Download Direct Determinations of Aortic Blood Flow

Direct Determinations of Aortic Blood Flow
in Patients with Aortic Regurgitation
Effects of Alterations in Heart Rate, Increased
Ventricular Preload or Afterload, and
Isoproterenol
By ROBERT K. BRAWLEY, M.D.,
AND
ANDREW G. MoRRow, M.D.
With the technical assistance of Harry W. Seipp, Jr., and David E. Cobb
SUMMARY
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Instantaneous ascending aortic blood flow and left ventricular and central aortic
determined at the time of operation in nine patients with severe aortic
regurgitation. In six, the heart rate was controlled and increased by electrical stimulation between 50 and 170 beats/min. The relative duration of diastole decreased, and
that of systole increased at faster heart rates. The mean systolic ejection rate fell, and
regurgitant flow rates remained relatively constant. Thus, the per cent regurgitation was
not reduced at faster rates. Following isoproterenol administration, the faster heart rate
lengthened the relative duration of systole, abbreviated that of diastole, and increased
the systolic ejection rate. Net result was an increased total forward flow and a reduced
per cent regurgitation, but when the heart rate was held constant, the total forward
stroke volume was ejected more rapidly, but the total forward and regurgitant flows
per beat and per minute, and consequently the per cent regurgitation did not change.
Assessments of left venticular function also were made in two patients.
pressure were
ADDITIONAL INDEXING WORDS:
Atropine
Left ventricular function
Electronic pacemaker
HE magnitude of regurgitant blood flow
through an incompetent aortic valve
is principally determined by the area of the
regurgitant orifice in the aortic valve, the diastolic pressure gradient between the aorta and
left ventricle, and the duration of diastole.
These determinants of regurgitant flow, formulated mathematically by Gorlin and Gorlin
in 1955,' were certainly appreciated in 1832
by Corrigan,2 who wrote: "The danger of the
disease is in proportion to the quantity of
blood that regurgitates, and the quantity that
regurgitates will be large in proportion to the
degree of inadequacy of the valves, and to
the length of pause between the contractions
of the ventricle during which the blood can
be pouring back."
It has long been recognized that an increase
in heart rate reduces the relative duration of
diastole, and Corrigan reasoned that a rapid
rate would be advantageous to a patient with
aortic regurgitation:
"If the action of the heart be rendered very
slow, the pause after each contraction will be
long, and consequently the regurgitation of
blood must be considerable. Frequent action
of the heart, on the contrary, makes the pause
after each contraction short; and in proportion as the pauses are shortened, the regurgitation must be lessened. Instead, then, of regarding an increase of frequency in the action
of the heart as an aggravation of the disease, it
must be viewed, as we have already viewed
hypertrophy of the heart, as a provision for
remedying as far as possible the evil consequences arising from inadequate valves."
'
From the Clinic of Surgery, National Heart Institute, Bethesda, Maryland.
32
Circulation, Volume XXXV, January 1967
DETERMINATIONS OF AORTIC BLOOD FLOW
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The impression that a rapid heart rate
diminishes the severity of aortic regurgitation seems to have been generally accepted by
physicians since Corrigan's time, and this concept has been supported by modern clinical
and laboratory investigations.1 3 It is now
possible, however, to measure directly the
magnitudes of forward and regurgitant aortic
flow in man, and in the present studies, the
relations of heart rate to the severity of aortic
regurgitation were determined at the time of
operation in patients with severe aortic regurgitation. In certain patients, left ventricular
function was also assessed by increasing the
ventricular preload or afterload, and the effects of administration of isoproterenol were
determined when the heart rate was constant
and when it was allowed to increase.
Methods
Nine adult patients were studied in the course
of operative replacement of the aortic valve. All
were in functional class III or IV and, on the
basis of their symptoms and the clinical and
hemodynamic findings, operative treatment of the
aortic valve lesion was indicated. Each patient
was studied by right and left heart catheterization preoperatively, and in six patients the results of the studies indicated isolated, severe aortic
regurgitation without associated aortic stenosis.
The other three patients (R.O., A.A., and L.S.)
also had severe aortic regurgitation, but associated
outflow obstruction was indicated by peak systolic pressure gradients across the aortic valves
of 20, 65, and 62 mm Hg, respectively. In patient A.Z., no pressure gradient across the aortic
valve was recorded at preoperative cardiac catheterization, but a peak systolic gradient of 20 mm
Hg was present at the time of operative study.
In every patient arterial indicator-dilution curves,
recorded after injections into the left ventricle,
demonstrated prolonged descending limbs, characteristic of valvular regurgitation. In eight of the
nine patients, aortic regurgitation was also demonstrated by angiocardiograms made after injections of contrast medium into the ascending aorta. In patient A.A., mild mitral regurgitation was
evident at cineangiocardiography, but the mitral
valve was considered normal in the other patients.
The general operative methods utilized for aortic valve replacement were similar in all patients.
Anesthesia was induced with sodium thiopental
or halothane and maintained with nitrous oxide,
oxygen, and halothane in a concentration of 0.2
Cifrculation, Volume XXXV, January 1967
33
to 0.5%. The heart was exposed through complete median sternotomy, and the hinged transducer of a sine-wave electromagnetic flowmeter
(Medicon K-2004) was placed around the ascending aorta immediately below the origin of
the innominate artery. A transducer with a
lumen 5 to 6 mm less than the measured diameter of the aorta was utilized to ensure a snug
fit. The flow transducer was calibrated at the conclusion of each study by methods previously described in detail.5
Observations were made immediately prior to
the institution of cardiopulmonary bypass. Pressures were measured in the ascending aorta and
left ventricle by means of 20-gauge needles attached to Statham P23Db pressure transducers
through rigid saline-filled nylon connecting tubes
(1.7 mm, I.D.). The pressure pulses, the electrocardiogram, and the instantaneous aortic flow pattern were recorded simultaneously on magnetic
tape, and subsequently reproduced with a photographic recorder operated at various paper speeds.
When the effects of altered blood volume were
studied, the patient was heparinized, and connections to the heart-lung machine were made
through cannulae in the right atrium and femoral
artery. Zero flow was determined in each study
shortly after the initiation of bypass. The aorta
was occluded at the base of the heart, proximal
to the flow transducer, by a clamp placed
through the transverse sinus of the pericardium.
This proximal site of occlusion prevented distortion of the aortic segment within the flow transducer and minimized any effects that the metallic
clamp might have on the electromagnetic field of
the transducer.
Observations of Instantaneous Aortic Blood
Flow, Left Ventricular Pressure, and Central
Aortic Pressure
These were made under control conditions,
and after the following interventions:
Alterations in Heart Rate
The heart rate was controlled and increased by
electrical stimulation of the right atrium or right
ventricle in six patients. After each change in
rate, a 2 to 3-minute stabilization period was
allowed before subsequent observations were recorded. In three patients, neostigmine (0.5 or
1.0 mg) was administered intravenously prior to
the study period so that rates slower than the
spontaneous one could be investigated.
Intravenous Administration of Isoproterenol
Patient A.Z. received 3.0 ,ug of isoproterenol
as a single intravenous injection and the heart
rate was not controlled. Patient A.A. was given
2.0 ,ug of isoproterenol intravenously, and observations were continuously made while the heart
34
rate was held constant at 90 beats per minute by
means of ventricular pacing. In patient D.G.S.,
isoproterenol was given as a constant infusion
(2.0 ,tg/min), and the heart rate was not controlled.
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Alterations in Left Ventricular Preload or Afterload
Observations were made in patient D.S. after
partial constriction of the ascending aorta with a
vascular clamp placed distal to the flowmeter
transducer and aortic pressure catheter. In patients L.S. and J.L., the blood volume was increased 1,000 cc by infusions of blood from the
heart-lung machine into the femoral artery. Recordings were made 2 to 3 minutes after each
stepwise change in blood volume in order to allow
stabilization. In patient J.L. the heart rate was
held constant during the study.
Calculations
From the records of instantaneous aortic flow,
total left ventricular stroke volume (cc) was
determined by planimetric integration of the area
under the flow curve during the systolic ejection
period, that is, the total area above the line
of zero flow. Regurgitant flow during the succeeding diastolic period (regurgitant volume per
stroke, cc) was similarly measured by determination of the area below the line of zero flow. Net
forward stroke volume (cc) was obtained by
subtracting the regurgitant volume from the total
stroke volume. The per cent regurgitation was
calculated by multiplying the ratio of the regurgitant volume per stroke to the total stroke
volume by 100. Peak forward flow and peak regurgitant flow were also measured. Total forward flow (cc/min), regurgitant flow (cc/min),
and net forward flow (cc/min) were obtained by
multiplying the various stroke volumes by the
heart rate.
The duration of systole (sec) was defined as
the measured duration of the systolic ejection period as indicated in the flow tracing. The remainder
of the cardiac cycle, defined here as diastole
(sec), was the time from the beginning of regurgitant flow until the onset of the succeeding
systolic ejection period; this interval included the
very brief time required for isometric contraction,
for which no correction was made. Systolic seconds per minute were obtained by multiplying
the duration of systole by the heart rate, and
diastolic seconds per minute by multiplying the
duration of diastole by the heart rate. Dividing
the total forward flow per minute by the systolic
seconds per minute yielded total forward flow
per systolic second (cc/sec); similarly, division
of regurgitant flow per minute by the diastolic
seconds per minute gave regurgitant flow per diastolic second.
BRAWLEY, MORROW
From the records of left ventricular and aortic
pressure, the following variables were measured
or calculated, and expressed in mm Hg: (1) left
ventricular peak, systolic, and end-diastolic pressures; (2) aortic peak, mean, diastolic, and pulse
pressures; (3) when present, peak and mean systolic gradients across the aortic valve; and (4)
mean pressure gradient between the aorta and left
ventricle during diastole (by planimetry of the
area between the pressure curves).
The following variables were calculated by relating flow and pressure: (1) area of the regurgitant orifice and of the stenotic orifice (cm2),
when present, according to the Gorlin formulael'
(2) left ventricular pressure work6 (g-m/stroke);
(3) left ventricular kinetic work7 (g-m/stroke);
(4) total left ventricular work, the sum of pressure
and kinetic work. Minute work was determined by
multiplying stroke work by the heart rate. In calculating left ventricular kinetic work, the effective
area of the stenotic valve orifice, if present, was
utilized in determining the velocity of flow; if a
pressure gradient across the aortic valve was not
present, the inner diameter of the flowmeter transducer minus twice the estimated aortic wall thickness was used in this determination.6 All measurements of pressure and flow presented are averages
obtained by analysis of three or more cardiac cycles. It should be noted that in the flow measurements coronary flow could not be distinguished
from regurgitant flow through the valve, but coronary flow would have represented only a small
fraction of the measured regurgitant volume under
any circumstances. Also, no correction was made
in the pressure records for the very small delay
in the transmission of the pressure pulses from
the heart to the transducers.
Results
Alterations in Heart Rate
The hemodynamic observations made at
various heart rates in four patients with aortic regurgitation, and in two patients with
combined aortic regurgitation and aortic stenosis, are summarized in table 1, and representative records of pressure and aortic flow
at different heart rates are reproduced in
figures 1 and 2.
As the heart rate was increased, total left
ventricular stroke volume, regurgitant volume
per stroke, and net forward stroke volume
decreased progressively in all patients. The
various flows measured in patient A.A. at
rates of 51 to 143 beats/min are plotted in
figure 3A as stroke volumes, and in figure 3B
as minute volumes. Although all three stroke
Circldation, Volume XXXV, January 1967
35
DETERMINATIONS OF AORTIC BLOOD FLOW
PRE-OP.
PRE-OP
55% REGURCX
H.R.z51
IH.R.-69
t
750
o5001-
uX
75%REGURG.
7
1
t33ccr
HRR.92
65%REGURG
407cc
250
RR-143 65V/.EGURG
345°°r
0
6
rCC.2
1--250[
-250
(-7) 00cc
-170cc
IR.98
55%
55%
H.R.'143
+500A
+148cc
81cc
25
250 50-
89c
5
)4Xccl
I
1)30cc
>
-)49cc
Wt
t
(-)42cc
150 100-
Li1
Ao.sec
5Q -
Recods o
Figure 1
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Records of instantaneous ascending aortic blood flow,
left ventricular (LV) and central aortic (Ao) pressure obtained at three diferent heart rates in patient F.E. Total forward stroke volume is indicated
by the stippled area above the line of zero flow,
and regurgitant volume per stroke by the crosshatched area below the line of zero flow. With the
initial increase in heart rate from 69 to 92 beats!
min, the total forward stroke volume decreased from
133 to 107 cc, but the regurgitant volume per stroke
decreased relatively more and the per cent regurgitation fell slightly. As the heart rate was further
increased to 143 beats/min, total forward and
regurgitant stroke volumes decreased proportionately
and the per cent regurgitation remained unchanged.
Apparent in the pressure records is a progressive
increase in the mean aortic pressure, a decrease in
the aortic pulse pressure, and progressive abbreviation
of the duration of diastole.
intantne%re 2u
Recors
ofinstatan
d
ausartic bodflow, left ven-
tricular (LV) and central aortic (Ao) pressure obtained at increasing heart rates in patient A.A., who
had severe aortic regurgitation combined with aortic
stenosis. As the heart rate was increased fromS1 to
143 beats/mm,n the decrease in total forward stroke
volume wvas accompanied by a porportional decrease
in the regurgitant volume per stroke, and the
per cent regurgitation remainred unchanged. The calculated area of the stenotic orifice remAined constant,
as did the calculated area of the regurgitant orifice
in the aortic valre.
solumes fell as rate increased, the per cent
regurgitation remained almost constant. The
total forward, regurgitant, and net forward
blood flows per ute in this patient varied
less, but all were greatest at a rate of 90
beats/min. The total forward flows and regurgitant flows measured over a wide range
9
rotal Forrod F/ow
8
7
- R-g,rgiaof
4
F/-
A/el ForwrdF
Ur
o0
8
A
50
Figure 3
Total forward flow, regurgitant flow, and net forward
60
70
80
90
100
110
HEART RATE
120
130
flow, recorded in patient A.A. at heart
beats/min. (A) The data are plotted as volumes per stroke,
(B) The data are plotted as volumes per minute. All volumes per stroke decreased progressively as the heart rate was increased, but the per cent regurgitation remained essentially
unchanged throughout the range of heart rates. The forward and regurgitant flows per minute
also changed little, but total forward flow and net forward flow were greatest at a rate of 90,
rate apparently optimal for the maintenance of the peripheral circulation in this patient.
rates between 51 and 143
a
Circulation, Volume XXXV, January 1967
140
150
36
BRAWLEY, MORROW
Table 1
Hemodynanic Observations Made at Various Heart Rates in Four Patients with Pure Aortic Regurgitation and
Patient
and
body surface
area (M2)
A.A.
1.9
R.O.
2.0
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J.L.
2.0
F.E.
1.5
E.V.
1.9
D.S.
2.0
Total
Heart rate
(beats / min)
forward flow
(L./ min)
51
60
69
90
98
118
143
52
53
57
71
90
109
128
146
83
99
117
133
154
69
73
83
92
105
118
128
136
143
68
88
109
125
146
171
67
80
98
115
7.55
8.28
8.21
9.18
8.72
8.73
7.87
9.00
8.64
9.13
9.73
9.72
9.92
9.22
7.59
16.35
16.24
15.33
13.17
9.24
9.18
9.71
10.29
9.84
9.56
9.56
8.70
8.43
9.29
14.96
17.51
16.02
15.38
13.87
11.29
7.17
7.28
7.25
6.68
Regurgitant
flow
(L / min)
Net forward
flow
(L / min)
4.13
4.14
4.83
4.95
4.80
4.72
4.29
3.42
4.14
3.38
4.23
3.92
4.01
3.58
4.22
4.29
3.71
4.40
4.68
6.00
5.38
4.23
3.15
4.85
4.45
2.26
1.69
2.28
2.85
3.98
3.40
2.73
3.31
2.94
2.72
3.28
3.54
4.93
1.52
0.50
1.02
1.71
3.48
3.68
3.53
3.34
4.78
4.35
5.42
5.33
5.04
3.92
3.84
3.36
13.20
11.39
10.88
10.91
7.55
6.90
6.86
6.31
6.44
6.83
6.25
5.76
5.71
6.01
11.42
12.58
14.50
14.88
12.85
9.58
3.69
3.60
3.72
3.34
of heart rates in all six patients studied are
shown in figure 4. In four of the patients,
total forward and regurgitant flows per minute
changed relatively little as the heart rate was
increased, but two patients evidenced precipitous drops in both total forward and regurgitant flow at heart rates above 120 beats/
min. Generally, total forward flow, regurgitant flow, and net forward flow were maximal
Peak
%
Regurgitation
Peak forward
flow
(cc / sec)
55
50
59
54
55
54
55
53
50
59
55
52
40
42
44
81
70
71
83
82
75
71
61
65
71
66
66
68
65
76
72
90
97
93
85
51
50
51
50
594
572
572
530
509
487
404
817
817
785
753
718
622
557
458
1040
1040
932
822
548
614
614
581
549
517
453
453
420
420
1050
1080
980
980
875
660
482
448
413
344
regurgitant
flow
(cclsec)
233
233
212
233
212
212
212
164
164
164
164
164
131
131
131
493
438
438
383
274
226
226
226
226
258
258
258
258
258
595
560
630
630
525
385
206
189
189
155
and
heart rate between 80 and 110 beats/min,
were least at either the highest or lowest
rate
observed. With increasing
at
a
heart rate,
the
magnitude of peak forward flow fell in every
patient, but the changes in peak regurgitant
flow were variable (table 1).
The effects of heart rate on the per cent
regurgitation, the ratio of regurgitant flow to
total forward flow, are included in table 1,
Circulation, Volune XXXV, January 1967
DETERMINATIONS OF AORTIC BLOOD FLOW
37
Two with Combined Aortic Stenosis and Regurgitation
Systemic
arterial
pressure,
S / D, mean
(mm. Hg)
LVED
pressure
(mm. Hg)
Downloaded from http://circ.ahajournals.org/ by guest on April 30, 2017
117/35, 57
119/37, 60
101/40, 62
106/46, 69
99/48, 68
95/51, 68
77/53, 69
135/42, 78
149/38, 76
145/42, 86
147/50, 84
122/51, 86
122/59, 82
101/59, 84
90/56, 78
90/41, 71
93/50, 71
86/54, 69
78/45, 65
60/30, 50
114/47, 77
115/50, 80
114/47, 82
116/52, 85
114/56, 87
110/62, 86
105/65, 83
102/67, 81
102/69, 84
117/44, 75
150/55, 93
123/64, 92
114/68, 94
110/70,
92/53,
100/46,
92/52,
92/52,
90/50,
and
are
Mean
diastolic
Ao-LV
gradient
(mm. Hg)
21
27
30
34
35
35
30
45
49
49
56
52
52
52
45
42
42
42
33
22
46
49
47
49
52
53
33
35
26
22
22
20
15
21
15
16
14
12
15
15
16
18
13
11
12
10
15
15
13
13
13
13
11
9
9
50
49
51
47
57
56
56
42
26
46
47
45
38
24
20
22
22
18
17
85
71
68
70
10
8
8
74
66
Area effective
regurgitant
orifice (cm2)
12
0.51
0.47
0.53
0.55
0.53
0.54
0.56
0.37
0.33
0.41
0.41
0.40
0.34
0.36
0.35
1.22
1.10
1.11
1.29
1.06
0.59
0.58
0.56
0.57
0.61
0.59
0.57
0.59
0.60
0.94
0.98
1.21
1.27
1.32
1.24
0.31
0.31
0.36
0.36
summarized in figure 5. The determay be
minants of the per cent regurgitation
related in the following manner:
% Regurgitation
Regurgitant
(cc/min)
Total forward flow (cc/min)
flow
-
Regurgitant flow (cc)
Diastolic sec
Total forward flow (cc)
Systolic sec
Diastolic sec
Minute
Systolic sec
x
Circulation, Volume XXXV, January 1967
Minute
Total forward
flow per
systolic sec
(cc)
377
363
360
366
342
322
275
529
508
515
472
450
395
343
274
727
655
592
495
353
429
443
424
412
379
353
309
295
325
726
796
668
615
527
439
343
325
284
252
IMean
Regurgitant
flow per
diastolic sec
(cc)
systolic
LV-Ao
gradient
(mm. Hg)
104
62
58
61
54
52
45
33
32
27
32
31
30
23
20
18
111
130
141
140
143
137
111
101
128
135
130
112
116
105
353
Area effective
stenotic
orifice (cm2)
1.08
1.07
1.04
1.10
1.07
1.08
1.08
2.06
2.20
2.04
1.90
1.84
1.86
1.71
1.43
320
320
328
223
179
181
180
179
197
190
180
183
190
290
332
403
425
382
280
94
96
109
100
The four factors in the final equation above
calculated for each heart rate in the six
patients, and the durations of systolic ejection and of diastole, in seconds per minute, at
all heart rates in all six patients are plotted in
figure 6. Systolic seconds per minute increased
from 17 to 20 at a rate of 51 beats/min to
26 to 29 at a rate of 146 beats/min; diastolic
seconds per minute decreased from 43 to 40
were
BRAWLEY, MORROW
38
21
r
18r
18
w.
15
5
C.'
s 12
o 12
8
0
L9 9
U
<9
r
z
' 6
13 6
0
0
lr 3
3
U
2U
I'- A,
I 11
4U
IP
bU
A
8U A,r
HEART RATE
IOU
12U
1
I
14U
A
16
-
|
t
o
180_.
I
20
B
40
60
80
100
120
HEART RATE
140
180
160
Figure 4
Downloaded from http://circ.ahajournals.org/ by guest on April 30, 2017
Total forward flow and regurgitant flow per minute, measured in all patients at all heart rates
studied. In four patients, total forward flow (A) and total regurgitant flow (B) changed
relatively little as the heart rate was increased. Two patients, however, evidenced precipitous
falls in both forward and regurgitant flow per minute at rates greater than 120 beats/mim.
0
OOF
60r_
80
50
, 60 )
0
40
cn 40
a.0
i
a
-&
a
*
:,
30
a-
*
a'
40
It.*s
:. It
I
20t
20.-
*
I0
20
40
60
80
100
120
HEART RATE
140
160
180
Li
J
10 -
0
Figure
5
Per cent regurgitation measured at all heart rates in
each of the six patients studied.
U
0
40
i
60
80
100
120
140
HEART RATE
160
180
200
Figure 6
to 34 to 31 over this same range of heart rates.
Expressed in other terms, the duration of diastole was twice that of systole at the lowest
rates, while systole and diastole were of almost equal duration at the highest rates. Total forward flow per systolic second, the mean
rate of systolic ejection, diminished consistently and progressively in each patient as the
heart rate was increased (fig. 7). Regurgitant
flow per diastolic second, however, remained
virtually constant in four of the six patients
and was variable in the other two (fig. 8).
In summary, with progressive increases in
heart rate, the duration of diastole per minute
decreased, while the duration of systole per
minute increased; with this change in the
The durations of diastole and of systole measured at
all heart rates in six patients. At the lowest rates,
the duration of diastole is approximately twice that
of systole, while at faster rates they become of almost
equal absolute duration.
systolic-diastolic time ratio a decrease in per
cent regurgitation would be anticipated. This
did not occur, however, because the rate of
systolic ejection declined markedly, while the
rate of regurgitant flow remained relatively
constant. Thus, as the heart rate was increased,
the per cent regurgitation changed little, since
it tended to be diminished by the changes in
the durations of systole and diastole, and to
be augmented by the alterations in flow.
Circulation, Volurne XXXV,
January
1967
DETERMINATIONS OF AORTIC BLOOD FLOW
39
I00°1
500r
0
9qoo
400
0
Eo
{, 800
a
w
-
300
Q
,,,0 700
o
O 6CC
3
r
mm-
En
-
200
_
22Zz.
z
HEr
D)
0
500
L4I
C
oo
-)II
80
60
100
40
0
° 700
c]
03 300
H
140
160
180
Figure 8
Mean rates of regurgitant blood flow in aU six
tients at all heart rates studied. In contrast to
changes in the rate of forward flow (fig. 7),
rate of regurgitant flow remained virtually
changed in four patients, and was variable in
r2200
H
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I10ok
40
_
120
HEART RATE
60
1I,
1
L}-I
80
120
140
100
HEART RATE
160
180
pa-
the
the
un-
the
other two.
200
Figure 7
A progressive decrease in the rate of systolic ejection
occurred in every patient as the heart rate increased.
Relations of heart rate to the nwean rates of systolic
ejection in all six patients at all heart rates studied.
Table 2
Relations of Heart Rate to the Various Components of Calculated Left Ventricular Work in Two Patients
with Pure Aortic Regurgitation (F.E. and J.L.) and One with Combined Aortic Stenosis and Regurgitation
(R.O.)
Patient
and
body surface
area
(i2)
F.E.
1.5
J.L.
2.0
R.O.
2.0
Heart rate
(beats / min)
LV pressure
Work per minute
Stroke work
(g-ml stroke m2)
69
73
83
92
105
118
128
136
143
83
99
117
133
154
52
53
57
71
90
109
128
146
Circulation, Volume XXXV, January 1967
111
115
109
97
82
65
53
48
53
87
81
63
39
17
124
129
132
115
82
62
43
28
(kg-i! mi/inM2)
7.7
8.4
9.0
8.9
8.6
7.7
6.7
6.5
7.5
7.2
8.1
7.3
5.1
2.9
6.4
6.8
7.5
8.2
7.4
6.7
5.5
4.0
LV work
Kinetic stroke Kinetic per minute
(g-m/stroke!M2) (kg-m/min/m2)
13
15
13
10
7
5
3
3
4
24
16
11
5
2
30
29
28
23
18
11
8
5
0.9
1.1
1.1
0.9
0.8
0.6
0.4
0.5
O.5
2.0
1.6
1.3
0.7
0.3
1.6
1.3
1.6
1.7
1.6
1.2
1.0
0.8
Total per minute
(kg-mi min/m2)
8.6
9.5
10.1
9.8
9.4
8.3
7.1
7.0
7.0
9.2
9.7
8.6
5.8
3.2
8.0
8.1
9.1
9.9
9.0
7.9
6.5
4.8
40
BRAWLEY, MORROW
Table 3
The Hemodynamric Effects of Isoproterenol Administration in Two Patients with Combined Aortic Stenosis and
Patient
and
body surface
area
(i2)
A.A.
19
A.Z.
1.8
D.G.
1.6
Status
Control
After 2 ,ug
isoproterenol
Control
After 3 A g
isoproterenol
Control
During
isoproterenol
infusion
Heart rate
(beats / min)
Total
Regurgitant
forward flow
flow
/
(L!min)
(L I min)
Peak
Net forward
Peak forward regurgitant
flow
flow
%
flow
(L / min) Regurgitation (cc I'sec)
(cc I sec)
90
90
77
94
91
9.18
9.54
9.93
11.47
8.19
4.95
4.95
8.54
8.55
5.00
4.59
1.39
2.92
3.19
54
52
86
75
61
530
658
666
777
756
233
212
333
333
210
109
9.37
4.36
5.01
47
860
148
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Left ventricular end-diastolic pressure and
aortic pulse pressure were always higher at
the lower heart rates; mean aortic pressure,
if it changed appreciably, was lower at either
end of the range of heart rates studied. The
calculated area of the effective regurgitant
orifice did not remain constant during alterations of heart rate, but varied less than 0.1
cm2 in four of the six patients. In patients J.L.
and E.V., respectively, maximum changes of
0.23 and 0.43 cm2 were observed.
The influences of heart rate on the calculated work of the left ventricle in three of the
patients are presented in table 2. Total left
ventricular work per minute was elevated
(>5.5 kg-m/min/m2) at every rate in each
patient, except at the very highest rates in
patients J.L. and R.O., in whom both pressure
and flow fell strikingly. A marked decrease in
stroke work, both pressure and kinetic, occurred as the heart rate was increased, and as
the stroke volume fell. Since left ventricular
kinetic stroke work varies as the third power
of the stroke volume, it declined more strikingly than pressure stroke work as the heart
rate increased. Minute kinetic work was also
appreciably reduced at the faster heart rates
because of this relationship to stroke volume.
Isoproterenol Administration
The hemodynamic changes which were observed in three patients following administration of isoproterenol are presented in table 3.
In all, positive inotropic effects were evident,
4.23
the left ventricular end-diastolic pressure decreased, and the rate of systolic ejection became significantly faster. In patients A.Z. and
D.G., the heart rates increased approximately
20 beats/min; total forward flow per systolic
second increased, but regurgitant flow per
diastolic second changed little. Also, even
though the duration of each ejection was less,
the faster heart rate resulted in an increase
in the systolic seconds per minute, and a decrease in the diastolic seconds per minute.
This combination of changes in flow and in
the durations of systole and diastole resulted
in striking increases in total forward flow and
net forward flow per minute, and a reduction
in the per cent regurgitation.
In patient A.A., the heart rate was maintained constant during the administration of a
single dose of 2.0 /g of isoproterenol. Forward and regurgitant flows per beat and per
minute did not change, although the duration of ejection was shorter. WVith a constant
heart rate, therefore, isoproterenol resulted in
no significant change in the per cent regurgitation.
Alterations in Left Ventricular Preload
Afterload
or
The changes in flow and pressure resulting
from these interventions are summarized in
table 4. In patient D.S., the aorta was gradually constricted with a vascular clamp distal
to the flow transducer and the site at which
aortic pressure was measured. The heart rate
Circulation, Volume XXXV, January 1967
41
DETERMINATIONS OF AORTIC BLOOD FLOW
Regurgitation, and One with Pure Aortic Regurgitation
Total
forward Regurgitant
flow per
flow per
systolic sec diastolic sec
(cc)
(cc)
LVED
pressure
(mm Hg)
Mean
diastolic
Ao-LV
gradient
(mm Hg)
Area effective
regurgitant
orifice (cm2)
69
54
77
84
74
22
34
0.55
367
15
9
3
11
32
52
61
53
0.53
0.68
0.64
0.36
143/57, 88
9
60
0.30
Systemic
arterial
pressure,
S/ D, mean
(mm Hg)
106/46,
79/40,
119/44,
128/55,
110/48,
Systolic sec
per minute
Diastolic sec
per minute
141
25.0
411
479
531
476
135
217
223
117
23.2
20.7
21.6
17.2
35.0
36.8
39.3
38.4
42.8
535
102
17.5
42.5
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was controlled at 80 beats/min. As the aorta
was constricted, the aortic systolic pressure
proximal to the clamp rose from 96 to 126
mm Hg, but the aortic diastolic pressure fell
from 52 to 26 mm Hg. Since the left ventricular end-diastolic pressure rose little, the calculated mean diastolic pressure gradient across
the valve fell strikingly. With these changes
in pressure, total forward flow decreased
markedly. Regurgitant flow, however, decreased less, and the net result was an increased per cent regurgitation. The increased
resistance to ejection increased the duration
of systole and shortened diastole, but this otherwise favorable change in durations was offset by the fact that forward flow per systolic
second fell much more than regurgitant flow
per diastolic second.
In patient L.S., in whom the heart rate was
not controlled, the first infusion of 500 cc of
blood increased the aortic systolic, diastolic,
and mean pressures, and the left ventricular
end-diastolic pressure. Both total forward
and regurgitant flows increased proportionally, and the per cent regurgitation remained
unchanged. Different effects were noted after
the second infusion, however, since further
rises in aortic and left ventricular end-diastolic pressure were accompanied by a decrease in total forward flow and the rate of
forward flow, and increases in regurgitant
flow and in the per cent regurgitation. With
each infusion, the relative duration of systole
increased and that of diastole decreased,
Circzslation, Volume XXXV, January 1967
Mean
systolic
LV-Ao
gradient
(mm Hg)
Area effective
stenotic
orifice (cm2)
54
74
35
45
1.10
1.07
1.82
1.79
changes attributable to the faster heart rate.
In spite of the altered durations of systole
and diastole the per cent regurgitation increased from 34 to 41.
In patient J.L., the heart rate was constant.
Each infusion of 500 cc increased aortic and
left ventricular end-diastolic pressure, but total forward, regurgitant, and net forward
flows, which rose with the first infusion, all
decreased slightly with the second.
In both patients whether heart rate was constant or not, each infusion raised the left
ventricular end-diastolic pressure. After the
first infusion, total forward flow did not rise
appropriately, and after the second, it decreased. Thus, after the second infusion the
ventricles of both patients were apparently
operating on the descending limbs of their
respective ventricular function curves. In patient L.S., the functional impairment was
more severe, and after the second infusion
there was an increase in regurgitant flow and
in the per cent regurgitation.
Discussion
An understanding of the complex hemodynamic changes which accompany incompetency of the aortic valve is facilitated by an
initial consideration of the effects of acute
aortic regurgitation. Immediately following
the experimental production of an aortic valve
defect, the total forward stroke volume increases slightly, and the net forward stroke
volume decreases; the magnitude of these
42
BRAWLEY, MORROW
Table 4
Hemodynamic Effects of Increased Left Ventricular Afterload or Preload in Two Patients with Pure Aortic
Patient
and
l)ody surface
area (in2)
D.S.
2.0
Status
Control
Mild aortic
constriction
Moderate
Heart rate
(beats / min)
Total
forward flow
(L min)
Regurgitant
flow
(L / min)
Net forward
flow
(L / min)
%
Regurgitation
80
80
7.04
4.64
4.00
3.28
3.04
1.36
57
71
80
3.24
2.35
0.89
72
69
7.18
2.35
4.83
33
70
78
88
7.42
7.18
17.86
2.52
2.96
10.56
4.90
4.22
7.30
34
41
89
89
18.07
17.53
10.68
10.24
7.39
7.29
59
58
aortic
constriction
L.S.
1.6
J.L.
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2.0
Control
blood volume
+ 500 cc of blood
+ 1000 cc of blood
Control
blood volume
+ 500 cc of blood
+ 1000 cc of blood
changes is principally determined by the
volume of blood regurgitated through the incompetent valve during diastole.8-13 Simultaneously, left ventricular end-diastolic pressure rises and the mean and diastolic aortic
pressures fall. The heart rate also increases,
but in spite of this the net result and the principal acute effect are decreases in effective
systemic blood flow and mean perfusion pressure; the magnitude of these decreases
depends primarily upon the size of the regurgitant orifice created. With chronic experimental aortic regurgitation, however, net forward
stroke volume and effective systemic blood
flow have been found to be normal, and the
total forward and regurgitant flows are much
larger than those measured immedately following the production of the lesion.14 Also, in
dogs with chronic aortic regurgitation, the
mean systemic arterial pressure returns toward normal, but the aortic pulse pressure and
frequently the left ventricular end-diastolic
pressure remain high.
Observations in patients with clinical evidences of severe aortic regurgitation have
demonstrated abnormalities of flow and pressure similar in many respects to those which
occur in animals with chronic lesions.5 15 In
man, however, the proportion of the stroke
volume regurgitated has been found to be as
59
high as 80%, while regurgitant flows more
than 35 to 40% of total forward flow are usually incompatible with long-term survival in
dogs.51 This difference is explained by the
fact that the onset and progression of regurgitation in man are gradual, except in those
rare instances when the valve is damaged by
trauma or acute infection. In animals, on
the other hand,-it is necessary to produce a
valvular defect small enough to be tolerated
acutely, and the orifice does not change significantly thereafter. Both clinical and experimental studies indicate, however, that the left
ventricle compensates for aortic regurgitant
flow by increases in total forward stroke volume and end-diastolic volume and pressure9' 16 and that the increased energy required for this compensation is reflected in
the abnormally high levels of left ventricular
work calculated in these and other patients.5
In the six patients in whom heart rate was
altered, no consistent decrease in the per cent
regurgitation occurred as the rate was increased. Such a finding was predicted by
Wiggers, 17 18 from analyses of left ventricular and aortic pressure records in dogs with
aortic regurgitation. He concluded that
abridgement of diastole, as a consequence
of increased rate, would have little effect on
the severity of regurgitation, since only the
Circulation, Volume XXXV, January 1967
DETERMINATIONS OF AORTIC BLOOD FLOW
43
Regurgitation, and One (L.S.) with Combined Aortic Stenosis and Regurgitation
Systemic
arterial
pressure,
S / D, mean
(mm Hg)
LVED
pressure
(mm Hg)
Mean
diastolic
Ao-LV gradient
(mm Hg)
96/52, 74
124/38, 72
8
10
48
23
126/26, 68
12
101/43, 71
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Total forward
flow per
systolic sec
(cc)
Regurgitant
flow per
diastolic sec
(cc)
0.34
0.48
314
170
12
0.52
21
43
114/49, 77
125/58, 82
93/49, 69
39
43
24
105/56, 78
99/54, 80
31
32
Area effective
regurgitant
orifice (cm2)
Systolic sec
per minute
Diastolic sec
per minute
106
100
22.4
27.2
37.6
32.8
111
76
29.2
30.8
0.23
289
67
24.8
35.2
33
30
42
0.29
0.36
1.04
294
271
723
72
88
299
25.2
26.5
24.7
34.8
33.5
35.3
40
39
1.07
1.07
747
701
298
292
24.2
25.0
35.8
35.0
last part of diastole, in which least regurgitant flow occurred, would be eliminated. Direct measurements of aortic flow were made
in this laboratory by Weldon and Cooper,13
and they also demonstrated a relatively constant regurgitant ratio during alterations of
heart rate in dogs with experimental aortic
regurgitation.'3
As the heart rate of the normal subject is
increased by the administration of atropine or
by electrical stimulation, the cardiac output
remains constant over a fairly wide range of
heart rates, since the stroke volume progressively decreases.91-21 The output falls, however, when the rate is either extremely rapid
or slow. The maximum stroke volume of
which the left ventricle is capable determines
the limit to which the heart rate can be
slowed without depressing cardiac output,
and the rate may be increased without a diminution in output until the duration of diastolic
ventricular filling is reduced below a critical
point.22 Similar relationships were noted in
the patients with aortic regurgitation; total
forward flow per minute changed little except
at extremes of heart rate. The responses
which occur when the heart rate increases during muscular exercise, however, are quite
different. Under these circumstances, positive
inotropic effects act to maintain or increase
Circulation, Volume XXXV, January 1967
the stroke volume, and the cardiac output
rises.23 The administration of isoproterenol
produces hemodynamic responses similar to
those which occur during exercise: tachycardia, reduced peripheral vascular resistance,
improved myocardial contractility, and an increase in cardiac output.24 In the present
studies the increased rate after isoproterenol
was accompanied by an increase in total forward flow, since the stroke volume did not
fall. Also, the per cent regurgitation was reduced at the higher heart rate, a combined
result of decreased diastolic time and increased rate of systolic ejection. These observations suggest that the per cent regurgitation may diminish during exercise if the left
ventricle has sufficient functional reserve to
provide the increased forward flow which is
necessary.
The interventions designed to alter the left
ventricular preload or afterload were carried
out to obtain information concerning the extent to which the function of the left ventricle
is altered by severe and long-standing aortic
regurgitation. In the two patients in whom the
blood volume was increased, substantial increases in left ventricular end-diastolic pressure occurred, but neither patient had an
increase in total forward flow. Similarly, in
the patient in whom the aorta was constricted,
BRAWLEY, MORROW
44
Downloaded from http://circ.ahajournals.org/ by guest on April 30, 2017
total forward flow progressively diminished as
the end-diastolic pressure increased. In all
three patients, whether or not the heart rate
was constant, the mean rate of ejection also
fell. Thus, in each patient the observations
indicated that the left ventricle was operating
at or near its functional limit, and with either
an increased flow or pressure load its performance deteriorated. The important question as to whether irreversible impairment of
left ventricular performance occurs in patients
with chronic aortic regurgitation cannot yet
be answered with certainty. Initial studies,
however, carried out a number of months
following prosthetic replacement of the incompetent valve, indicate that in many patients normal or near-normal function is re-
10.
11.
12.
13.
14.
stored.25
References
1. GORLIN, R., MCMILLAN, I. K. R., MEDD, W. E..
MATTHEWS, M. B., AND DALEY, R.: Dynamics of the circulation in aortic valvular disease.
Amer J Med 18: 855, 1955.
2. CORRIGAN, D. J.: On permanent patency of the
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3. XVARNER, H. R., AND TORONTO, A. F.: Effect of
heart rate on aortic insufficiency. Fed Proc
19: 120, 1960.
4. MALOOLY,
H. W.,
5.
6.
7.
8.
D.
AND
A., DONALD, D. E., MARSHALL,
WOOD, E. H.: Combined flow-
meter-dye dilution study of the acute effects
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on the degree of experimental aortic regurgitation. Physiologist 4: 70, 1961.
MoRRow, A. G., BRAWLEY, R. K., AND BRAUNWALD, E.: Effects of aortic regurgitation on
left ventricular performance: Direct determinations of aortic blood flow before and after
valve replacement. Circulation 31 (suppl. I):
1-80, 1965.
PIERCE, G. E., MORROW, A. G., AND BRAUNWALD,
E.: Idiopathic hypertrophic subaortic stenosis:
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of obstruction and its hemodynamic consequences. Circulation 30 (suppl. IV): IV-152,
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MITCHELL, J. H., XVALLACE, A. G., AND SKINNER, N. S., JR.: Intrinsic effects of heart rate
on left ventricular performance. Amer J Physiol 2051 41, 1963.
NEWMAN, M. M., BAY, E. B., KOLIN, A., AND
ADAMS, WV. E.: Electromagnetic measurement
of aortic blood flow in the presence of artificial
aortic insufficiency. Surg Forum 1: 304, 1950.
AND SARNOFF,
S. J.: Hemodynamic effects of quantitatively
varied experimental aortic regurgitation. Circulation Research 5: 546, 1957.
SCHENK, W. G., JR., PORTIN, B. A., LESLIE,
M. B., AND ANDERSEN, M. N.: Hemodynamics
of experimental acute aortic insufficiency. Ann
Surg 150: 104, 1959.
AUSTEN, W. G., BENDER, H. WV., WILCOX, B. R.,
AND MoRRow, A. G.: Experimental aortic regurgitation. J Surg Res 3: 466, 1963.
NOLAN, S. P., AND MULLER, W. H.: Comparison
of acute and chronic experimental aortic insufficiency. Surg Forum 13: 210, 1962.
WELDON, C. S., AND COOPER, T.: Aortic flow
characteristics in experimental aortic insufficiency. Surg Forum 9: 325, 1959.
ScHENK, V. G., JR., MENNO, A. D., AND MARTIN, J. W.: Hemodyanmics of chronic experimental aortic insufficiency. Ann Surg 154:
295, 1961.
SCHENK, W. G., JR., AND ANDERSEN, M. N.:
Human ascending aortic blood flow measurements: Immediate application of diagnostic
and physiologic information obtained during
cardiac surgical procedures. Ann Surg 160:
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JONES, J. W., RACKLEY, C. E., BRUCE, R. A.,
DODGE, H. T., COBB, L. A., AND SANDLER,
H.: Left ventricular volumes in valvular heart
disease. Circulation 29: 887, 1964.
WIGGERS, C. J.: Magnitude of regurgitation
with aortic leaks of different sizes. JAMA 97:
1359, 1931.
WICGERS, C. J.: Modern concepts of hemodynamic effects of aortic insufficiency. W Virginia
Med J 56: 327, 1960.
BERGLUND, E., BORST, H. G., DUFF, F., AND
SCHREINER, G. L.: Effect of heart rate on
cardiac work, myocardial oxygen consumption
and coronary blood flow in the dog. Acta
Physiol Scand 42: 185, 1958.
WARNER, H. R., A-ND TORONTO, A. F.: Regulation of cardiac output through stroke volume.
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Ross, J., JR., LINHIART, J. W., AND BRAUNWALD,
E.: Effects of changing heart rate in man by
electrical stimulation of the right atrium: Studies at rest, during exercise, and with isoproterenol. Circulation 33: 549, 1965.
MILLER, D. E., GLEASON, W. L., WHALEN, R. E.,
MORRIS, J. J., AN-D MCINTOSH, H. D.: Effect of
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15.
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DETERMINATIONS OF AORTIC BLOOD FLOW
24. RUSHMER, R. F., SMITH, O., AND FRANKLIN,
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Anginal Pain; Self-Diagnosis:
Sir James Mackenzie
Case 28.-Male. Born 1853.
This patient is a doctor, and has led a healthy, active life in a country practice. He
had a mild attack of typhoid fever in 1880. In 1901, after running a short distance,
his heart became very irregular, and tracings showed the irregularity characteristic
of auricular fibrillation. The attack lasted two hours, and has not recurred up till now
(1923). Since he was 40 years of age he has noticed extra-systoles, at times frequent,
and at other times several months have passed without his noticing them. Beyond
playing golf he has taken no violent exercise. In 1908 he had a severe attack of pain
across the chest and into the left arm. The pain varied in severity, and he could not
be still but had to move about. The attack lasted two hours, when he fell asleep after
10 grains of veronal. The pain began when resting, but seemed to have been provoked
by some digestive disturbance, as he had been partaking freely of large dinners for a
few days before the attack. He was quite well next day, and has had no attacks, though
the pain could be easily provoked at times under special circumstances, as walking
in the cold air, or after meals. This tendency became more evident in 1911, especially
in the evening after a hard day's work. For a time it would disappear, but in later
years it could be more easily provoked. When he makes a sudden effort, as running
upstairs, he becomes breathless, but does not suffer pain. In 1908 he went for a long
walk, and on his return he had to walk rapidly for four miles to catch a train, and
during the last mile he experienced such a feeling of weakness and aching in his feet
and legs that he was unable to continue, and had to stop frequently. After this he
found that walking rapidly for a half mile invariably produced this sensation. Yet he
can play a round of golf in cold and windy weather in comfort-the reason being that
the effort is not continuous....
At the age of 70 he leads still a fairly active life, and having noted the circumstances
that provoke the pain he is able to go about in comfort. Every now and then he forgets,
but the feeling of compression warns him that if he persists the pain will come on, and
on several occasions he has tried how far he can go in spite of the pain, but it becomes
so severe that he is compelled to stop. As soon as he stops walking it begins to pass
off, and in one or two minutes it is entirely gone and he can walk quietly in comfort.
He has noticed that usually a feeling of constriction across the chest precedes the
pain, and the pain is felt vaguely across the chest, but does not go into the arms.
Occasionally he has felt a slight aching in the left jaw and left side of the tongue, with
an increased flow of saliva, which precedes the pain in the chest.-SIR JAMES MACKENZIE: Angina Pectoris. London, Oxford Medical Publications, 1923, p. 176. (Sir
James died Jan. 26, 1925. Obituary. Heart 12:i, 1925.)
Circulation, Volume XXXV, January 1967
Downloaded from http://circ.ahajournals.org/ by guest on April 30, 2017
Direct Determinations of Aortic Blood Flow in Patients with Aortic
Regurgitation: Effects of Alterations in Heart Rate, Increased Ventricular
Preload or Afterload, and Isoproterenol
ROBERT K. BRAWLEY, ANDREW G. MORROW, Harry W. Seipp, Jr. and David
E. Cobb
Circulation. 1967;35:32-45
doi: 10.1161/01.CIR.35.1.32
Circulation is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231
Copyright © 1967 American Heart Association, Inc. All rights reserved.
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