CARDIOVASCULAR JOURNAL OF AFRICA • Vol 24, No 9/10, October/November 2013
AFRICA
357
There were significantly negative correlations between the
TIMI frame count and plasma levels of eNOS at baseline
and after exercise (
r
=
–0.51,
p
=
0.015,
r
=
–0.58,
p
=
0.005, respectively) (Figs 2, 3). Moreover, there was a positive
correlation between the rate–pressure product and plasma levels
of eNOS after exercise in patients with SCF (
r
=
0.494,
p
=
0.019) (Fig. 4).
Discussion
The main objective of our study was to assess plasma eNOS
levels and their response to exercise in patients with SCF. The
main findings of our study were: (1) plasma levels of eNOS were
lower in SCF patients than in control subjects, (2) the differences
in eNOS levels between the two groups became greater after
the exercise treadmill test, as a result of a significant decrease
in plasma eNOS levels in patients with SCF, (3) there were
significantly negative correlations between TIMI frame count
and plasma levels of eNOS at baseline and after exercise, and
(4) there was a positive correlation between the rate–pressure
product and plasma levels of eNOS after exercise in SCF patients.
SCF is a pathology that causes typical angina pectoris and
decreases the flow velocity of contrast agents in the coronary
arteries of patients with normal coronary angiography.
1
Despite
well-defined angiographic characteristics of SCF, knowledge on
its clinical significance and aetiopathogenesis are insufficient.
Occlusive disease of the small vessels, microvascular and/
or endothelial dysfunction have been over-emphasised in the
aetiology of this disease. It was shown in previous studies that
the pathophysiology of SCF was at the microvascular level and
the disease has a dynamic character.
1,2,14
A microcirculatory
disorder of SCF was also clearly demonstrated in the results of
these studies.
3,15
The effects of exercise on the coronary microvascular tone are
controversial. Sympathetic activation increases coronary flow,
with both increasing heart rate and myocardial contractility,
16
and endothelium-mediated vasodilation.
17
Besides, increased
sympathetic stimulation may also cause abnormal microvascular
constriction in endothelial dysfunction.
18
Essentially, the net
effect of exercise is related to the pathophysiological state of the
small coronary arteries.
The endothelium normally displays a vasodilatory feature
against various systemic, neurohumoral and mechanical stimuli,
and regulates vasomotor tension, thrombosis, fibrinolysis,
vascular cell growth, and leukocyte and platelet adhesion by
secreting growth factors and inhibitors such as NO.
19
NO is a
key molecule in normal autoregulatory mechanisms such as
Fig. 1. Plasma eNOS levels at baseline and after exercise
in the study population.
50
45
40
35
30
25
20
15
10
5
0
SCF
Control
Endothelial nitric oxide
synthase levels (pg/ml)
p
<
0.001
p
=
0.35
Basal
After exertion
TABLE 1. CLINICAL CHARACTERISTICS OF
PATIENTAND CONTROL GROUPS
Clinical characteristics
SCF (
n
=
22)
Control (
n
=
17)
p
-value
Age (year)
48.5
±
10.9
48.7
±
9.6
NS
Male gender,
n
(%)
19 (86.4)
12 (70.6)
NS
BMI (kg/m
2
)
23.4
±
1.7
23.2
±
1.6
NS
Systolic blood pressure (mmHg)
116.5
±
7.2
117.0
±
6.8
NS
Diastolic blood pressure (mmHg)
76.2
±
4.9
73.4
±
5.2
NS
Smoking,
n
(%)
14 (63.6)
11 (58.8)
NS
Family history,
n
(%)
13 (54.2)
9 (60.0)
NS
Fasting blood glucose (mg/dl)
87.0
±
7.5
87.3
±
9.2
NS
Total cholesterol (mg/dl)
174.1
±
24.1
180.6
±
30.0
NS
LDL cholesterol (mg/dl)
117.8
±
36.8
121.0
±
31.7
NS
HDL cholesterol (mg/dl)
40.8
±
8.4
36.3
±
8.0
NS
Triglyceride (mg/dl)
99.0
±
27.6
111.5
±
31.5
NS
Ejection fraction (%)
61.1
±
3.8
61.1
±
3.9
NS
TIMI frame count
49.4
±
11.7
19.9
±
5.9
<
0.001
SCF: slow coronary flow, LDL: low-density lipoprotein, HDL: high-density lipopro-
tein, TIMI: thrombolysis in myocardial infarction, NS: not significant.
TABLE 2. EXERCISE PARAMETERS OF STUDY POPULATION
Exercise parameters
Controls (
n
=
17) SCF (
n
=
22)
p
-value
Baseline heart rate (bpm)
70.1
±
2.8
69.0
±
3.6
NS
Peak exercise heart rate (bpm)
185.9
±
10.8 159.5
±
10.3
<
0.001
Peak systolic blood pressure (mmHg)
193.6
±
10.8
179.9
±
9.3
<
0.001
Baseline rate–pressure product
81.6
±
5.6
80.6
±
5.3
NS
Peak exercise rate–pressure product
360.3
±
32.4 287.2
±
26.5
<
0.001
Angina,
n
(%)
–
4 (18)
−
ST segment depression,
n
(%)
–
7 (32)
–
Both angina and ST depression,
n
(%)
–
3 (14)
–
SCF: slow coronary flow, NS: not significant.
TABLE 3. BASALAND POST-EXERTION PLASMA BNP,
CRPAND ENOS LEVELS
eNOS (pg/ml)*
SCF (
n
=
22)
Control (
n
=
17)
p
-value
Basal
32.58
±
21.36
48.16
±
24.35
0.040
Post-exertion
25.02
±
17.69
44.13
±
17.39
0.002
SCF: slow coronary flow, eNOS: endothelial nitric oxide synthase, NS: not significant.
*
p
<
0.001 (baseline and after exercise in patients with SCF).
Fig. 2. Relationship between TIMI frame count and plas-
ma levels of eNOS at baseline.
100.00
80.00
60.00
40.00
20.00
0.00
30.00
40.00 50.00 60.00 70.00
TIMI frame count
Plasma levels of eNOS
at baseline (pg/ml)
r
=
–0.51,
p
=
0.015