group

Control groupAge (years)

59±7

58±7

Sex(M/F)

14/2

12/0

Anterior

20Anteroseptal

8

Inferior

56Lateral

2

1

NS
NS

Site of infarction

Posterior
LVEF(%)

CKmaxOU/L)

3

NS

1

0

63±8

62±12

NS

2445±226I

242711824

NS

Results are expressd as mean+SD or number ofpatients.
LVEF, left ventricular ejection fraction; CK, creatine kinase; NS, notsignificant; training group vs control group.

ence on the exercise response. The study was approved by
the hospital ethics committee of The Cardiovascular
Institute Hospital, and after detailed explanation of thestudy protocol, informed consent was obtained from all
subjects.

Study Protocol
All patients enrolled in this study underwent cardiopulmonary exercise testing with expired gas analysis 1 week
after the onset of AMI. Cardiac output was measured by
the dye dilution method. The patients were randomly
assigned to either a training or a control group. The training
group consisted of 14 men and 2 women, the control group
12 men. The training group performed supervised exercise
training using a cycle ergometer at the anaerobic thresholdlevel for 30min, twice daily for 2 weeks. In the control
group, only walking exercise was permitted according to aconventional rehabilitation protocol. Then, 3 weeks after
the onset of AMI, patients in both groups underwent
cardiopulmonary exercise tests to evaluate exercise capac
ity, cardiac output, and autonomic nervous activity during
exercise. They were discharged after completion of eachrehabilitation program for the acute phase of MI. They
performed the same tests again at 3 months after the onset.

and that for CO2 as VE/VCO2, and the gas exchange ratio
as VCO2/VO2. These parameters were simultaneously
displayed on a monitor of a personal computer (PC-9821,
NEC, Tokyo, Japan). The anaerobic threshold was deter
mined by the following conventional criteria: (1) VE/VO2
increased after being constant or decreased while
VE/VCO2 remained constant or decreased and (2) the gas
exchange ratio, which had been stable or slowly rising,began to increase more steeply. Peak VO2 was calculated,by averaging the values recorded during the final 30 s of aramp exercise.
Time Constant ofVOi
To determine VO2 kinetics at the beginning of exercise,the time constant was calculated from the start of exercise
with single exponential kinetics using least square nonlin
ear regression analysis; the resting value was designated as
its baseline and the VO2 at the end of the warm-up period
as its asymptote.

Blood Sampling
Plasma norepinephrine (NE) level, which could repre
sent sympathetic nervous activity, was measured at the endof the warm-up. The sampled blood was ice-cooled imme
diately and centrifuged at 3000 rpm for 10 min at 4°C,
thereby separating the plasma, which was frozen and stored
at -70°C until the day of analysis. Norepinephrine was
extracted by alumina absorption and then measured byhigh-pressure liquid chromatography.
Power Spectral Analysis of Heart Rate Variability
Spectral analysis of the HR variability was performed
according to the methods of Yamamoto and Hughson,14 andthe data were analyzed by Fast Fourier Transform. Spectral
HR variability was expressed as low frequency (LF:
0.04-0.15 Hz) and high frequency (HF: 0.15-0.8 Hz)
components. HF was used as an index of parasympathetic
nervous activity in this study. The power spectrum data of
the continuous time sequence of R-R intervals were calcu
lated after 3 min of resting, during warming-up with the
exception of the first minute, and then every 2 min during
incremental exercise.

Exercise Testing

Symptom-limited exercise testing using a ramp protocol(1 W/6s) with a cycle ergometer (CPE 2000, MedGraphics
Co, Minneapolis, MN, USA) was performed at 1 week, 3weeks, and 3 months after the onset of AMI. After a 4-min
rest on the cycle ergometer, exercise began with a 4-minwarm up at 20 W followed by continuous load increase oflOW/min. HR, ST-T changes, and arrhythmia were moni
tored by 12-lead electrocardiogram using a model ML5000 Stress Test System (Fukuda Denshi, Tokyo, Japan)
throughout the tests. Blood pressure was also measured at 1
min intervals by the cuff method using an automaticmanometer (STBP-780, Colin Denshi, Aichi, Japan).
Ventilatory Gas Analysis
Ventilatory gas exchange was measured on a breath-bybreath basis with a gas analyzer (Aerometer AE-280s,
Minato Medical Science Co, Osaka, Japan). The system
was carefully calibrated before each study. Oxygen uptake(VO2), carbon dioxide output (VCO2) and minute ventila
tion (VE) were measured on a breath-by-breath basis
throughout the testing. From these measurements, theventilatory equivalent for VO2 was calculated as VE/VO2

Cardiac Output
The cardiac index (CI) was measured at rest and during
exercise by the dye dilution method using a dye densitometer (MCL-4200, Nihon Koden, Tokyo, Japan).15 A catheter
was placed in the left brachial vein, and indocyanine green(5 mg) was injected from the catheter during the resting
control state, the warm-up state, and the peak exercise
state. The change in CI (ACI) from resting to peak exercise
was calculated as an index of cardiac output reserve.
ACI = (peak value)-(resting value)
Statistical Analysis
The mean values of parameters in the 2 groups werecompared by unpaired Student's t test. The time coursechanges of the ventilatory parameters and cardiac output
during exercise were analyzed by one-way ANOVA of
repeated measurements. When this test was significant, apost-hoc test (Fisher's PLSD) was used to compare eachmeasurement. A value of p<0.05 was considered signifi

cant. HF data are expressed as mean±SE. The other data
are expressed as mean±SD.
Japanese Circulation Journal

Vol.63, November 1999

Exercise Training and Autonomic Nervous Activity After. MI

845

(A)
Peak VO.,(ml min-'kg"1) 'p<0.0523 -(B)
p<0.05

Delta value of

/

21 -

^#—

19"

18"

cV"—

---0 Control

1

1

16"

^j^ Training
W group
1

i

17"

group

1

■

K

h Training
group

4.5-

H Control

4.0.

group

1 K

J.J -

3.0-

2.01.5.

15-

1.0-

p < 0.05

^!7I

0.5 .

13:

mean ± SDn J
1 weekFig 1.

•

2.5-

1

i

14"

t

5.0^

|

22'

20-

peak VO2(ml mm'1 kg"1)

3 weeks

10.

3 monthsI■M

1-3 weeks'' 1:"|mean±SD

3 weeks -3 months(A) Serial change in peak oxygen uptake (VO2) and (B) the delta value of tfO2 from 1 week to 3 months after the onset of acute myocardial

infarction (AMI) in the training and control groups. Peak V62 increased significantly in the training group from 1 to 3 weeks post-AMI.
(B)

(A)

Delta value of A CI

A CI

(Lmhr'nr2)

p<0.05I(Lmur'nr2)

p<0.05Training
group

Control

7 .

group

Training
group

Control

5 .

group

4 .

mean±SD3 .

mean ± SD
1 week3 weeks

3 months

3 weeks -3 months

1 -3 weeks

Fig 2. (A) Changes in the cardiac index (ACI) from 1 week to 3 months after the onset of acute myocardial infarction (AMI) in the training andcontrol groups and (B) the relationship between delta values of these groups. ACI increased significantly in the training group, and the change in
ACI in the training group was greater than that in the control group from 1 to 3 weeks post-AMI.

(B)
Delta value of HF

p<0.05

at20W

HF at 20 W

Training

(ms*)

group

35 1

120 -

Control

110-

group

100 -

Training

90 -

group

8070-

Control

60 -

group

50 40 30 -mean±SEmean ± SE0

1 week3 weeks

3 months

1 -3 weeks

3 weeks -3 months

Fig 3. (A) The change in high frequency (HF) and (B) the delta value of HF at 20 W from 1 week to 3 months after the onset of acute myocardial
infarction (AMI) in the training and control groups. HF increased in both groups from 1 week to 3 months post-AMI, but significantly so in the
training group.

Japanese Circulation Journal

Vol.63, November 1999

OYA M et al.

846

(B)

(A)
Delta value of NE
at 20 VV
(ng/ml)NEat20W(ng/ml)Training

0.2 t

group

0.65 ■

Control
0.1 -0.55 -

group

Control

0.45

group

Training

0.35 ■

mean±SD•0.1 -

group0.25 -

0.15 ■

p<0.05mean ± SD
1 week3 weeks

3 weeks -3 months

1 -3 weeks

3 months

Fig 4. (A) The change in the blood concentration of norepinephrine (NE) and (B) the delta value of NE at 20 W from 1 week to 3 months after the
onset of acute myocardial infarction (AMI) in the training and control groups. NE level decreased in both groups from 1 to 3 weeks post-AMI, but
significantly so in the training group.

(B)

(A)
Time constant

Delta value of time

constant of VO 2
65 -

0 -

60 55 -

-5 •

■

1

h Training

50 -Control

45 ■

group

-10 -

(HO Control

group

40 ■

Training

35 •

group

-15 ■

group

30

-20 -

mean±SD

25 H

mean ± SD0

1 weekFig 5.

I

3 weeks

3 months-25 ■1-3 weeks

3 weeks -3 months(A) Change in and (B) delta value of the time constant of VOz from 1 week to 3 months after the onset of acute myocardial infarction(AMI) in the training and control groups. The time constant of v"O2 was significantly shortened from 1 to 3 post-AMI in the training group.

Results
During the study period, none of the patients sufferedfrom major complications, such as worsening of heart
failure, sudden cardiac death or any other cardiac event.
Change in Peak Exercise Capacity

Peak VO2 increased from 1 week to 3 months after the

onset of MI in both the training and control groups. The
increase from 1 to 3 weeks was significant in the training
group (17.6±3.1 to 19.8±2.9ml min-'kg"1, p<0.05),
whereas no significant change was noted in the control
group. From 1 to 3 weeks, the mean delta value of peakVO2 in the training group was greater than that in thecontrol group (2.2±2.8 vs l.tol.Smlmur'kg-1), although
this difference was not statistically significant (Fig 1). Peakwork rates (W/kg) in the training group were 74.6±16.7 at
1 week, 90.5±16.2 at 3 weeks and 93.5±18.0 at 3 months
W/kg, and 72.3±14.9 at 1 week, 80.8±16.7 at 3 weeks and86.1+19.3 at 3 months W/kg in the control group. It
increased significantly from 1 to 3 weeks in the training

group (p<0.05), whereas significant change was noted in
the control group from 1 week to 3 months (p<0.05).
Change in Cardiac Index
From 1 to 3 weeks post-AMI, ACI increased significantlyin the training group (4.6±1.5 to 5.8±1.7ml min-1 nr2,
p<0.05), but not in the control group (Fig 2). The change in
ACI from 1 to 3 weeks post-AMI was significantly higher
in the training group than in the control group (1.2±0.9 vs0.4±0.4ml min-1 nr2 p<0.05). There was no significant
difference in ACI between the groups in the period from 3
weeks to 3 months post-AMI.
HF During Exercise at 20 Watts
HF increased in both the training and control groups, andthis increase from 1 week to 3 months post-AMI was

significant in the training group (55±8 to 106±31, p<0.05
vs 48±6 to 66±14 ms2 in the control group). The delta valueof HF at 20 W from 1 to 3 weeks post-AMI was signifi
cantly higher in the training group (30±6 vs 10±8ms2,
p<0.05), whereas the values obtained from 3 weeks to 3
Japanese Circulation Journal

Vol.63, November 1999

Exercise Training and Autonomic Nervous Activity After MImonths post-AMI were not statistically different between
the groups (Fig 3).
Plasma Norepinephrine Level at 20 Watts
Although both groups showed decreases in plasma NE at
20 W exercise during the 1-3 weeks post-AMI period, thedecrease was only significant in the training group (from0.5±0.2 to 0.3±0.1ng/ml, p<0.05). The decrease in NE
level did not differ significantly between groups throughout
the study (Fig 4).

Time Constant of VO2
The time constant of VO2 was significantly shortened
from 1 to 3 weeks post-AMI in the training group(49.8±13.0 to 40.0±13.3, p<0.05), whereas it did notchange significantly in the control group. The delta value ofthe time constant of VO2 showed no significant difference
between the groups throughout the investigation (Fig 5).

Discussion
It has been recognized that the sympathetic nervous
system and the parasympathetic nervous system contend
widi each other and that a balance between them may be an
important factor in the onset of ischemic heart disease andarrhythmia. Within the cardiac autonomic nervous system,
the parasympathetic nervous system has been paid lessattention compared with the sympathetic nervous system in
relation to ischemic heart disease because the difficulty of
its evaluation. Since a technique for evaluating HR variability and baroreflex sensitivity was established in the
1980s, the role of the parasympathetic nervous system inassociation with coronary artery disease has been investi

gated.16-17 The prognostic value of HR variability was firstreported in a cohort of patients with MI.18 In that study, therelative risk for mortality was 5.3 times higher in patientswith lower HR variability assessed in time domain
measures from measurements taken over a 31-monthfollow- up. Wolf et al reported that patients with HR variability less than 32ms had a significantly higher hospitalmortality rate than those with a variability higher than 32
ms.19 In their report of 176 patients with AMI, HR variabil
ity measured on the day of admission to the coronary careunit was a useful index as for predicting their mortality.
Reportedly accelerated sympathetic nervous activity leads
to a cardiac electrophysiological imbalance and facilitates
the occurrence of fatal arrhythmia?0 However, theparasympathetic nervous system may protect against thiscardiac electrophysiological imbalance and against sudden
cardiac death or fatal arrhythmia?1'22 Despite the wellknown benefits of exercise training on exercise capacity
after MI, little data are available on the effects of exercise
training on the sympathetic nervous system/parasympa
thetic nervous system balance.
Recovery of the Autonomic Nervous System,
Exercise Capacity and Cardiac Function
The present study was conducted during the early phaseof MI to investigate the effects of supervised exercise train
ing upon autonomic nervous activity and cardiac function.
In the present study, although both sympathetic nervous
activity and parasympathetic nervous activity improved
during the investigation, the rate of recovery for each wasdifferent. The sympathetic nervous system improved
during the first 3 weeks after the onset of MI, whereas theJapanese Circulation Journal

Vol.63, November 1999

847

parasympathetic nervous system improved graduallyduring the 3-month study. Cardiac function during exercise
also improved during the initial 3 weeks, whereas exercise
capacity improved gradually throughout the observation
period, similar to the recovery process of the parasympa
thetic nervous system. Both the training and control groups
showed similar time courses regarding the recovery of boththe sympathetic and parasympathetic nervous systems.
The parasympathetic nervous system is known to be
predominant during the resting state in the healthy human.
In heart failure patients, it is suspected that the parasympa
thetic nervous system is initially suppressed to preserve
cardiac function, and the sympathetic nervous system is
activated as the degree of heart failure worsens. In thepresent study, the sympathetic nervous system was acti
vated and the parasympathetic nervous system was
suppressed during the acute phase of MI, consistent withheart failure patients in previous reports. Bigger et alreported that from 1 week to 2 months after the onset ofMI, all spectral components (LF and HF) of the HR variability of patients decreased one-third to one-halfcompared with healthy subjects23 All components also
improved remarkably during the first 3 months after the
onset of MI and then increased slightly from 3 to 12
months. However, even at 1 year after the onset, all compo
nents were about one-half to one-third that of healthy
subjects. In another study, exercise training improved
parasympathetic nervous activity along with increasing
exercise capacity in healthy men? In the present study, thesympathetic nervous activity improved soon after the onset
of MI in conjunction with the improvement in cardiac function, whereas improvement in the parasympathetic nervous
activity required a longer time during which exercise
capacity also increased. This observation is consistent withthe reversed image in the changes in autonomic nervous
activities that occur with worsening of heart failure.
Effects of Physical Training on Cardiac Function
and the Autonomic Nervous System
Currently, physical training is recommended for patients
after AMI, as well as for patients with other cardiac
diseases. Some reports12'24 have shown beneficial effects ofexercise training in the chronic phase of MI. These benefi
cial effects have been demonstrated even in patients withseverely depressed ventricular function and chronic heart
failure25"27 and have been attributed to peripheral adapta
tions that result in greater oxygen utilization in the skeletal
muscles. Several reports have shown that exercise training
increased maximal exercise capacity and endurance capac
ity in patients with MI?-1 !'28 In the present study, peak VO2increased significantly in the training group. The CI during
exercise also increased significantly in the training groupduring the early phase after the occurrence of AMI. Coatset al reported that exercise training increases cardiac output
during exercise in patients with stable, moderate-to-severe
chronic heart failure caused by ischemic heart disease.12
Our present findings would support the hypothesis thatexercise training during the early phase following AMI canbe effective in increasing exercise tolerance by improving
the cardiac output response during exercise. In addition, thefavorable effects were maintained at 3 months after the
onset of MI, although no special program was prepared for
either group after discharge.
A few studies have addressed the issue of the relation
between exercise training and autonomic nervous activity

OYA M ec al.

848

during the chronic phase of MI. Hull et al reported thatexercise training increased the sensitivity of baroreceptor
reflexes and suppressed the occurrence of ventricular fibril
lation induced by exercise in the high-risk dog withischemic heart disease?9 This suggests that exercise train
ing may not only increase the reflex of the parasympathetic
nervous system, but also suppress the sympathetic nervous
system in ischemic heart disease. Several reports havenoted that many secondary abnormalities associated withchronic heart failure may reflect physical deconditioning,12-13-24 which itself may be partly responsible for someof the associated abnormalities and exercise limitation's ofchronic heart failure, including abnormalities in autonomic
balance. Other reports have described increases inparasympathetic nervous activity as a result of exercise

training, even in healthy men?-7 In the present study, theparasympathetic nervous system and sympathetic nervous
system of the training group were both improved signifi
cantly compared with the control group, and the anaerobic

threshold level training had no adverse effects in the recov
ery process of cardiac function or autonomic nervous activ
ity. As a result, improving the HR variability imbalance by
aerobic exercise training during the early phase after MI
may contribute to a decrease in mortality. These results
indicate that anaerobic threshold level exercise training canbe useful for increasing the exercise capacity in patients inthe early phase of MI. Consequently, these results support
the hypothesis that anaerobic threshold level exercise train
ing can decrease die mortality rate by improving the auto
nomic nervous activity imbalance in patients with ischemic
heart disease.
Regarding the serial changes in the measured parame
ters, both cardiac function and sympathetic nervous activity
improved soon after the onset of AMI, and this improvement was not affected by exercise training. In contrast, therecovery of parasympathetic nervous activity requires alonger period, along with the recovery of exercise capacity,which is facilitated by even short-term aerobic exercise
training. In conclusion, aerobic exercise training results inimprovement of cardiac reserve and autonomic nervous
imbalance during the early phase of AMI.

7.

8.

al: Interaction between exercise training and ejection fraction inpredicting prognosis after a first myocardial infarction. Circulation
9.

10.

11.

12.

13.

14.

3.

4.

5.

6.

Komatsu E, Yamaguchi 1, Miyazawa K: Reliability of cardiac output
measurement during supine exercise by using earpice densitometer.

18.

19.

variability and its association with increased mortality after acute
myocardial infarction. Am J Cardiol 1987; 59: 256-262
Wolf MW, Varigos GA, Hunt D, Sloman JG: Sinus arrhythmia in

17.

20.

21.

23.

2.

Rousseau MF, Degre S, Messin R, Brasseur LH, Denolin H, Detry JM: Hemodynamic effects of early physical training after acute
myocardial infarction: Comparison with a control untrained group.
Eur J Cardiol 1974; 2: 39-45
Coats AJS, Adamopoulos S, Radaelli A, McCance A, Meyre TE,
Bernardi L, et al: Controlled trial of physical training in chronic heart
failure: Exercise performance, hemodynamics, ventilation, and auto
nomic function. Circulation 1992; 85: 2119-2131
Kiilavuori K, Toivonen H, Naveri H, Leinonen H: Reversal of auto
nomic derangements by physical training in chronic heart failure
assessed by heart rate variability. Eur Heart J 1995; 16:490-495
Yamamoto Y, Hughson RL: Coarse graining spectral analysis: New
method for studying heart rate variability. J Appl Physiol 1991; 71:

Kokyu to Junkan 1985; 33: 285-288
Kjellgren O, Gomes JA: Heart rate variability and baroreflex sensi
tivity in myocardial infarction. Am Heart J 1993; 125: 204-215
Huikuri HV: Heart rate variability in coronary artery disease. J
Intern Med 1995; 237: 349-357
Kleiger RE, Miller JP, Bigger JT, Moss AJ: Decreased heart rate16.

We thank Mr Yoshio Nakamura for his assistance in measuring theheart rate variability. We also thank Miss Naomi Ohta, Miss Tomoko
Maeda, and MrAkihiko Tajimafor their technical assistance.

Ecberg DL, Drabinsky M, Braunwald E: Defective cardiac parasym
pathetic control in patients with heart disease. N Engl J Med 1971;
285: 877-883
Ryan C, Hollenberg M, Harvery DB, Gwynn R: Impaired parasym
pathetic responses in patients after myocardial infarction. Am J
Cardiol 1976; 37: 1013-1018
Bristow JD, Honour AJ, Pickering GW, Sleight P, Smyth HS:
Diminished baroreflex sensitivity in high blood pressure. Circulation
1969; 39:48-54
Kleiger RE, Miller JP, Krone RJ, Bigger JT: The independence ofcycle length variability and exercise testing on predicting mortalityof patients surviving acute myocardial infarction. Am J Cardiol
1990; 65:408-411
Farrell TG, Bashir Y, Cripps T, Malik M, Poloniecki J, Bennett ED,
et al: Risk stratification for arrhythmic events in postinfarction
patients based on heart rate variability, ambulatory electrocardiographic variables and the signal-averaged electrocardiogram. J Am
Coll Cardiol 1991; 18: 687-697
Goldsmidi RL, Bigger JT Jr, Steinman RC, Fleiss JL: Comparison of

Exercise in Anterior Myocardial Infarction (EAMI) trial. J Am Coll
Cardiol 1993; 22: 1821-1829
Barletta GA, Fattirolli F, Bisi G, Bertini G, Malfanti PL, Gallini C, et
al: Short-term responses to cardiac rehabilitation after acute myocar
dial infarction: Cardiac function evaluation before and after physicaltraining at rest and during stress test. Eur Heart J 1983; 4: 761-772

1143-1150

15.

22.

J.

1996; 94: 978-982
Giannuzzi P, Tavazzi L, Temporelli PL, Corra U, Imparato A,
Gattone M, et al: Long-term physical training and left venUkuVai

remodeling after anterior myocardial infarction: results of theA cknowledgments

References

24-hour parasympathetic activity in endurance-trained and untrained
young men. J Am Coll Cardiol 1992; 20: 552-558
Molgaard H, Sorensen KE, Bjerregaard P: Circadian variation andinfluence of risk factors on heart rate variability in healthy subjects.
Am J Cardiol 1991; 68: 777-784
Specchia G, De Servi S, Scire A, Assandri J, Berzuini C, Angoli L, et

24.

25.

26.

27.
28.

29.

acute myocardial infarction. MedJAust 1978; 2: 52-53
Myerburg RJ, Kessler KM, Mallon SM, Cox MM, Marchena E,
Interian A, et al: Life-threatening ventricular arrhythmia in patientswith silent myocardial ischemia due to coronary artery spasm. N
Engl J Med 1992; 326: 1451 -1455
Billman GE, Hoskins RS: Time-series analysis of heart rate variabil
ity during submaximal exercise: Evidence for reduced cardiac vagal
tone in animals susceptible to ventricular fibrillation. Circulation
1989; 80: 146-157
Vanoli E, De Ferrari GM, Stramba-Badiale M, Hull SS Jr, Foreman
RD, Schwartz PJ. Vagal stimulation and prevention of sudden deathin conscious dogs with a healed myocardial infarction. Circ Res
1991; 68: 1471-1481
Bigger JT Jr, Fleiss JL, Rolnitzky LM, Steinman RC, Schneider WJ:
Time course of recovery of heart period variability after myocardial
infarction. J Am Coll Cardiol 1991; 18: 1643-1649
La Rover MT, Martara A, Sandrone G, Lombardi F: Autonomic
nervous system adaptations to short-term exercise training. Chest
1992; 101: 299S-303S
Ehsani AA, Biello DR. Schultz J, Sobel BE, Holloszy JO:
Improvement of left ventricular contractile function by exercise
training in patients with coronary artery disease. Circulation 1986;
74: 350-358
Tavazzi L, Ignone G: Short term haemodynamic evolution and latefollow-up of post infarct patients with left ventricular dysfunction
undergoing a physical training programme. Eur Heart J 1991; 12:657-665
Coats AJS, Adamopoulos S, Meyer TE, Conway J, Sleight P: Effectsof physical training in chronic heart failure. Lancet 1990; 335: 63-66
Ehsani AA: Mechanisms responsible for enhanced stroke volume
after exercise training in coronary heart disease. Eur Heart J 1987;
8(Suppl G): 9-14
Hull SS Jr, Vanololi E, Adamson PB, Verrier RL, Foreman RD,

Schwartz PJ: Exercise training confers anticipatory protection fromsudden death during acute mvocardial ischemia. Circulation 1994;
89:548-552

Japanese Circulation Journal

Vol.63, November 1999