Download Serial changes in pulmonary haemodynamics

Clinical Science (1991)80,113-1 17
113
Serial changes in pulmonary haemodynamics during human
pregnancy: a non-invasive study using Doppler
echocardiography
STEPHEN C. ROBSON*, STEWART HUNTERt, RICHARD J. BOYS$
AND
WILLIAM DUNLOP*
Departments of *Obstetrics, TPaediatric Cardiology and $Statistics, University of Newcastle Upon Tyne, Newcastle upon Tyne, U.K.
(Received 24 April/24 July 1990; accepted 21 August 1990)
SUMMARY
1. Serial pulmonary haemodynamic investigations
were performed in 1 3 women before conception, at
monthly intervals throughout pregnancy, and then at 6
months after delivery.
2. Mean pulmonary artery pressure was calculated
from pulsed Doppler pulmonary velocities. Pulmonary
flow was measured by Doppler and cross-sectional echocardiography. These two measurements were used to calculate pulmonary vascular resistance.
3. Mean non-pregnant pulmonary artery pressure was
13.8 mmHg and no significant change was demonstrated
during pregnancy.
4. Pulmonary flow increased from 4.88 to 7.19 litres/
min during pregnancy.
5. Pulmonary vascular resistance decreased from 2.85
resistance units before pregnancy to 2.17 resistance units
at 8 weeks gestation. Thereafter there was no further significant change, values returning to pre-pregnant levels by
6 months after delivery.
Key words: echocardiography, pregnancy, pulmonary
haemodynamics.
Abbreviations: AT, acceleration time; CO, cardiac output;
ET, ejection time; MPAP, mean pulmonary artery pressure; RU, resistance units; TPR, total peripheral resistance.
INTRODUCTION
Systemic blood pressure falls during early pregnancy,
reaching a nadir during the second trimester, and then
Correspondence: Professor W. Dunlop, Department of
Obstetrics, University of Newcastle Upon Tyne, Princess Mary
Maternity Hospital, Great North Road, Newcastle Upon Tyne
NE2 3BD, U.K.
rises to non-pregnant levels or higher by term [ l , 21.
Cardiac output (CO),measured in the left lateral position,
increases during the first half of pregnancy and thereafter
probably remains fairly constant [3, 41, although some
workers have reported a small terminal fall [5]. These
changes would suggest that systemic vascular resistance
falls dramatically during the first half of pregnancy and
then may rise slightly towards term [4]. In contrast to the
changes in the systemic circulation, little is known about
the pulmonary circulation during normal pregnancy.
Right heart catheterization studies, in small numbers of
normal subjects, have suggested that mean pulmonary
arterial pressure (MPAP) does not change during pregnancy [6-81. No study has reported serial pulmonary
haemodynamic measurements during pregnancy and in
view of the small but definite risk of right heart catheterization [9], such a study is unlikely to be performed.
Pulmonary blood flow velocities, recorded using
pulsed Doppler echocardiography, have recently been
used to study pulmonary haemodynamics. The ratio
between pulmonary artery acceleration time (AT) and
right ventricular ejection time (ET) has been reported to
correlate closely with systolic pressure or MPAP in adults
[ 10- 121. Combination of velocity measurements with
cross-sectional area measurements also allows calculation
of pulmonary flow [13, 141. Thus an index of pulmonary
vascular resistance can be calculated from non-invasive
measurements of pressure and flow [ l l , 151. We have
used these techniques to study serially changes in pulmonary arterial pressure and resistance throughout pregnancy.
METHODS
Subjects and methods
Thirteen healthy young women with regular menstrual
cycles were studied. The subjects were recruited before
114
S. C. Robson et al.
Fig. 1. Doppler velocity trace from the main pulmonary artery. The velocity integral is indicated
by the cross-hatched area.
conception as part of a longitudinal study of CO during
pregnancy. None of the women had used a hormonal
method of contraception for at least 2 months and none
smoked. The details of these subjects and the changes in
CO, measured at the aortic, pulmonary and mitral valves,
have been reported previously [4].The experimental protocol was approved by the Ethical Committee of Newcastle Health Authority. Informed consent was obtained
from each subject.
Investigations were performed on day 21 of two consecutive menstrual cycles and the mean was used as a
non-pregnant control value for future comparison. The
subjects were asked to provide a specimen of urine for
human chorionic gonadotrophin estimation ( p Stat;
Alpha Laboratories) if their menstrual periods were
delayed for 3 days. Investigations were repeated as soon
as possible after conception was confirmed (mean 35
(range 31-40 days) after the last menstrual period) and
then at monthly intervals from 8 weeks to 36 weeks of
pregnancy with a final investigation at 38 weeks. Ultrasonic measurement of biparietal diameter at 16-18 weeks
of pregnancy confirmed the menstrual dates in all cases.
Final investigations were performed 6 months after
delivery.
Subjects were studied between 09.00 and 17.00 hours
having been asked to refrain from eating for 4 h before
attendance. All investigations were performed in the left
semi-lateral position using a cross-sectional phased-array
echocardiographic Doppler system (Hewlett-Packard
77020A). Pulmonary velocities were recorded using
pulsed Doppler in the parasternal short axis plane, with
the sample volume placed in the centre of the pulmonary
artery just distal to the pulmonary valve. Pulmonary velocities together with an electrocardiograph were recorded
on a strip chart at a paper speed of 100 mm/s. AT was
measured from the onset of flow to the point of peak flow
velocities and right ventricular ET was measured from the
onset of flow to the point when flow returned to baseline
(Fig. 1). Five consecutive beats were averaged for each
determination. The area under the velocity curve (velocity
integral) was determined by tracing from the baseline
around the velocity curve using a digitizing tablet linked
to a microcomputer (Fig. 1). Eight to ten beats were averaged for each determination.
Pulmonary artery systolic diameter was measured from
the parasternal short axis plane at the level of the pulmonary orifice, using a freeze frame facility and caliper
markers [14]. The diameters from five consecutive beats
were averaged and cross-sectional area (CSA)was calculated from the formula:
CSA(cm2)= n(D/2)2
where D is mean pulmonary artery diameter. Heart rate
was determined from the R-R interval of the electrocardiogram. Right ventricular CO was calculated according to the formula:
CO (litreslmin)= CSA (cm2)x VI (cm)x HR (beats/min)
where VI is the velocity integral and HR is the heart rate.
The values of right ventricular CO before and during
pregnancy have been reported previously [ 31.
MPAP was calculated from pulmonary AT and ET
according to the formula of Kitabatake et al. [ 101:
log MPAP (mmHg)= - 2.8 (AT/ET)+ 2.4
Total pulmonary resistance (TPR),expressed in resistance
units (RU),was calculated from the equation:
TPR(RU)=MPAP (mmHg)+CO(litres/min)
To determine the intra-observer measurement variability, pulmonary AT and ET from the first non-pregnant
recording were re-analysed by the same observer. Temporal variability was determined by one observer analysing
the two non-pregnant recordings obtained 1 month apart.
The within-subject intra-observer and temporal coefficients of variation for right ventricular CO have been
reported previously and were both less than 5% [ 141.
115
Pulmonary haemodynamics during normal pregnancy
Table 1. Mean Doppler haemodynamic results (n= 13)
The SEM was derived from analysis of variance. Abbreviations: PC, pre-conception; PN, postnatal, SR, Studentized range.
Gestation (weeks)
PC
137
304
0.45
13.8
AT (ms)
ET (ms)
AT/ET
MPAP
(-Hg)
Pulmonary
4.88
co (I/min)
TPR(RU)
2.85
’
PN
SEM
SR
5
8
12
16
20
24
28
32
36
38
133
297
0.45
13.6
133
296
0.45
13.5
129
289
0.45
13.8
130
293
0.44
14.5
128
293
0.44
14.7
126
289
0.44
14.8
126
289
0.44
14.5
125
286
0.44
14.7
125
285
0.44
14.5
124
283
0.44
14.5
135
298
0.45
13.9
2
10
4
13
0.01 0.03
0.9
3.5
5.31
6.16
6.52
6.91
6.98
6.95
7.00
7.12
7.13
7.19
4.80
0.11 0.46
2.55
2.17
2.11
2.07
2.10
2.11
2.07
2.08
2.05
2.02
2.91
0.16
0.57
Statistical analysis
DISCUSSI 0N
A repeated measures analysis of variance was performed for each variable using the statistical package
BMDP. Due to the problem of multiple significance testing, the difference between time points were compared
using the Studentized range at the 1%level [ 161:
The errors in velocity measurement using Doppler ultrasound during pregnancy have previously been reviewed
[ 141. When combined with cross-sectional echocardiography, this technique provides accurate and reproducible measurements of CO in pregnant subjects [ 14,
171. Doppler pulmonary velocity indices have also been
shown to correlate closely with MPAP in normal subjects
and patients with pulmonary hypertension [ 10-12, 151.
These indices are influenced by heart rate [18], which
changes during pregnancy [4], and also by the sampling
site [ 191. To minimize these sources of error, velocities
were consistently measured from the centre of the pulmonary artery and the ratio of AT to ET was used. Severe
tricuspid or pulmonary regurgitation also influences the
shape of the pulmonary velocity curve. None of the
patients in the present study had evidence of significant
regurgitant velocities. MPAP was calculated from the
regression equation of Kitabatake et al. [lo] because this
correlates the closest with invasively determined MPAP
( r = 0.90). Furthermore, in contrast to most other validatory studies, in which most of the subjects have had pulmonary hypertension, half of the subjects studied by
Kitabatake et al. [lo] had normal MPAP. However, no
validatory study has reported findings from a group of
purely normal subjects.
Three previous groups have reported cross-sectional
measurements of MPAP during normal pregnancy [6-81.
Our results are consistent with those of Bader et al. [7]
and Wallenburg [8] and are slightly higher than those of
Werko [6]. The present study is the first to report nonpregnant data from the same subjects. The results would
suggest that, relative to pre-pregnant values, MPAP does
not fall appreciably during pregnancy. The 29% reduction
in pulmonary vascular resistance reported here is also
consistent with previous reports [8, 201 and is of similar
magnitude to the reduction in resistance in the systemic
circulation recently reported by us [4]. In common with
systemic resistance the fall in pulmonary resistance occurs
during the first trimester. Interestingly in women with
severe pre-eclampsia, values of MPAP and pulmonary
vascular resistance [8, 21, 221 are similar to those
reported here and by Wallenburg [81 in normotensive
range = q(”)x [s + Jn],
where qV)is the critical value for comparing two time
points, s2 is the residual mean square with v degrees of
freedom and n is the number of subjects. Thus any change
greater than the Studentized range was considered statistically significant.
A components of variance analysis was performed to
determine the reliability of measurements made by one
observer (intra-observer variability) and the reproducibility of measurements made 1 month apart (temporal variability). Using these estimated variances the
within-subject coefficients of variation were calculated for
pulmonary AT and ET.
RESULTS
Serial measurements of velocity and diameter were
obtained from all subjects. The Doppler echocardiographic results are shown in Table 1.
Pulmonary AT and ET fell during pregnancy, the
decrease being statistically significant from 24 weeks
gestation. ET was also significantly reduced at 12 weeks
of pregnancy. Both returned to pre-pregnancy levels after
delivery. Thus there was no significant change in the AT/
ET ratio and in the calculated MPAP (Fig. 2 6 ) during
pregnancy. Right ventricular CO increased during pregnancy (Fig. 2a), the increase being significant by 8 weeks
gestation. Calculated TPR fell during pregnancy (Fig. 2c).
The decrease was significant, relative to pre-pregnancy
values, by 8 weeks gestation and thereafter there was no
further change. By 6 months after delivery pulmonary
vascular resistance had returned to pre-pregnancy values.
The intra-observer and temporal coefficients of variation for pulmonary AT were 5% and 8%, respectively.
The corresponding values for pulmonary ET were 3%
and 5%.
S. C. Robson et al.
116
4’1
PC
I
I
I
I
I
I
‘
‘
1
1
‘
8 12 16 20 24 28 32 36 38 PN
5
pulmonary vasculature is unclear. Both sex steroid
hormones have both been implicated in the diminished
pulmonary vascular reactivity that occurs during pregnancy [ 2 5 ] .This action may be mediated by an increase in
prostacyclin [25]and it is interesting to note that pulmonary vascular resistance has been reported to fall during
continuous infusion of prostacyclin [26]. Recently, calcitonin-gene-related peptide has been shown to be a potent
vasodilator of human pulmonary arteries and veins [27].
This peptide increases during normal pregnancy [28] and
the increase is evident during the first trimester, the time
when pulmonary vascular resistance appears to fall.
ACKNOWLEDGMENTS
This work was supported by a grant from Birthright.
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10’1
I
I
PC
5
I
I
I
I
I
I
I
1
1
8 12 16 20 24 28 32 36 38 PN
8 12 16 20 24 28 32 36 38 PN
Gestation (weeks)
Fig. 2. Serial measurements of ( a ) pulmonary flow, ( b )
PC
5
MPAP and (c) TPR during pregnancy ( n= 13). Values
shown represent means and 95% confidence intervals.
Abbreviations: PC, pre-conception; PN, postnatal.
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