Download Effect of Atenolol on Left Ventricular Function in

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Clinical Science (1980)5 9 , 4 7 3 ~ 4 7 5 s
Effect of atenolol on left ventricular function in hypertensive
patients
M. M O H S E N I B R A H I M , M. A Z I Z M A D K O U R A N D R A G A A M O S S A L L A M
The Cardiac Department and the Technology Transfer Focus,Cairo University and General Public Transport Hospital, Cairo,
Egypt
Summary
1. Atenolol (100 mg/day) was given to 12
hypertensive patients for 8 weeks, and its effects
on mean arterial pressure, cardiac index and
ejection
phase
indices
of
myocardial
performance
were examined by echocardiography.
2. Echocardiographic studies were made
before treatment after 4 weeks on placebo and
repeated after 4 and 8 weeks of atenolol therapy.
Mean arterial pressure fell by 14 and 21% after 4
and 8 weeks respectively. Cardiac index fell by 22
and 20%, and stroke index fell by 11 and 7%.
Calculated peripheral resistance did not change
significantly.
3. Ejection phase indices, namely fractional
shortening, ejection fraction and normalized
mean rate of circumferential fibre shortening, did
not change. End-diastolic volume index did not
change and there was no relationship between
changes in heart rate and end-diastolic volume
index.
4. The study shows that atenolol in the resting
state has no effect on certain echocardiographic
indices of left ventricular function when given
orally to hypertensive patients with normal left
ventricular size and function. The reduction in
cardiac and stroke indices were presumably
secondary to a decrease in cardiac venous filling.
Key
words:
atenolol,
cardiac output,
contractility, echocardiography, left ventricle.
Introduction
Atenolol is a /3-adrenoreceptor-blocking drug
with cardio-selective properties, which is effective
in the treatment of hypertension (Myers, Lewis,
Correspondence: Dr. M. Mohsen Ibrahim, 1,
El-Sherifein Street, Cairo, Egypt.
Steiner & Dollery, 1976). In acute and long-term
haemodynamic studies the drug produced a
marked reduction in cardiac output with variable
but generally little effect on calculated total
peripheral resistance (Lund-Johansen, 1976).
Studies in animals have show that atenolol has no
negative inotropic effect (Harry, Knapp &
Linden, 1974). However, the effects of atenolol
on myocardial contractility have been
demonstrated less frequently in man and then
only in acute intravenous experiments (Robinson,
Jackson, Fisk & Jewitt, 1978). Information
regarding its effect on left ventricular function
after oral therapy have not been reported.
The purpose of this work was to study the
effects of oral atenolol therapy on arterial
pressure, cardiac output and left ventricular
contractile state in hypertensive patients.
Methods
Twelve male subjects with essential hypertension
were studied as outpatients. Secondary
hypertension was excluded as described
previously (Ibrahim & Mossallam, 1978).
Each patient was followed initially for 4 weeks,
during which all previous antihypertensive
medication was discontinued and placebo was
given. Blood pressure and heart rate were
checked at twice-weekly intervals in the supine
and standing positions. If at the end of this 4
week placebo pretreatment period supine
diastolic blood pressure was greater than 95
mmHg, the patient was included in the study.
This then comprised a further 4-8 week
treatment period during which all patients were
started with a dose of 100 mg of atenolol once
daily.
At the conclusion of the 4 week pretreatment
(first placebo) period, each patient underwent
echocardiographic evaluation (Ibrahim, 1979).
'
M . Mohsen Ibrahim, M . Aziz Madkour and Ragaa Mossallam
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The left ventricular ejection time (LVET) was
measured from a simultaneously recorded
external carotid arterial pulse tracing.
Left ventricular volumes were derived by
cubing end-diastolic diameter (EDD) and endsystolic diameter (ESD). The difference between
the end-diastolic volume (EDV) and end-systolic
volume (ESV) was the left ventricular stroke
volume. Cardiac output was derived by
multiplying the heart rate in the simultaneous
electrocardiographic record by the stroke
volume.
The ejection fraction (EF) was derived from
(EDV - ESV)/EDV. The fractional shortening
(FS) was calculated as (EDD - ESD)/EDD.
The normalized mean rate of circumferential
fibre shortening (circ./s) was calculated as (EDD
- ESD)/(LVET x EDD).
Blood pressure was recorded immediately
before each study with a standard sphygomomanometer. The mean arterial pressure was
calculated by adding one-third the pulse pressure
to the diastolic blood pressure (phase 5).
Corrections were made to account for changes
in body surface area and the cardiac index, stroke
index and the end-diastolic volume index were
obtained by dividing the cardiac output, stroke
volume and end-diastolic volume by the body
surface area respectively. The cardiac index and
calculated mean blood pressure were used to
estimate the total peripheral resistance.
Total peripheral resistance (units m2) =
mean arterial presure/cardiac index
Echocardiographic studies were repeated in all
patients at the conclusion of 4 weeks of atenolol
treatment and again after 8 weeks in eight
patients.
0.01).
The pretreatment stroke index was 66 4.87
ml/m2. After 4 weeks of therapy there was an
average decrease by 7-3 ml/m2 (1 1%) and after 8
weeks by 4.5 ml (7%). There was a significant
correlation between changes in stroke index and
changes in circumferential fibre shortening ( r =
0.694, P < 0.01).
The pretreatment total peripheral resistance
index was 33 + 2.87 units/m2. The total
peripheral resistance index increased after 4
weeks of therapy by 4.08 2.16 units/m2 (12%).
After 8 weeks it decreased by 1.13 t 3.25
units/m2 (3%).
*
End-diastolic volume index
The pretreatment end-diastolic volume index
was 93 5-9 ml/m2. At the conclusion of 4 and
8 weeks treatment the changes in end-diastolic
volume index were insignificant and inconsistent.
There was no relationship between changes in
heart rate and end-diastolic volume index.
*
Fractional shortening, ejection fraction and
normalized mean rate or circumferential fibre
shortening
Changes in fractional shortening were
insignificant after either 4 or 8 weeks of therapy.
The pretreatment fractional shortening was 34.9
2.16%. After atenolol treatment fractional
shortening was 33.8 1.66 and 35.3 2.74%.
Similarly ejection fraction did not change after
atenolol treatment.
Changes in circumferential fibre shortening
after atenolol therapy were insignificant. The
pretreatment values ranged between 0.52 and
1.60 circ./s (1-13 0.088 circ./s). After 4 and 8
weeks of atenolol circumferential fibre shortening was 1-05 0.078 and 1.19 & 0.14 circ./s
respectively.
*
Results
Arterial pressure and heart rate
The mean arterial pressure was reduced in all
4.79 to
subjects by 10% or more, from 141
121 4.72 mmHg after 4 weeks and to 114
6-23 mmHg after 8 weeks of atenolol therapy.
Cardiac rate decreased in all patients from 7 1
2.58 to 63 t 2.54 beatdmin and to 61 & 3-31
beats/min after 4 and 8 weeks respectively.
*
normal subjects for our laboratory is 3.56-5.47 1
min-' m-z with echocardiographic methods.)
After 4 weeks of atenolol treatment cardiac index
fell to 3.57 0.30 I min-I m-Z. At week 8 it
reached 3.30 0.21 1 min-' m-2. There was no
relationship between changes in cardiac index
and changes in mean arterial pressure, but the
changes were significantly related to changes in
circumferential fibre shortening ( r = 0.726, P <
*
*
*
*
*
*
Cardiac index, stroke index and total peripheral
resistance
Discussion
The pretreatment cardiac index ranged
between 3.15 and 5.95 I min-' m-2 (4-58 0.28
1 min-' m-2). (The range of cardiac index in
The use of ejection-phase indices of myocardial
performance in our study was based upon data
from previous observations. A linear correlation
*
Atenolol and heart in hypertension
was found between echocardiographic ejectionphase indices, fractional shortening, ejection
fraction, normalized mean rate of circumferential fibre shortening and similar angiographic measurements (Cooper, O'Rouke,
Karliner, Peterson & Leopold, 1972). Furthermore, ejection-phase contractile indices have
previously been shown to provide a practical and
physiologically reasonable means of assessing the
level of basal myocardial contractile state
(Peterson, Skloven, Ludbrook, Uther & Ross,
1974).
The present study supports the previously
reported effectiveness of atenolol in lowering high
blood pressure (Myers et al., 1976). The fall in
blood pressure was secondary to a reduction in
cardiac index, the effect on calculated total
peripheral resistance was variable and insignificant. On the other hand, there was no correlation
between the fall in mean arterial pressure and the
reduction in cardiac index; thus the changes in
blood pressure and those in cardiac index
occurred independently.
The reduction in cardiac index was due to both
cardiac slowing and decrease in stroke index. The
changes in heart rate and stroke index were only
significant after 8 weeks of therapy.
Atenolol produced no significant change in
the ejection-phase indices of myocardial
performance, namely fractional shortening,
ejection, fraction and circumferential fibre
shortening. Studies in animals have shown that
atenolol has no negative inotropic effect (Harry
et al., 1974).
The end-diastolic volume index did not change
after atenolol treatment in spite of cardiac
slowing. Recent investigations (De Maria,
Newmann, Schubart, Lee & Mason, 1979)
showed that in normal persons cardiac
acceleration produces a reduction in cardiac
dimensions and increase in circumferential fibre
shortening and that cardiac size was significantly
affected by alterations in heart rate. In our study
we found no relationship between end-diastolic
volume index and heart rate. To explain these
discrepancies atenolol may reduce cardiac
venous filling and thus end-diastolic volume index
would not increase with cardiac slowing. This
assumption can also explain the reduction in
stroke index after atenolol therapy. Our studies
demonstrate that atenolol given orally does not
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depress cardiac contractility. Reduction in stroke
index must be due to mechanisms other than
simple depression of cardiac function. It is
possible that atenolol, like propranolol (Tarazi,
Frohlich & Dustan, 1971), produces contraction
of blood volume. Either this factor alone or a
redistribution of intravascular volume away from
the heart (secondary to an increase in venous
distensibility) that favours a diminution in venous
return is responsible for the fall in stroke index. A
decrease in venous tone after Padrenoreceptor
blockade with pindolol has been reported in
hypertensive patients (Atterhog, Duner &
Pernow, 1976).
Acknowledgment
This work was supported in part by N.S.F. grant
no. OIP76-10455.
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