Koncor1_2014.PM6


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IJMMR 2015 Vol. 1 No. 1

INSTRUMENTAL AND DIAGNOSTIC CRITERIA OF HEMODYNAMIC
DISORDERS AND ENDOTHELIAL DYSFUNCTION CORRECTION
IN PREGNANTS WITH ARTERIAL HYPERTENSION

S. M. Heryak, I. Ye. Humenna
I. YA. HORBACHEVSKY TERNOPIL STATE MEDICAL UNIVERSITY, TERNOPIL, UKRAINE

Background. According to the WHO, hypertension is associated with 20-33 % of maternal death during
pregnancy within extragenital pathology statistics. There are complications of the fetus and newborn associated
with hypertension at 140/90 mm Hg and higher.

Objective. A comparative analysis of antihypertensive therapy effectiveness in pregnants with arterial
hypertension was performed using modern clinical and instrumental methods of endothelial function diagnostic,
central and utero-placental hemodynamic estimation.

Methods. We examined 63 pregnant women with hypertension at 28 to 32 weeks of gestation. Women
were randomized into three groups:group I (control group – 20 women), that included pregnant women with
hypertension treated with basic antihypertensive therapy as recommended by Health Ministry of Ukraine
standards (metildofa and nifedipin); group II – 21 pregnant women receiving metildofa and metoprolol; group III
(22 pregnant women) receiving metildofa and nebivolol.

Conclusions. It was found that the brachial artery ultrasound measuring and occlusive plethysmography
procedure by Dietz is an early and safe method of endothelial dysfunction diagnostic in pregnants with
hypertension. Doppler ultrasound of blood flow in uterine, umbilical arteries, and middle cerebral arteries of the
fetus allows timely diagnosis of the side effect of antihypertensive drugs on the fetus. The therapy of choice for
pregnants with Stage II Arterial Hypertension should be based on methyldopa and calcium channel antagonists
or selective beta-blockers combination. Highly selective beta-blockers with vasodilative effect (nebivolol
hydrochloride) and L-arginine (Tivortin) allow to prevent perinatal adverse effects of antihypertensive therapy,
to correct hemodynamic disorders and endothelial dysfunction in pregnants with arterial hypertension.

KEY WORDS: arterial hypertension, uterine-placental hemodynamics, endothelial dysfunction.

Introduction
According to the WHO, hypertension is asso-

ciated with 20-33 % of maternal death during
pregnancy within extragenital pathology statistic.
There are complications of the fetus and newborn
associated with hypertension at 140/90 mm Hg and
higher [1, 5, 7]. Mechanisms of increased blood
pressure, leading to hypertension and/or
strengthening of symptoms during pregnancy are
very diverse. A major role of endothelial dysfunction
(ED) in the development of hypertension is shown
in the recent years. It is characterized by reduced
synthesis of nitric oxide as one of the main
vasodilators [3, 8, 9]. Unfortunately, ongoing
antihypertensive therapy does not improve
pregnancy outcomes for the fetus, and even lead to
higher frequency of low weight for gestational age
newborns. Overall, high blood pressure decreases
due to drug therapy and may improve pregnancy

outcomes for the mother but not for the fetus [4, 6,
11]. Antihypertensive drug therapy choice during
pregnancy is metyldophamine as it was proved to
be safe for the fetus. The second-line drugs include
calcium channel blockers. They are recommended
for the treatment of high arterial blood pressure in
pregnant females when refractory hypertension to
methyldopa therapy occurs [2, 12]. The antihyper-
tensive drugs of the second line for pregnant women
also include �-blockers, but their use is limited due
to the development of adverse effects to the fetus
[1, 2, 10]. It is necessary to choose an optimal set of
long-term antihypertensive treatment for pregnant
women which will not have a negative effect on the
fetus. That is why it is very important to perform
detailed comparative analysis of differential
approaches to the treatment of hypertension during
pregnancy and perinatal complications.

The aim is to investigate endothelial dysfunction
in pregnants with hypertension using non-invasive
instrumental methods and offer an optimal therapy
program for pregnants with arterial hypertension and

Address for correspondence: S.M. Heryak, Medical
Biochemistry Department,  m. Voli, 1, Ternopil, 46001,
Ukraine
Tel.: +380 352254891

S. M. Heryak et al.

International Journal of Medicine and Medical Research
2015, Volume 1, Number 1, p. 30-34
copyright © 2015, TSMU, All Rights Reserved



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IJMMR 2015 Vol. 1 No. 1

to minimize the negative impact of the antihypert-
ensive drugs on fetus.

Methods
We examined 63 pregnant women with hyper-

tension at 28 to 32 weeks of gestation, which were
hospitalized to the Ternopil Regional Perinatal Center
“Mother and Child” of the Department of extrage-
nital pathology for pregnant.

Clinical research was performed for all pregnant
women according to the Ministry of Health of Ukraine
standards: clinical analysis of blood and urine,
biochemical blood analysis, assessment of urinary
albumin excretion to detect microalbuminuria, as well
as ECG, echocardiography, ultrasound investigation
of renal and peripheral vessels.

We used modified technique by Dietz N. M.
(1996) [6, 10], based on the measurement of the
diameter of the vessel (by ultrasound) and peripheral
vascular resistance (occlusal plethysmography), in
order to assess endothelial function and its effect on
uteroplacental hemodynamic.

Initially, the brachial artery diameter (distance
between opposite walls of the artery) was measured
in systole phase via linear 7 MHz sensor. Then
arterial blood pressure was measured with classic
manual tonometer. The pressure, equal to systolic
plus 50 mm Hg, was injected into the cuff for 5
minutes. Measuring of the artery diameter was
carried out immediately and again after 10 minutes.

Cardiotocography (CTG) with a score on a
Fisher’ scale and biophysical profile were used to
assess the functional status of the fetus. The deve-
lopment of the fetus was evaluated by comparing
ultrasonic fetometry under percentile tables in
dynamic survey of 4 weeks after the previous test.
Blood flow was assessed at uterine arteries, umbilical
arteries, and middle cerebral arteries of the fetus
with ultrasonic Doppler.

Women were randomized into three groups:
group I (control group – 20 women), which included
pregnant women with hypertension treated with basic
antihypertensive therapy as recommended by MOH
Ukraine standards (metildofa and nifedipin); group

II – 21 pregnant women receiving metildofa and
metoprolol;group III (22 pregnant women) receiving
metildofa and nebivolol. Pregnants of all three groups
were treated orally with low-dose aspirin, calcium
supplements, and magnesium for the prevention of
preeclampsia according to the Ministry of Health of
Ukraine standards.

Statistical analysis: data analysis was done and
verified using Statsoft STATISTICA 10 at Systemic
Statistical Analysis Department of Ternopil State
Medical University.

Results
Basic antihypertensive therapy for all groups

included dopegit four times a day. Women of the
Group I were treated with nifedipin 20 mg per day
in four divided doses to stabilize blood pressure.
Pregnants of the Group II were treated with
metoprolol at a dose of 25 mg per day in two
divided doses. Pregnant women of the Group III
were prescribed nebivolol hydrochloride 5 mg
once a day as a highly selective third generation
beta blocker with vasodilative properties and ability
to modulate the synthesis of the nitric oxide by
the blood vessels endothelium. The endothelial
dysfunction treatment should be considered as a
strategic line for effective prevention of
cardiovascular complications of the arterial
hypertension as pregnancy treatment. Therefore,
women of the second and the third groups were
administered L-arginine aspartate (Tivortin) 1 g
(5 ml) orally six times per day for 14 days in
addition to antihypertensive preparations.

The gestational term of 28-32 weeks and arterial
hypertension stage II were the criterions for rando-
mization. Study groups were homogeneous for age,
obstetric history, and the course of the underlying
disease. Exclusion criteria were defined as following:
hypertension stage III, severe concomitant extra-
genital pathology (diabetes, diseases of the thyroid
gland, other cardiovascular pathology).

We observed different hemodynamic norma-
lization and stability of blood pressure after treat-
ment in each group (Table 1).

Table 1. Blood pressure and heart rate in women of the surveyed groups during
dynamic treatment (M±m)

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Note: p<0.01 – data accuracy.

S. M. Heryak et al.



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IJMMR 2015 Vol. 1 No. 1

Pregnant women of the Group I showed poor
tolerability to the therapy. Particularly, we observed
sudden changes in blood pressure (hypotension epi-
sodes below 100/60 mm Hg or hypertensive crises
(blood pressure above 160/110 mm Hg) in three pre-
gnant women; four pregnant women developed swel-
ling and redness of the face, seven women com-
plained about palpitations, dizziness and weakness.

Simultaneously, eight patients of the second
group experienced bradycardia (less than 60 bpm),
while another five complained about dyssomnia,
dizziness, weakness, and increased edema.

The best tolerability to the therapy was observed
in the third group, where only two pregnant women
noted weakness and headache while the heart rate
slowed down below 60 bpm in two women. Also, as
it is shown in Table 1, the clinically most effective
scheme of arterial pressure normalization was the
combination of nebivolol hydrochloride and metildofa
on the background intake of L-arginine.

Forty four (70.9 %) of the surveyed women
experienced ECG changes before treatment: the
deviation of the electrical axis of the heart to the left,
ST segment depression, inversions or flattening of
T wave in leads II, III and avF. In pregnants of the
Group I tachyarrhythmia was observed, including
seven women (36.8 %) with arrhythmias. Brady-
arhythmia and conduction disturbances (different
degrees of blockages) were observed in nine
pregnants of the Group II (42.9 %). Conduction dis-
orders and slowing heart rate were observed in six
women of the third group (27.2 %).

As for results of the sonogram of the heart,
ejection fraction in all three groups before treatment
was 63.3 %±3.4 %, and it decreased insignificantly

after the treatment only in the second group. All
females in all three groups (38 females, 62.1 %) were
equally affected by end-diastolic increase in the size
of the right ventricle, and an increase of the index of
left ventricular mass by 10–15 %. Ten pregnant
women (16.1 %) showed increase of the index of
the left ventricular mass from 15.1 to 27.8 %, which
may be classified as excessive. Combined
preeclampsia developed in seven females (two
pregnants from the first group, three from the second
group, and two from the third group).

Data for the indicators of the endothelial function
are presented in Table 2.

In all three groups, the diameter of the brachial
artery before treatment should be assessed as
narrowed. Therefore, an endothelial dysfunction is
observed in pregnants with hypertension, which is
manifested by spasm of the arteries. There was a
significant dilatation of the brachial artery with slow
normalization of arterial tonicity for the Group I after
the treatment (diameter 4.4 mm±0.2 mm and
endothelium-dependent dilatation was more than
22 %, which is relatively higher than in healthy
pregnant women). Pregnants of the second group
experienced spasm of the arteries, and this condition
did not normalize. As for the third group, the diameter
of the brachial artery was significantly restored to
the values close to the healthy pregnant women and
endothelium-dependent vasodilation (18.4 %)
showed a normal tone of arteries and their ability to
respond adequately to stimulation. Therefore, the
endothelial function was restored in the Group III of
patients to the highest level.

We have also established a relationship between
fetometric performance relative to the gestational

Table 2. Indicators of the endothelial function (M±m)

Note: p<0.01 – data accuracy.

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Table 3. The main parameters of fetometry during treatment of pregnants with hypertension
of 32–34 weeks term (M±m)

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S. M. Heryak et al.



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IJMMR 2015 Vol. 1 No. 1

term and the option of antihypertensive therapy on
the basis of surveys (Table 3).

The size and weight of the fetus is less than
average in the general population according to the
gestational age in women with hypertension, which
is often due to the disruption of hemodynamics in
the mother-placenta-fetus system. Therefore, accor-
ding to the ultrasound examination of the surveyed
patients, the average biparietal diameter decreased
for a given gestational age and evidence about
disruption of uteroplacental hemodynamics; more-
vover, after the treatment, biparietal diameter was
the biggest in the third group, followed by the first
group and the second group. As for indicative para-
meters such as average diameter of the abdomen
and femur length, best values were observed in the
third group that explains normal fetal fatness and
skeleton development, and therefore the optimal
normalization of utero-placental hemodynamics,
which correlated with indicators of endothelial
function. Thus, the maximum normalization of the
biometric parameters was observed in the third group
of pregnant women.

Doppler velocimetry is helpful to evaluate blood
circulation in the placenta and detect early signs of

poor circulation. To assess the blood circulation, the
following indices are used: systolic-diastolic ratio
(SDR), pulsation index (PI) and index of resistance
(IR), all of those are shown in Table 4.

The degree of hemodynamic disorders in the
mother-placenta-fetus system is evaluated according
to the Medvedev classification: 1A – isolated viola-
tions of the utero-placental blood flow; 1B – isolated
violations of the feto-placental circulation; II – violation
of utero- placental and feto-placental circulation does
not reach the critical meanings; III – decompensated
disorders and circulatory centralization.

Based on our results, we can conclude that
pregnant women of the Group I experienced slight
improvement of the parameters of the uterine artery
blood flow, but no significant improvement of blood
flow in the umbilical artery and middle cerebral artery
of the fetus. Pregnant women of the second group
showed insignificant worsening of the blood flow in
the uterine arteries, umbilical artery and middle
cerebral artery. Pregnant women of the third group
were characterized by a slight improvement in blood
flow of the uterine artery and nonsignificant impro-
vement in umbilical artery and middle cerebral artery
of the fetus.

Note: p<0.01 – statistical significance and data accuracy.

Discussion
Summing up the results of the abovementioned

surveys, we can assume that in order to minimize
side effects during gestation, the cardioselective
�-blockers with vasodilation properties should be
preferred. These drugs will prevent the increase in
total peripheral vascular resistance and can smooth
the negative effects of classical beta blockers
(delayed intrauterine development, bradycardia,
hypotension, hypoglycemia, respiratory depression
of the fetus).

Conclusions
1. It was found that the brachial artery ultrasound

measuring and occlusive plethysmography proce-
dure by Dietz is an early and safe method of endo-

Table 4. Doppler velocimetry in surveyed groups of pregnant women after 30 weeks of gestation

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thelial dysfunction diagnostic in pregnants with
hypertension. Doppler ultrasound of blood flow in
uterine arteries, umbilical arteries and middle
cerebral arteries of the fetus allows timely to reveal
the side effect of antihypertensive drugs on the fetus.

2. The therapy of choice for pregnants with
Stage II Arterial Hypertension should be based on
methyldopa and calcium channel antagonists or
selective beta-blockers combination.

3. Highly selective beta-blockers with vaso-
dilative effect (nebivolol hydrochloride) and L-arginine
(Tivortin) let us to prevent perinatal adverse effects
of antihypertensive therapy, to correct hemodynamic
disorders and endothelial dysfunction in pregnants
with arterial hypertension.

S. M. Heryak et al.



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References
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Received: 2014.06.02

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