Vol.5, No.10, 1706-1711 (2013) Health
http://dx.doi.org/10.4236/health.2013.510230
The effect of aerobic training on
endothelium-dependent vasodilatation
in patients with coronary artery disease
who were revascularized and young men
Seyed Masoud Seyediyan, Farzaneh Ahmadi*, Babak Hamidian, Ebrahim Hajizadeh,
Afshin Rezazadeh, Ahmad Reza Asare, Mohammad Hasan Adel, Mohammad Nourizadeh
Department of Cardiology, Medical Joundishapour University of Ahvaz, Atherosclerosis Research Center Jondishapour University of
Medical Sciences, Ahvaz, Iran; *Corresponding Author:
Received 13 April 2013; revised 15 May 2013; accepted 19 June 2013
Copyright © 2013 Seyed Masoud Seyediyan et al. This is an open access article distributed under the Creative Commons Attribution
License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
ABSTRACT
Aim: The aim of this study was to determine the
effect of training on endothelium-dependent
vasodilatation in patients with coronary artery
disease (CAD) after revascularization and heal-
thy young men. Background: Impaired endothe-
lial function has been observed in patients with
CAD and those with CAD risk factors. Studies
have show n that exercise can enhance endothe-
lial function. Methods: This experimental cross-
sectional study was conducted on patients with
CAD (3 months after CABG and PCI) and students
of medical school in 2011. Endothelium depen-
dent dilation of the brachial artery was deter-
mined by using high-resolution vascular ultra-
sonography through flow-mediated vasodilata-
tion (FMD) after induction of ischemia, and the
data were analyzed using SPSS, dependent t-
test and ANCOVA. Findings: The findings show -
ed that at baseline, FMD was reduced in revas-
cularized patients, when compared with healthy
young men, after 8 weeks, and exercise training
significantly improved FMD in patients under-
went training group [from 4.31 ± 1.45 (SD)% to
6.15 ± 0.773 (SD)%, p < 0.05] and substantially
increased the same in healthy young men [from
9.18% ± 1.45% to 11.72% ± 1.72%, p < 0.05]
However, in the control group, the FMD remain-
ed unchanged, and even after aerobic training,
it did not significantly modif y the brachial artery
diameter in these group s. Conclusion : Our study
demonstrates that endothelial dysfunction per-
sisting in CAD patients after revascularization
and aerobic training can improve endothelial
function in different vascular beds in CAD pa-
tients and healthy young men. This may contri-
bute to the benefit of reg ular exercise in pr event-
ing and restricting cardiovascular disease.
Keywords: Endotheli um-Dependent Vasodilatation;
Coronary Artery Disease; Aerobic Training;
High-Resolution Ultrasound;
Flow-Mediated Dilation
1. INTRODUCTION
Currently, most patients with angina pectoris have
their symptoms controlled with medication or by revas-
cularization by PTCA or CABG. Consequently, and with
rare exceptions [1], much of the evidence that exercise
training improves effort tolerance in patients with angina
pectoris was obtained before 1990. Exercise training
increases the exercise time to the onset of angina or even
eliminates angina entirely by at least two mechanisms.
First, exercise training reduces the M.O2 requirements
during submaximal exercise [1-3]. Second, exercise train-
ing reduces endothelial dysfunction [4-6]. Normal coro-
nary arteries dilate with exercise, whereas atherosclerotic
coronary arteries often demonstrate endothelial dysfunc-
tion evidenced by exercise-induced vasoconstriction. Few
large trials have examined the effects of exercise-based
cardiac rehabilitation in patients following PTCA [6,7].
There are very few data for coronary artery disease
and healthy young men. In a previous study, we demon-
strated that in healthy middle age men, 8 weeks of circuit
training did not affect vascular function [8], whereas, bra
chial artery flow mediated dilation (FMD) was enhanced

S. M. Seyediyan et al. / Health 5 (2013) 1706-1711 1707
after a 10 weeks programme of daily aerobic and anaero-
bic exercise training in young military recruits [9], also
in CAD patients who had had a recent acute myocardial
infarction. Aerobic training significantly improved endo-
thelial function, although this beneficial effect was lost
after 1 month of detraining [10]. In addition, regular
aerobic physical training enhanced vascular function in
patients with chronic heart failure [11]. However, there is
very little knowledge about a similar benefit from resis-
tance training on CAD revascuralized patients and heal-
thy young men.
Therefore, in this study, we have investigated the ef-
fects of an 8-week aerobic training program on systemic
artery vascular function in coronary artery disease (CAD)
patients who have been treated and don’t have apparent
ischemia, and compared the results with the same of
young men, and have demonstrated which is the most
significant improvement in endothelium dependent dila-
tion in all groups.
2. METHODS
2.1. Subjects
The study included 20 men with a history of CAD
from heart clinic of medical science hospital and they
were divided to 10 cases and 10 control groups. The in-
clusion criteria were as follows: the patients must be
known case of CAD, and underwent regular surgical (co-
ronary artery bypass grafting) or non-surgical revascu-
larization (percutaneous transluminal coronary angio-
plasty) with normal or near normal left ventricle ejection
fraction, more than recent 3 month.
On the other hand, patients who had valvular heart dis-
ease, chronic obstructive lung disease, renal and hepatic
dysfunction, asthma, creatinine > 2.5 mg/dl and subjects
performed more than two sessions of light to moderate
exercise per week, were excluded week. Medications did
not change across the course of control or exercise train-
ing periods. Furthermore, 10 young age healthy male
subjects without cardiovascular disease and risks factors
were randomly selected among the students of a medical
school.
The characteristics of revascularization patients and
healthy young subjects enrolled in the study are present-
ed in Table 1. The ethics committee approved the proto-
col and all the subjects gave written informed consent.
2.2. Study Design
All subjects underwent baseline assessment, after
which CAD patients and young men were randomly as-
signed to either remain sedentary or undergo exercise
training for 8 weeks according to the following protocol,
and after 2 months, the assessment was repeated. Pa-
tients and young men were requested to maintain their
diet and other life style behavior for the duration of the
study, and this was confirmed through interview and
questionnaire.
Assessment of vascular function was carried out in a
quiet, temperature-controlled laboratory after an 8-h fast,
12-h abstinence from caffeine, and 24-h abstinence from
alcohol and exercise. For individual subjects, repeat as-
sessments were performed at the same time of the day,
and the time of medication use was not changed. Endo-
thelial function was assessed using a noninvasive tech-
nique proposed by Celermajer et al. [6]. The subjects
were made to rest in supine with nondominant arm ex-
tended and immobilized with foam supports at an angle
of 80˚ from the torso, the heart rate was continuously
monitored with a three-lead electrocardiograph, and the
mean arterial pressure was determined using sphygmo-
manometer (ALPK2, Japan) on the contralateral arm. A
rapid inflation and deflation pneumatic cuff was posi-
tioned on the imaged arm immediately proximal to the
olecranon process to provide a stimulus to forearm ische-
mia. Brachial artery diameters were analyzed at the time
of the ECG monitoring, i.e., at the beginning of QRS
complex (end diastole). The forearm cuff was then in-
flated to 200 mmHg for 5 min. Images were recorded 30
s before cuff deflation and for 2 min after deflation. Bra-
chial artery reactivity was evaluated by two-dimensional
ultrasonography (Siemens 40) with a linear, high-reso-
lution probe (10 MHz). Measurements were performed at
baseline (Figure 1) and during flow-mediated dilation
(FMD) for both patients and young healthy men. Changes
in vessel diameter were calculated for each subject as the
percentage variation of arterial diameter under different
stimuli, when compared with the baseline diameter.
Table 1. Study population.
G
1, Aerobic training (CAD) G2, Aerobic training (young men) G3, Control (CAD)
mean SD (Standard Deviation)
Age (year) 55 ± 4.33 27.7 ± 4.16 53 ± 6.43
Weight (kg) 82.1 ± 11.98 75 ± 7.84 82.85 ± 14.38
High (m) 1.73 ± 45 1.72 ± 5.51 1.741 ± 6.11

S. M. Seyediyan et al. / Health 5 (2013) 1706-1711
1708
0
1
2
3
4
5
6
7
8
9
10
Young men
Tranining Control
FMD
Figure 1. Baseline percentage of FMD in
the three groups (pretest).
2.3. Exercise Training Program
After baseline evaluation (Figure 1), the patients and
young men were randomized to receive aerobic training
(Group 1 [G1], 10 patients) (Group 2 [G2], 10 young men)
or as control not receiving the training (Group 3, [G3], 10
patients). The subjects in G1 and G2 underwent moder-
ated aerobic training thrice a week for 1 week at Tapesh
cardiac rehabilitation center. Each session included a
10-min warm up, 30 min of running on a treadmill with
telemetry monitoring and intensity set at 60% - 70% of
peak exercise heart rate measured in the second ECG
stress testing, and a 10-min cool down. G3 patients
avoided regular physical activity. Cardiac rhythm was
continuously monitored on a four-channel telemetry sys-
tem in all trained subjects (patient and young men) and
in all sessions throughout the trial. Patients and young
men in the aerobic training groups were also encouraged
to gradually increase their daily physical level.
2.4. Follow up
All tests were repeated after 2 months and the results
were compared with those of the baseline tests. The
training program in trained subjects was stopped at this
point. The arterial vasoreactivity and treadmill (Bruce pro-
tocol) tests were repeated again. Pharmacological ther-
apy remained unchanged throughout the study.
2.5. Statistical Analysis
Statistical analyses were performed with SPSS software
(version 17.0 for Windows). The data are presented as
mean ± SD. Baseline values were compared using
ANOVA and t-test to determine whether there were sig-
nificant differences among the three groups, and all the
data were analyzed from baseline to post-test using de-
pendent t-test in each group. In addition, Tukey’s post-
test, was used to study whether the magnitude of brachial
artery reactivity differed among the trained groups and
control group (young men and patients) over time (base-
line and after 8 weeks). A value of p < 0.05 was consid-
ered as statistically significant, and the authors had full
access to and take responsibility for the integrity of the
data. All the authors have and agree to the data presented
in the manuscript.
2.6. Results
None of the metabolic parameters considered was sig-
nificantly different between G1 and G3 (patients group),
but the young healthy men exhibited significant differ-
ences.
2.7. Brachial Arterial Vasoreactivity
At the initial evaluation, the baseline diameter of the
brachial artery did not differ significantly among the
three groups: 3.81 ± 0.19 SD in G1, 3.9 ± 0.41 SD in G2,
and 4.17 ± 0.76 SD in G3. In the CAD patients and
young healthy men, the basal brachial artery was not sig-
nificantly different between untrained and trained groups
(Table 2). After cuff release, we assessed FMD re-
sponses in all the groups, and the results exhibited that
the FMD responses were significantly impaired in the
CAD patients, when compared with healthy young men:
4.31 ± 1.15 SD for G1, 9.18 ± 1.45 SD for G2, and 4.64 ±
1.81 SD for G3 (Figure 2). Aerobic training significantly
increased the FMD response to forearm ischemia: (6.15
± 0.77 SD; p < 0.05) for G1, (11.72 ± 1.72 SD, p < 0.05)
for G2, and did not significantly change in the untrained
CAD patients (control group).
3. DISCUSSION
In this study, the effects of moderate aerobic training
on endothelial function through the FMD assessment are
compared with the patients with artery diseases, who had
open-heart surgery, and healthy young men with no ex-
ercise activity.
Our research has several finding as following:
Firstly, in accordance to the previous reports, endothe-
lial function can be reliably assessed by FMD in brachial
artery. However, this test was first introduced by German
scientist celermajor in which it is illustrated that FMD
reduction and brachial artery have a direct relationship
with cardiovascular diseases and risk factors or athero-
sclerosis [12]. In addition, one of the findings in the pre-
vious reports has been confirmed that the CAD patients,
who had history of myocardial infarction or Coronary
artery disease, had significantly lower FMD in com-
parison to healthy people [13]. In fact, our results are
consistent with their findings.
Secondary, regular physical activities have a strong

S. M. Seyediyan et al. / Health 5 (2013) 1706-1711 1709
Table 2. Brachial reactivity results at baseline and follow up.
G1 G
2, G3
Items
Time 0 Follow up Time 0 Follow up Time 0 Follow up
Baseline diameter, mm 3.81 ± 0.196 3.84 ± 0.202 3.9 ± 0.41 3.95 ± 0.33 4.17 ± 0.76 4.18 ± 0.73
FMD% 4.31 ± 1.15 6.15 ± *0.77 9.18 ± 1.45 11.72 ± 1.72* 4.64 ± 1.81 4.66 ± 1.30
G1: Aerobic training patients (CAD) G2: Aerobic training young men, G3: control (CAD); p < 0.05 *mean ± SD (Standard Deviation).
Figure 2. Indicated FMD% in the three groups.
positive link with vascular function by which flow blood
and shears stress would increase the vascular artery.
Moreover, it would also improve endothelium function
as it can increase the amount of NO in vascular [14].
Previous studies show that eight weeks of resistance
training in young men has caused a considerable rise in
FMD [15]. De souza did three month endurance exercise
on the youth who their Endothelium-dependent vaso-
dilatation function was increased by about 30 percent in
the year 2000 [16]. Current research on youths show that
60 to 80 percent increase in maximum heart rate after
two month aerobic exercise would lead to 21 percent
increase in FMD and finally improve endothelium func-
tion which it is in line with Thiken and Suza’s studies.
Of course the survey on stable coronary patients shows
that after eight weeks aerobic and resistance exercises ,a
rise and an improvement on FMD and vascular endothe-
lial-dependent vasodilatation function respectively. Fur-
thermore, Hambrekht executed four weeks aerobic exer-
cises on CAD patients [7] and Vona and his colleagues
performed different types of exercises such as aerobic
and resistance ones on patients who recently had a myo-
cardial infraction [17]. All findings lead to an improve-
ment on the evaluation of coronary endothelial function
via FMD assessment which they were in line with sub-
ject of current research on interventional treatment like
angiography and open heart surgery. Contrary, but Jodin
and his colleagues after three month exercise on CAD
patients could not achieve acceptable result and the FMD
was not altered [18].
Third, endothelium dysfunction deficiency is one of
major dangerous factors in cardiovascular diseases which
through brachial artery FMD measurement or high qua-
lity sonography as alternative to Non-invasive detection
of atherosclerosis patients are used. However, it is con-
sidered as easy method to evaluate coronary endothelial
function in children and siblings in order to predict and
prevent early vascular structural changes [19].
Fourthly, comparison of FMD percentage in both
groups, young men and coronary patients, were predict-
able. However, FMD alterations in CAD patients (con-
trol group), three month after drug treatment and diet,
remained down and after 8 weeks too lowly. Our results
agree with medical therapy (statin) after 10 weeks faield
to improve endothelium-dependent function in CAD pa-
tients [20] but it is unconvienced with Ling and et al.,
short term simvastatin therapy increases endothelial
function in patients with stable CAD [21]. Furthermore,
the exercises considers as method of intervention in car-
diac rehabilitation and vascular disease.
Finally, it was described that the major objectives of
cardiac rehabilitation centre and sports medicine are as
follows:
● decrease the number of deaths and its complications;
● life style improvement;
● prevent their return to health clinics and early pre-
vention and prediction of groups at risk.
4. LIMITATIONS OF STUDY
During the study, there were some restrictions which
we attempted to solve them.
The number of people who were interested in research
involvement was reduced by prolongation of the project.
Additionally, scholar’s movement between these two
clinics (Cardiac rehabilitation clinic and Sports medicine
clinic) caused to increase expenses, project time and lack
of coordination. Finally, some of patients were suffered
from disability and orthopedic disability which they were
removed from the list and replace them with the other
candidates.

S. M. Seyediyan et al. / Health 5 (2013) 1706-1711
1710
5. CONCLUSION
The present study demonstrates endothelial dysfunc-
tion persisting in CAD patients that were revascularized
and aerobic exercise can improve vascular endothelial
function in CAD patients and healthy young men.
6. ACKNOWLEDGEMENTS
The research is taken from the thesis of Dr Hamidian and Dr Haji-
zadeh and the financial and educational supports were received from
the heart and vascular center of university of medical sciences of Joun-
diShapour University and physical education department of Azad Uni-
versity of Shushter Branch.
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