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PATHOPHYSIOLOGY AND NATURAL HISTORY
EXERCISE PHYSIOLOGY
Dilfering mechanisms of exercise flow augmentation
at the mitral and aortic valves
ANIS RASSI, JR., M.D., MICHAEL H. CRAWFORD, M.D., KENT L. RICHARDS, M.D.,
AND JACELYN F. MILLER, R.D.M.S.
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ABSTRACT To determine the mechanisms by which blood flow increases across the mitral and aortic
valves during exercise, 18 normal men were studied during graded supine and upright bicycle exercise
at matched workloads. Mitral valve orifice and ascending aortic blood velocities were recorded by
Doppler echocardiography during steady states at each stage of exercise. Parasternal two-dimensional
echocardiographic imaging of the ascending aorta adjacent to the aortic valve orifice and the mitral
valve orifice at the tips of the valve leaflets was used to calculate changes in cross-sectional area during
exercise. Heart rate increased from rest to exercise from 67 to 150 beats/min (124%) during supine
exercise and from 72 to 147 beats/min (104%) during upright exercise. Stroke volume increased 20%
during supine and 46% during upright exercise; the increase in stroke volume was statistically significant
when rest and exercise were compared and when the magnitude of change was compared vs position
(p < .05). The increase in stroke volume measured at the ascending aorta was accomplished by an
increase in the velocity-time integral (+ 15% supine and + 48% upright, p < .05), with little change
in aortic cross-sectional area (5% supine and 0% upright, p = NS). By contrast, the increase in flow
rate measured at the mitral valve was predominantly due to an increase in mean diastolic cross-sectional
area (+ 29% supine and 34% upright, p < .05); the velocity-time integral did not increase significantly
( - 10% supine and 4% upright; p = NS). The data contrast the mechanisms by which aortic and mitral
valve flow increase with exercise, and demonstrate an increase in cross-sectional area at the mitral valve
orifice and the importance of an increase in velocity-time integral at the aortic valve. These observations
support the use of changes in the heart rate times velocity-time integral as an indicator of changes in
cardiac output at the aortic valve, but stress the importance of serial cross-sectional area measurements
at the mitral valve orifice in the assessments of changes in cardiac output.
Circulation 77, No. 3, 543-551, 1988.
IF THE LEFT VENTRICLE is conceptualized as a
conduit for blood with an inlet at the mitral valve and
an outlet at the aorta, then in the absence of valvular
regurgitation or interventricular shunting, the stroke
volume through the mitral orifice equals the output from
the aorta. During isotonic exercise, increases in both
stroke volume and heart rate are responsible for the
increase in cardiac output.1 The mechanism by which
the stroke volume is increased at both valves must
involve an increase in cross-sectional area and/or an
increase in the product of blood velocity and time (the
velocity-time integral). Examination of the changes in
time allowed for flow across the mitral vs the aortic
valve suggests that the mechanisms available to inFrom the Division of Cardiology, University of Texas Health Science
Center and Veterans' Administration Hospital, San Antonio.
Supported in part by the Veterans' Administration.
Address for correspondence: Michael H. Crawford, M.D., Department of Medicine, Division of Cardiology, University of Texas Health
Science Center, 7703 Floyd Curl Dr., San Antonio, TX 78284-7872.
Received Aug. 21, 1987; revision accepted Nov. 20, 1987.
Vol. 77, No. 3, March 1988
crease flow may differ at the aortic and mitral valves,
since as heart rate increases diastolic mitral filling time
per cardiac cycle decreases exponentially.2
Studies in humans have documented an increase in
diastolic left atrial pressure and a concomitant decrease
in left ventricular diastolic pressure during exercise3-5;
thus, the driving pressure filling the left ventricle is
increased. The exercise-induced increase in filling
pressure would be expected to increase mitral valve
blood velocity, but could also increase mitral valve
cross-sectional area. Consideration of the phasic char-
acteristics of mitral valve orifice area during diastole
reveals an M-shaped configuration with maximal opening in early diastole and a second period of opening in
late diastole. Increases in mitral valve flow also could
be accomplished by increasing the mitral valve velocity
and/or cross-sectional area during the period of middiastole. Conditions in the aorta are different, with a
relatively constant cross-sectional area and a linear
decrease in flow time noted during exercise.6 7 Thus,
543
RASSI et al.
increase in mean velocity would be expected to be
the mechanism by which stroke volume is increased at
the aortic valve.
Accordingly, the purpose of this study was to use
noninvasive Doppler and imaging echocardiographic
techniques to contrast the mechanisms by which flow
is increased across the mitral valve orifice and the
ascending aorta during isotonic exercise. Use of both
supine and upright bicycle exercise allowed for the
examination of these mechanisms under two different
ventricular loading situations. It was hoped that these
observations could be used to simplify the complex
measurements required to make accurate estimations of
exercise-induced changes in cardiac output at these
sites.
an
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Methods
Subject selection. We studied 26 healthy male volunteers
who were selected from a larger group because of excellent
Doppler echocardiograms in the supine and upright positions at
rest. Eight were subsequently excluded because of unsatisfactory
imaging and/or velocity tracings during exercise. The remaining
18 represented our final population and their ages ranged from
22 to 37 years (mean 28 + 4 years). Physical fitness varied from
subject to subject, but none could be considered a trained athlete.
Written informed consent was obtained on a form approved by
Institutional Review Board.
Exercise protocol. After an initial abbreviated exercise study
to familiarize the subjects with the study procedures, all underwent graded, continuous exercise testing in both the supine and
upright positions on different days but under similar conditions.
Upright exercise was performed on a mechanically braked
Monark bicycle ergometer and supine bicycle exercise was
performed on a Quinton Uniwork Ergometer model 844,
mounted on the foot of a bed. Equivalent workloads for all
subjects were used during the supine and upright exercise, starting at 150 kilopond-meters (kpm)/min and then increasing to
300, 450 and 750 kpm/min. The subjects exercised continuously
for 3 to 6 min at each level of work, depending on the time
required for an adequate echo-Doppler data acquisition, which
began after the second minute of each exercise stage. The total
exercise time was not significantly different between the two
positions (18.4 ± 2.6 min upright vs 18.0 ± 1.4 min supine).
The electrocardiogram was monitored continuously. Cuff blood
pressure was recorded at rest, during each stage of exercise, 30
sec after exercise, and then at 1 min intervals for a total of 6 min
of recovery. Systolic blood pressure increased progressively
during exercise and declined rapidly during recovery. Since
blood pressure was not significantly different between the two
positions it will not be considered further in this report.
Doppler echocardiographic examination. Two commercially available Doppler echocardiographic systems with both
continuous and pulsed-wave capabilities (Advanced Technology
Laboratory, Mark 600 and Ultramark 8) were used in this study.
Two-dimensional imaging and mitral Doppler flow velocities
were obtained with a 2.25 MHz mechanical transducer. Aortic
flow velocities were quantified by continuous-wave Doppler
with a 2.25 MHz nonimaging dedicated transducer. Examination and recordings proceeded as follows. First, with the imaging transducer placed at the cardiac apex, an apical four-chamber
view of the heart was obtained. The Doppler cursor was initially
aligned parallel to the apparent direction of flow and the sample
our
544
volume was positioned just distal to the mitral valve leaflets in
diastole. From this starting point, the system was switched to
the Doppler mode, and the highest mitral velocities with least
spectral dispersion were searched with aid of the audio signal
and the spectral display. Maximum velocities were noted when
the center of the sample volume was between just distal and just
proximal to the mitral leaflets. At times, minor adjustments in
transducer angulation and/or sample volume position were
required to maximize the graphic quality of the Doppler signal.
Sampling position was easily checked by switching the instrument back to the real-time imaging mode. Sample volume length
was adjusted to optimize the quality of the spectral display and
was best between 5 and 10 mm. Hard copies of the spectral
velocity displays, with simultaneous electrocardiograms, were
obtained at a paper speed of 100 mm/sec. Since the maximum
velocity recorded through the normal mitral valve orifice in this
study was 182 cm/sec, aliasing was avoided by moving the
baseline to the bottom of the tracing and using the maximal pulse
repetition frequency (shallowest depth setting) possible. The
imaging/Doppler transducer was maintained at the cardiac apex
throughout the study. Immediately after the acquisition of the
mitral Doppler data, another operator recorded the aortic systolic velocities by placing the continuous-wave transducer at the
suprasternal notch. Angling the transducer with the use of auditory and visual monitoring allowed location of maximal velocities across the proximal ascending aorta. Again the velocity
tracings were recorded at 100 mm/sec paper speed. Thereafter,
the transducer was completely removed from the suprasternal
notch. With this technique, the intercept angle was assumed to
be minimal and no angle correction was made to calculate mitral
and aortic velocities. Wall filters were set at 200 to 400 Hz.
The above procedure was performed at rest and was repeated
at each stage of exercise and sequentially during recovery. Data
obtained from subjects in the supine position, at rest, and at
recovery were obtained with their legs raised onto the bicycle
pedals. The recordings during upright exercise were obtained
with the subjects leaning slightly forward on the bicycle with
their arms resting on the top of an adjustable table that the
operator also used for support.8
Although the change in mean mitral orifice area during exercise could have been inferred from the velocity data at each valve
site by use of the continuity equation and assuming that there
was little change in aortic area, we were also interested in
observing the changes in orifice size during diastole as exercise
progressed. However, we found it difficult to move the imaging
transducer to the parasternal position and back to the apex and
maintain imaging quality during exercise. Therefore, for this
purpose, 10 of the 18 subjects repeated the same exercise protocol (supine and upright) on different days and two-dimensional
echocardiograms in the standard parasternal long and short axis
were recorded on videotape while they were at rest and during
exercise and recovery for subsequent analysis. An M mode
echocardiogram of the mitral valve at a paper speed of 100
mm/sec was also obtained by adjusting the M mode cursor across
the middle of the maximal mitral orifice area as observed in the
short-axis view. No significant difference in exercise duration,
heart rate, or blood pressure was observed between the two
exercise tests in each position in this subgroup.
Doppler echocardiographic measurements and analyses.
All measurements were made with a digitizing pad (Summagraphics Model ID-2-CTR1 1), and a microcomputer (IBM-PC)
controlled by a dedicated software program (Micro-Sonics, Inc.
Version 2.5). For the data recorded on tape (two-dimensional
images), a videocassette system equipped with a frame-byframe bidirectional search (JVC model BR 6400U) permitted
analysis in a slow-motion, real-time, or stop-frame format.
Doppler spectral tracing measurements of both aortic and
CIRCULATION
PATHOPHYSIOLOGY AND NATURAL HISTORY-EXERCISE
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mitral flows included velocity-time integrals, flow time, and
flow time fraction of the cardiac cycle. The cardiac cycle length
and corresponding heart rate were also obtained from the simultaneous electrocardiogram. Aortic and mitral velocity-time integrals, systolic ejection time (ST), and diastolic filling time (DT)
were calculated as we have previously described.9 The systolic
fraction of the cardiac cycle time (CT) was calculated as ST/CT
x 100, and the filling fraction of the cardiac cycle as DT/CT
x 100. All beats analyzed were those recorded during the
expiratory phase of respiration.
The maximal mitral orifice area was measured from the
parasternal short-axis view by tracing the innermost border of
the largest orifice when both leaflets were well visualized and
separated from the ventricular walls. Long-axis imaging confirmed that leaflet separation was constant for the distal 10 mm
of the leaflets in early diastole. Thus, the orifice area and Doppler
recordings were derived from the same anatomic site. Stroke
volume and cardiac output at the mitral area was then calculated
by the method of Fisher et al.`0 Aortic valve diameter was
measured from a parasternal long-axis view by the trailing
edge-to-leading edge method just distal to the valve leaflets, as
validated by Gardin et al.`1 Stroke volume and cardiac output
was calculated by the method of Huntsman et al.`2
All reported measurements were performed by an experienced
PHYSIOLOGY
single observer in a blinded manner and represent the average
of three different cardiac cycles at each stage.
Data analysis. All data were analyzed by a two-way analysis
of variance for repeated measures. Mean differences were determined for each measure over time in one exercise position and
between exercise positions at the same time by the use of the
Student-Newman-Kuels mean comparison test based upon the
range.13 Mean values are expressed SD and p < .05 was
considered indicative of a significant difference. In five subjects
mitral and aortic orifice area determinations at rest and at each
exercise stage were made by two observers independently to
estimate interobserver variability. Also, four subjects underwent
repeated exercise imaging studies and the same observer measured the mitral and aortic orifice area on both occasions. The
absolute difference between all paired measures was divided by
their mean and expressed as percent variability.
Results
Effect of exercise on mitral stroke volume. Table 1 displays the mean values for each measurement at each
stage of exercise and recovery in both positions. Statistical significance over time in each position is indi-
TABLE 1
Echocardiographic-Doppler mitral data
Stage
REC III
Rest
150 kpm
300 kpm
450 kpm
750 kpm
REC I
REC II
67± 12
95+±1A,B
±1A,B
105+
119±15A,B
150±15A,B
122±20A,B
98+ 16A,B
p<.05
NS
NS
NS
NS
NS
NS
NS
13A,B
101j13A,B
119±15A,B
147 ± 20A,B
118 ± 19A,B
97 + 15A.B
90 ± 13A,B
496± 173
p<.05
431± 100
277 52A,B
NS
293 ± 56A.B
239 +40A3B
NS
256 ± 44A,B
204± 36A,
161±22A.B
NS
174± 29A,B
231
294 l 102A.B
NS
290 ±67A.B
52±7
NS
43+4A,B
NS
41±3 A
NS
50 ±4
44±+ 3A,B
42± 3A,B
21.5±3.7
p<.01
17.6± 3.0
20.5 ± 2.9
NS
19.3 3.1AB
S
4.2±0.9
4.8 1.0A,B
U
p<.01
3.5 ±0.5
p<.05
4.20.8A,B
99 ± 28
p<.01
65 ± 15
106±26A.B
6.1± 1.4
p<.01
4.4±0.9
9.8
HR (beats/min)
S
U
DT (msec)
S
U
DT/CT (%)
S
U
73 ± 12
93
NS
213 ± 31AB
56A,B
NS
233 + 38A'B
46+6A
40±3A
NS
45±5A,B
42 ±2A
42 ± 3A
45 ±4AB
20.5 ± 3.3
NS
19. 3±31A
20.0 ± 3.7
NS
19.2±2.9A
19.3 ± 3.1A
NS
18.3 ±2.9
5.1± 1.0kA
5.2± 1.OA
p<.05
O
5.4t0.8A
p<.05
5.0±0.8AB
p<.01
4.3±0.8A
4.5 ±0.7
4.7±06A0B
112±28A
p<.05
111+29A
11020A
p<.05
NS
NS
NS
45 ±5A
93± 12A
290 62A
NS
309 ±62A
44±4A
NS
A
VTIm (cm)
S
U
20.0±4,3A
p<.01
17.0± 3.0
19.1± 3.2A
p<.01
16.8 ±3.2
4.8±0.8A
4.6±0.7A
4.2+0 6A,B
p<.05
4 0+0.7A
3.9±0.7A
108±16
102 ± 26
20.6± 3.3
p<.01
17.8± 2.9
MVOc (cm2)
p<.05A
p<.05
SVm (ml)
S
U
p<.05
84 ± 23A,B
86 + 23A
p<.05
88 ± 23A
89±+ 22A
p<.01
75 ±19A,B
16.1 3.0AB
p<.05
12.9+3 3A,B
12.2± 1.7A.B
p<.01
8 9±2.5A,B
92 ± 18B
70± 17A
p<.01
66± 21
9.2± 1.3A,B
p<.01
6.5+ 1.6A,B
8.1 ± 1.3A,B
p<.01
5.7+ 1.7A
p<.01
COrn (1/mmn)
5
U
1.8A,B
11.3 23A.B
p<.01
p<.05
7.5+ 1.9A,B
8.5+2.1A
12.7 23A,B
p<.05
10.5+2.7A,B
All data are mean ± SD.
HR = heart rate; MVOc = mean mitral valve orifice area; REC = recovery (I = 0-2 min after exercise; II
mitral stroke volume; U = upright; VTIm = mitral velocity-time integral.
Ap < .05 vs rest; Bp < .05 vs preceding level.
Vol. 77, No. 3, March 1988
=
2-4; III = 4-6); S - supine; SVm =
545
RASSI et aL
Supine Exercise .Mitral Doppler
160
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E
C)
1..II:0011...:2..:::
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4012010080-
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60
PIE,
4020
o
...
a
...
Q.0
.......
EG
300 k:prn
Rest
150 kpm
4 50 kpm
RECI
750:kPm
FIGURE 1. Representative single-beat Doppler velocity recordings at rest, during exercise, and during recovery. See text for
details. ECG electrocardiogram; REC recovery.
=
RECK
=
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cated next to the mean values by symbols. Significant
differences in values at the same time during exercise
but in the two different positions is designated in the
row between the values.
Heart rate increased progressively during exercise in
both positions (124% maximum supine, 104% maximum upright). Diastolic flow time decreased progressively during exercise. DT/CT also decreased significantly during the first two stages of exercise, then
remained constant until the end of exercise. Although
the diastolic flow augmentation coincident with atrial
contraction was no longer discernible in the later stages
of exercise, peak mitral velocity always occurred early
in diastole (figure 1). Despite an increase in peak
velocity, the mitral velocity-time integral changed little
during exercise because of the truncation of diastolic
flow time. In fact, in the supine position mitral velocity-time integral was significantly decreased at peak
exercise as compared with rest. Mean mitral valve
orifice area increased significantly during early exercise
FIGURE 2. Digitized stop-frame echocardiographic images of the
maximum
early diastolic mitral leaflet orifice from the
parasternal short -axis view at rest (tpper left) and at the first (upper right), second (lower left), and third stage of exercise (lower
right).
546
CIRCULATION
PATHOPHYSIOLOGY AND NATURAL HISTORY-EXERCISE PHYSIOLOGY
Echo- Doppler mitral
Supine exercise
Echo - Doppler mitrol
Upright exercise
60+
* MVOc
* MVOc
A SVn
* VTIm
SVm
A
70 -
* VTIm
21
60 -
60 4
so T,
40
E
O
_
50
E
F
c
30 t
+1
C c
CC
U
= 0 20
0
Ci
10,
°
A0
a-
O- ,
1
- 20o
-
1
20+
1
-
-30
20 +
11
- 30
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REST
450kpm
SOOkp.
0
450
kpn
TSOhlpm
REC
REC
n
REC
m
REST
iOkDa
Stage
300hkp.R
450kpa
750 prp
RECI
RECU
RECM
Stage
FIGURE 3. Percent change in three mitral echo-Doppler measures during supine (left) and upright (right) exercise as compared
with rest. See text for details. MVOc = mean mitral valve orifice area; SVm stroke volume derived from mitral Doppler
and echocardiographic data; VTLm = mitral velocity-time integral.
=
and remained larger than the resting value through the
end of exercise (+29% supine and + 34% upright,
figure 2). Consequently, mitral stroke volume also
increased significantly during early exercise and remained higher than the resting value throughout exercise (figure 3). Cardiac output calculated from the
mitral data (COm) increased progressively during exercise (164% supine and 193% upright).
decreased less rapidly in supine subjects because of a
maintenance of the mitral velocity-time integral, since
mitral valve orifice area decreased similarly in both
positions. COm was consistently lower throughout
exercise and recovery in the upright position because
mitral valve orifice area was smaller.
aortic stroke volume (table 2).
upright position throughout exercise and recovery.
Also, the aortic velocity-time integral was less in
upright subjects. However, the aortic cross-sectional
area was not different between the two positions. Thus,
aortic stroke volume and COa were lower in upright
subjects because of the reduced flow times and velocities in this position. During recovery aortic stroke
volume declined less rapidly in supine subjects because
of less change in the aortic velocity-time integral
(figure 5).
Effect of exercise
on
Although systolic flow time progressively decreased
during exercise, ST/CT increased significantly during
exercise. The aortic velocity-time integral increased
during early exercise and remained significantly higher
than the resting value throughout exercise (+ 15%
supine and + 48% upright). Aortic cross-sectional area
did not change appreciably during exercise. Consequently, aortic stroke volume increased significantly
early in exercise and remained higher than the resting
value throughout (figure 4). Cardiac output from the
aortic data (COa) also increased progressively during
exercise (194% supine and 220% upright).
Influence of exercise position
on
mitral stroke volume
(table 1). Except for a slightly faster heart rate at rest in
the upright position, there was no significant difference
in any of the time intervals at the two positions. The
mitral velocity-time integral was not different in the two
positions, but mitral valve orifice area was consistently
smaller in upright subjects; consequently, so was mitral
stroke volume. During recovery, mitral stroke volume
Vol. 77, No. 3, March 1988
Influence of exercise position
on
aortic stroke volume
(table 2). ST and ST/CT were significantly less in the
Reproducibility of mitral orifice determinations. Two
observers analyzed the same supine exercise study
recordings from the mitral orifice in the short-axis view
and measured the maximum area. The mean difference
was 0.45 cm2 or 4.0% (interobservervariability). In the
four subjects who repeated upright exercise for mitral
imaging, mean difference in mitral orifice area measurements by the same observers was 0.50 cm2 or 6.2%
(intrasubject variability). The intraobserver difference
in the mean resting and exercise aortic diameters in the
parasternal long-axis view was 0.04 + 0.025 cm or
547
RASSI et al.
TABLE 2
Echocardiographic-Doppler aortic data
Stage
Rest
150 kpm
300 kpm
65+ 13
94+±1AB
104± 12A,B
120+
14A,B
152± 15A.B
p<.01
72±12
NS
91 + 14AB
NS
101 + 14A.B
NS
118 ± 16A.B
NS
147 ± 19A,B
299 + 40
267 ± 31 A,B
255 ± 27A.B
235 + 30A,B
p<.01
p<.Ol
p<.OS
248 ± 37
242 -+ 34
31 ± 4
450 kpm
750 kpm
REC I
REC II
REC III
HR (beats/min)
S
U
ST (msec)
S
U
17AJB
94+ 16A,B
91 ± 12A
106±19A,B
NS
93 + 16B
NS
88 ± 14A
206 ± 25A,B
222 ± 23A,B
246 ± 29A,B
261 ± 3 1 A,B
p<.OS
p<.OS
p<.Ol
p<.Ol
234 ± 39A
214 ± 34A,B
189 ± 32A,B
196 ± 38A
213 + 39A,B
224 ± 43A
44 ± 4A,B
p<.Ol
39 ± 6AB
46 ±5A,B
p<0l
42 +6AB
52 ± 6A,B
p<.Ol
46 7AB
40±+ A,B
p<.01
34 +6AB
38 ± 5A
p<.Ol
33 ± 6A
39 ± 4A
29 + 4
41 ± 4A-B
p<.Ol
36 ± 5A,B
21.4 ±4.9
25.0+ 5.3A,B
25,5 ± 5.6A
25.7 + 5.9A
24.6 ± 5.4A
25.6 ± 5.7A
25.0 ± 5.7A
23.6 +55A,B
p<.0l
14.6 +4.6
p<.Ol
19,4+69A,B
p<.Ol
210+74A.B
21.6+ 7.3A
p<.OS
21.6+ 7.0
p<.Ol
18.3 ±5 7A,B
p<.Ol
17.0 ±66A
p<.Ol
15.6+ 6.
4.3±0.6
NS
4.3+0.6
4.4+0.6
NS
4.3+0.6
4.4+0.6
NS
4.2+0.6
4.4±0.7
NS
4.3±0.6
4.5±0.7A
NS
4.3±0.6
4.4±0.7
NS
4.3±0.6
4.4±0.7
NS
4.3+0.6
4.3±0.6
NS
4.3+0.6
88 ± 22
p<.01
62 ± 19
105 ± 25A,B
p<.01
85 ± 30AB
106 + 26A
p<.05
89 ± 32A
107 ± 25A
p<.05
90 ± 29A
103 ± 19A
NS
90 + 31 A
105 ± 20A
101 ± 23A
p<.01
73 30A
96 ± 23A
5.2 +0.8
p<.01
4.1 +0.7
9.6± 1.6A,B
p<.01
7.4+2.3A B
10.7 +2.0A,B
p<.05
8.9±3.1A
12.4 ±2.2A,B
p<.05
15.3 +2.7A.B
NS
13.1 44AB
10.9±+ 19A,B
90+1 7A,B
p<.01
p<.01
6.2+2 3A.B
110+
NS
p<.Ol
ST/CT (%)
S
p<.05
U
VTIa (cm)
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S
U
A-CSA (cm2)
S
U
SVa (ml)
S
U
COa (1/min)
S
U
p<.Ol
10.6±3.6A,B
All data are mean + SD.
A-CSA = aortic cross-sectional area; HR heart rate; REC = recovery (I
aortic stroke volume; U = upright; VTIa aortic velocity-time integral.
Ap < .05 vs rest; Bp < .05 vs preceding level.
=
p<.01
78 ± 26A.B
7.9+2 6A,B
0-2 min after exercise; II
=
2-4; III
=
p<.0OI
32+ 6
p<.05
69 ± 30
8.3 ± 1.6A
p<.01
5.7+22A
4-6); S
=
supine; SVa
=
1.5% and that for the calculated orifice area was 0.17
± 0.11 cm2 or 2.9%. The intrasubject difference in
aortic diameter was 0.11 + 0.08 cm or 4.4% and the
calculated area difference was 0.43 + 0.34 cm2 or
8.6%. There was no difference in the variability of
resting as compared with that of exercise values.
Discussion
Our data demonstrate that stroke volume increases
early during exercise, which necessitates higher volume flow at the aortic and mitral orifices. Increased
volume flow per cycle at the aortic orifice is accomplished principally by an increase in the velocity-time
integral. The increase in aortic velocity-time integral
is due in part to an increase in systolic time per cycle,
but more importantly to an increase in systolic velocity
(figure 4). By contrast, increased mitral volume flow
is accomplished mainly by an increase in the maximum
diastolic mitral valve orifice. The mitral velocity-time
548
integral actually decreases in the supine position,
despite increases in velocity, because of the marked
abbreviation of DT (figure 3).
Our aortic Doppler echocardiographic results during
exercise agree with those of previous studies.14-16 In
addition, our mitral Doppler echocardiographic findings are consistent with experimental studies in dog
preparations. Fisher et al.10 demonstrated in five openchest dog preparations in which cardiac output was
controlled by a roller pump a relationship between
maximum diastolic mitral valve area by two-dimensional echocardiographic imaging and cardiac output (r
= .85 to .99). However, in the smallest dog mitral
valve area plateaued at flows greater than 4 liters/min.
Thus, they hypothesized that changes in mitral orifice
size must eventually reach a maximum in all animals
if the flow is high enough. Stewart et al..17 using a
similar study design, also showed that maximum diastolic mitral valve area failed to increase in their dogs
CIRCULATION
PATHOPHYSIOLOGY AND NATURAL HISTORY-EXERCISE PHYSIOLOGY
Echo- Doppler aortic
Supine exercise
Echo - Doppler aortic
Upright exercise
* A-CSA
A SVa
* VTla
so
70
Ef
70
t
60
60 t
SO-o.
%n ff
t
40-4-
10
E
* A-CSA
* SVa
* VTIa
50±
E
40'
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_-0
030
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10t
lo0.
-
20-
20-
-
30-
30J
T
REST
S50Rpm
300Rpm
4501pm
750Rpm
REC
RECI
REC m
Stage
REST
450Rkpm
300pm
450Rpm
750kpm
RECI
RECH
REC M
Stage
FIGURE 4. Percent change in three aortic echo-Doppler measures during exercise. Left, supine data; right, upright data. A-CSA
= aortic cross-sectional area; SVa = stroke volume calculated from aortic echo-Doppler data; VTIa = aortic velocity-time
integral. See text for details.
after flows of 4 liters/min. They also pointed out that
since the mitral orifice increased, velocity changes with
increasing flow were much less at the mitral valve as
compared with at the aortic valve, where orifice size
changed very little at higher flows.
Our results also demonstrate that at identical workloads cardiac output is higher in the supine position.
This was a result of higher stroke volume, since heart
rate was not significantly different during exercise in the
two positions. Systolic flow time per cardiac cycle was
consistently higher in supine subjects. Consequently,
aortic velocity-time integral was higher in the supine
position. Aortic orifice area was no different in the two
positions. Interestingly, diastolic time per cycle and
mitral velocity-time integral were no different in the
two positions. Thus, mitral stroke volume was higher
in supine subjects because of a significantly larger
mitral orifice size in this position.
It is well known from previous exercise physiology
studies that cardiac output and stroke volume are higher
during supine than during upright exercise at the same
workloads.18 Previous investigators have ascribed this
difference to less diastolic filling rather than reduced
left ventricular performance during upright exercise. 9-2' This conclusion is supported by our data
since mitral orifice area was considerably smaller in the
upright position. Intracardiac pressure values from
other studies have documented lower values during
upright exercise, but the effective filling pressure (left
Vol. 77, No. 3, March 1988
atrium-ventricle gradient) is unknown.3 Since peak
mitral velocities were higher in our supine subjects, the
effective filling pressure may have been higher in this
position.
Data collected by both Doppler techniques during
recovery from exercise showed a rapid decrease in
stroke volume in the upright position and a more gradual decrease in the supine position. This difference in
recovery was largely explained by a more rapid
decrease in the velocity-time integral at both valve sites
in the upright position. Mitral valve orifice area
returned toward resting values at a similar rate in both
positions. Recovery values obtained by the two Doppler techniques cannot be compared because recovery
is not a steady-state condition and the Doppler data
from each valve site were collected sequentially. Our
recovery data are in agreement with those from previous hemodynamic studies that have shown that stroke
volume decreases rapidly after cessation of upright
exercise, but not supine exercise.22 23 More recently
Gardin et al.16 showed, using a pulsed Doppler technique, that the highest aortic velocity-time integral
occurred at 2 min of recovery. Our continuous-wave
aortic data are consistent with this observation.
A limitation of our study was that Doppler velocity
recordings and orifice imaging by two-dimensional
echocardiography could not be done simultaneously at
two valve sites or during the same exercise study.
Simultaneous recordings with two machines is impos549
RASSI et al
C)
Wi
'I,
N.1
EU,
Uprignt Exercise Aortic Doppler
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(,
U,1
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0
80400
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...
ResT
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.
l3UKpm
f75Okpm
REC I
RE8CIM
FIGURE 5. Representative aortic Doppler velocity recordings obtained in patients at rest and during selected stages of exercise
and recovery in the two exercise positions. See text for details.
sible because of interference from the two sound
beams. However, heart rate and blood pressure measurements confirmed steady-state conditions after 2
min of each exercise stage. We also found that
moving the transducer position impaired the ability to
gather high-quality data during exercise. Thus, with
three transducer positions necessary (suprasternal,
parasternal, and apical) to gather the data necessary for
this study, two exercise studies in each position were
required. Since other studies have shown little change
in aortic orifice area during alterations in cardiac output, we could have deduced the increase in mean mitral
valve orifice area from the Doppler velocity data
using the continuity equation.24 25 We also could
have measured mitral valve leaflet separation diameter
in the apical four-chamber view and calculated
orifice area. but this would have required assuming
the geometry of the orifice during exercise. Consequently, we decided to directly evaluate orifice area in
a subgroup with excellent short-axis mitral valve
images during a repeat exercise study. Although
there was no significant difference in the heart
rate and blood pressure response during each of the
two exercise sessions in each position, differences
in subject response between studies cannot be
550
excluded and may have influenced the results.
Several Doppler echocardiographic techniques have
been used successfully to estimate stroke volume and
cardiac output, including recording from the mitral
anulus.26 However, preliminary pulsed Doppler studies
in our normal subjects showed that peak mitral valve
velocities at rest and during exercise occurred from just
distal to just proximal to the leaflet tips. This observation is consistent with those of other investigators.10' 17, 26 Also, Zhang et al.27 have shown that
maximum mitral velocity is the same at the leaflet tips
as it is 1 cm above the tips, but is lower at the anulus.
Thus, we assumed that the flow limiting site in normal
subjects was best approximated by measuring orifice
area at or near the mitral leaflet tips. This was readily
accomplished since there was usually only one transducer position that would identify both mitral leaflets
separate from the ventricular walls (figure 2). Recently,
stroke volume estimates from aortic Doppler recordings during exercise have been shown to correlate with
those made by invasive techniques.28 In our study,
stroke volume measurements were not significantly
different by aortic and mitral Doppler methods during
exercise. However, since we did not have an invasive
standard in our study, we have emphasized the relative
CIRCULATION
PATHOPHYSIOLOGY AND NATURAL HISTORY-EXERCISE PHYSIOLOGY
Downloaded from http://circ.ahajournals.org/ by guest on June 18, 2017
changes observed during exercise, which we believe to
be accurate.
It is unlikely that the measurements made in this
study would be of value for routine clinical studies
because of their complexity. However, these observations suggest a potential method for simplification of
the analysis of exercise-induced changes in cardiac
output. Our data contrast the mechanisms by which
aortic and mitral valve flow increase with exercise and
demonstrate an increase in cross-sectional area at the
mitral valve orifice and the importance of an increase
in the velocity-time integral at the aortic valve orifice.
These findings support the use of changes in heart rate
times velocity-time integral at the aortic valve as indicators of changes in cardiac output for clinical use.
However, the importance of orifice area in accommodating changes in cardiac output during exercise at the
mitral valve implies that disease states that directly alter
mitral valve mobility may impair exercise capacity.
This concept is the focus of ongoing research in our
laboratory.
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551
Differing mechanisms of exercise flow augmentation at the mitral and aortic valves.
A Rassi, Jr, M H Crawford, K L Richards and J F Miller
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Circulation. 1988;77:543-551
doi: 10.1161/01.CIR.77.3.543
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