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Transcript
Induced Pressure Gradients Across
Infundibular Zone of Right
Ventricle in Normal Dogs
By John R. Tobin, Jr., M.D., Peter E. Blundell, M.D., Ralph G. Goodrich,
and H. J. C. Swan, M.B., Ph.D., M.R.C.P.
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• During investigations of the effects of sympathomimetic amines on ventricular function
in normal dogs, significant pressure gradients
were observed frequently across the right ventricular outflow tract. The magnitude of these
pressure gradients was greatest in anesthetized
animals infused with isopropylarterenol. Since
no detailed description of such functional right
ventricular outflow-tract pressure gradients
was found in the literature, studies on the
occurrence and mechanism of this phenomenon were initiated.
These experiments demonstrated that infusions of isopropylarterenol induce pressure
gradients, which are largest in late systole, between the sinus of the right ventricle and the
pulmonary artery; that the magnitude of
these pressure gradients always is increased
by the prior administration of either acetyl
strophanthidin or calcium chloride, and that
the genesis of these pressure gradients apparently depends on early vigorous contraction
of the infundibulum of the right ventricle.
Methods
PREPARATION OF DOGS
Mongrel dogs weighing 12 to 18 kg were anesthetized with pentobarbital and restrained in the
supine position. One carotid artery and both jugular veins were exposed. Number 6 Lehman
catheters were introduced and, under fluoroscopic
and manometric control, manipulated into the
pulmonary artery, the sinus of the right ventricle,
and the aortic arch. Number 5 Lehman catheters
From the Mayo Clinic and the Mayo Foundation,
Rochester, Minnesota.
Supported in part by Grant HE-06249 from the
National Institutes of Health, U. S. Public Health
Service.
Received for publication August 7, 1964.
162
were introduced into the superior vena cava for
the injection- of indocyanine green and into a
jugular vein for the infusion of drugs.
INSTRUMENTATION
Statham strain-gauge transducers with equal
sensitivities were used to measure simultaneous
pressures which were recorded on the same base
line. The assembly for calibration of zero reference levels at midthorax and the sensitivities of
multiple manometers in situ have been described.1
The catheter-manometer systems used have frequency responses which are uniform to between
15 and 20 cycles/sec.
When three pressure pulses were recorded simultaneously and at the same sensitivities from
three sites (the sinus and infundibulum of the
right ventricle and the pulmonary artery) in
open-chest dogs, special catheter-manometer systems were used. These consisted of flanged, 19gauge, thin-walled needles, 1 cm long; nylon
tubing with an internal diameter of 0.039 inch
and a length of 12 cm; P23DB Statham straingauge transducers; and 40-350 Heiland galvanometers which were electrically damped by
300 ohms resistance. The frequency response of
such systems is uniform to 35 cycles/sec with variability of ± 10*.
Cardiac output was measured by the indicator dilution technic. Indocyanine green (cardiogreen), 1.0 to 1.5 ml, was injected into the superior vena cava in a concentration of 1.25 mg/
ml. Arterial blood was sampled continuously from
the aortic arch by a vacuum suction system and
drawn through a densitometer, model XC-100,
Waters Corporation, for recording of the dilution curves. After each experiment, the densitometer was calibrated with aliquots of the animal's
blood containing known concentrations of indocyanine dye. Values for cardiac output were calculated by standard methods.2 Stroke volume was
obtained by dividing the cardiac output by the
heart rate.
To determine the exact time of pulmonary
valve closure, a phonocardiogram was recorded
from the right parastemal area at the level of the
third interspace by means of a Sanborn impedance
CircnUiion Resetrcb, Vol. XVI, ttbrutrj 196)
163
INFUNDIBULAR PRESSURE GRADIENTS IN DOGS
Downloaded from http://circres.ahajournals.org/ by guest on April 30, 2017
microphone with a diaphragm, a Sanborn logarithmic amplifier, and a HeMand-C galvanometer with
a frequency response from 0 to 225 cycles/sec
and a variability of ± 4%. Lead n of the electrocardiogram was recorded and used as an additional timing reference to the cardiac cycle.
interval was permitted to elapse and variables
were recorded again (control 3). Isopropylarterenol infusions and subsequent experimental procedures were done also in the manner just described.
EXPERIMENTAL PROCEDURE
Figure 1 iHustrates the method used to measure the systolic ejection period. The mean right
ventricular (sinus) pressure (RVsm) and the
mean pulmonary arterial pressure (PAsm) during systolic ejection were calculated by conventional planimetry. The mean pressure gradient
during systolic ejection (SGm) was obtained by
subtraction of the mean pulmonary arterial pressure from the mean right ventricular (sinus) pressure. The mean pressure gradient was divided by
the mean right ventricular (sinus) pressure to
express the magnitude of the pressure gradient
in relationship to the ventricular pressure.
When relative stability was attained, control
observations (control 1), which included the recording of indicator dilution curves and pressure
pulses, were made during a ten-minute period.
Then, isopropylarterenol (Isuprel hydrochloride,
Winthrop Laboratories) was infused at a constant rate of 2.5 /xg/min by means of a Harvard
syringe. After six minutes of infusion, indocyanine
green-dye curves and pressure pulses were again
recorded. The rate of infusion was increased to
5.0 jitg/min, ar>d after a second six-minute interval of infusion, the same variables were recorded. An exact twelve-minute time interval was
permitted to elapse and another set of records
(control 2) was obtained.
When acetyl strophanthidin or calcium chloride was used, control 2 was followed bv the
injection of 0.5 mg of acetyl strophanthidin or
40 mg/kg of calcium chloride. A twelve-minute
40
-
20
-
CALCULATIONS
Results
ISOPROPYLARTERENOL (TABLE 1)
The effects of isopropylarterenol infusion on
right ventricular outflow-tract pressure gradients in a normal dog are illustrated in figure 2.
PULMONARY ARTERY
RIGHT VENTRICLE Q
Phonocordiogram
EC6
"**
Base Line
FIGURE 1
Systolic ejection period (S.E.P.) is time between onset of ejection (wlien ventricular pressure
first exceeds pulmonary arterial pressure) and end of ejection (when vibration consequent to
pulmonary valve closure appears on phonocardiogram).
CircmUlio* Rtltsrcb, Vol. XVI, February 196)
TOBIN, BLUNDELL, GOODRICH, SWAN
164
TABLE 1
Isopropylarterenol-induced Right Ventricular Outflow-tract Pressure Gradients in Nine Normal Dogs
Experimental period
A. Control
Average
Standard deviation
B. Isopropylarterenol, 2.5 Mg/min
Average
Standard deviation
Downloaded from http://circres.ahajournals.org/ by guest on April 30, 2017
Difference between A and B
Mean of differences^
Standard deviation
C. Isopropylarterenol, 5.0 jig/min
Average
Standard deviation
Difference between A and C
Mean of differences^
Standard deviation
Heart rate
Stroke
volume
beat«/min
ml
Cardiac
output
Syitolic
ejection
period
literg/min
RVsm*
PAim*
mm Hg
mm Hg
Preuure gradient
mm Hg
% of
RVim
160
13.5
2.13
0.143
21
19
18
3.5
0.62
0.016
5
5
2
9
178
15.1
2.75
0.136
27
19
8
30
16
3.9
0.83
0.016
8
6
4
14
18t
1.9}
0.62}
6}
0
6t
4.3
5.1
0.596
0.0184
5.9
3.8
3.9
-0.008
192
16.9
3.26
0.132
26
16
10
36
17
4.6
0.99
0.024
5
3
5
14
321
3.5}
Lilt
-0.012
20.6
3.62
0.863
6}
0.0306
6.1
-3
3.6
8t
3.4
*RVsm is the mean systolic right ventricular (sinus) pressure; PAsm is the mean systolic pulmonary arterial
pressure.
tP<0.01.
tP<0.05.
§ Discrepancies between the mean of individual differences and the apparent arithmetic mean difference are the
result of rounding numbers for average values.
Responses of this magnitude were found in
one third of the studies. The data which describe the effects of isopropylarterenol infusion
in nine normal dogs are listed in table 1.
The infusion of isopropylarterenol at 2.5
/xg/min increased right ventricular pressure
by an average of 6.0 mm Hg and increased
the mean pressure gradient by an average of
6.0 mm Hg. The pulmonary arterial pressure
was unaltered. A significant increase of heart
rate resulted in an average increase of cardiac
output by 0.62 liter/min. The systolic ejection
period was unchanged. When the infusion
rate of isopropylarterenol was increased to 5.0
/xg/min, the average increase of the outflowtract pressure gradient during systolic ejection
was 8.0 mm Hg.
ACETYL STROPHANTHIDIN AND ISOPROPYLARTERENOL
(TABLE 2)
The effects of isopropylarterenol infusion on
right ventricular outflow-tract pressure gradients in a normal dog 12 minutes after the
infusion of 0.5 mg of acetyl strophanthidin are
illustrated in figure 3. The data which describe
the effects of isopropylarterenol infusion in
four normal dogs, after the infusion of 0.5 mg
of acetyl strophanthidin, are listed in table 2.
The infusion of isopropylarterenol at a rate
of 2.5 /xg/min increased right ventricular
pressure by an average of 21 mm Hg and increased the mean pressure gradient by an
average of 19 mm Hg. There was a small and
inconsistent increase of pulmonary arterial
pressure (average 3.0 mm Hg). A consistent
increase of heart rate (average 36 per minute)
was primarily responsible for the average increase in cardiac output of 0.65 liter/min and
for a shortened systolic ejection period. When
the infusion rate of isopropylarterenol was increased to 5.0 /ig/min, the average increase
Circulation Resttrcb, Vol. XVI, Ftbrmtry 196)
165
INFUNDIBULAR PRESSURE GRADIENTS IN DOGS
illustrated in figure 4. The data which describe the effects of isopropylarterenol infusion
in three normal dogs after the infusion of 40
mg/kg of calcium chloride are listed in table 3.
The infusion of isopropylarterenol at a rate
of 2.5 /u,g/min increased right ventricular pressure by an average of 20 mm Hg and increased
the mean pressure gradient by an average of
of the outflow-tract pressure gradient during
systolic ejection was 26 mm Hg.
CALCIUM CHLORIDE AND ISOPROPYLARTERENOL
(TABLE 3)
The effects of isopropylarterenol infusion on
right ventricular outflow-tract pressure gradients in a normal dog 12 minutes after the infusion of 40 mg/kg of calcium chloride are
Control
(mm Hg)
60 i—
Isopropylarterenol (fig /minute)
2.5
5.0
Control
40
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20
PULMONARY ARTERY
RIGHT VENTRICLE
-f-f-
Phonocardiogram
Base Line
RV(m) = 24
SG(m) - 4
27
13
FIGURE 2
Isopropylarterenol-induced right ventricular outflow-tract pressure gradients in normal dog
weighing 12.5 kg. Two control gradients also shown.
Control
(mm Hg)
Isopropylarterenol
2.5
(fig/min)
Control
5.0
60
40
RIGHT VENTRICLE
20
PULMONARY ARTERY
0
C
Phonocardiogram
-J
ECG
Base Line
RV(m) = 26
SG (m) • 12
46
27
45
33
4IB
6
FIGURE 3
Effects of acetyl strophanthidin on isopropylarterenol-induced right ventricular outflow-tract
pressure gradients in normal dog weighing 12.5 kg. Infusion of isopropylarterenol administered 12 minutes after infusion of acetyl strophanthidin, 0.5 mg.
Circulation Rtsurch, Vol. XVI, Ftknury 196}
ownloaded from http://circres.ahajournals.org/ by guest on April 30, 2017
TABLE 2
132 to 156
Range
24 to 38
36
162 to 192
0.74
- 0 . 0 9 to 1.20
— 3.9 to 4.3
30 to 51
2.88 to 3.58
1.0
15.5 to 21.3
40
168 to 186
3.34
0.35 to 1.30
- 1 . 9 to 4.3
18.6
0.65
2.45 to3.70
3.15
1.90 to 3.30
2.50
Cardiac
output
liters/ min
0.4
13.2 to 20.2
17.9
13.9 to 21.1
17.6
ml
Stroke
volume
-0.045 t o - 0 . 0 0 7
— 0.027
0.137 to 158
0.150
-0.049 to—0.003
-0.027
0.144 to 0.155
0.149
0.158 to 0.200
0.176
sec
Systolic
ejection
period
RVsm*
14 to 40
24
38 to 58
46
15 to 27
21
39 to 46
43
18 to 26
22
mm Hg
PAsm*
- 7 to 3
—1
12 to 17
15
— 1 to 5
3
17 to 22
19
14 to 19
16
mm Hg
21 to 37
26
25 to 41
31
12 to 24
19
17 to 28
24
1 to 12
6
60 to 73
68
44 to 62
56
5 to 46
25
% of RVsm
Pressure gradient
mm Hg
*RVsm is the mean systolic right ventricular (sinus) pressure; PAsm is the mean systolic pulmonary arterial pressure.
t Discrepancies between the mean of individual differences and the apparent arithmetic mean differences are the result of rounding numbers for average
values.
Range
Difference between A and C
Mean of differencest
Range
C. Isopropylarterenol, 5.0 jiig/min
181
Average
Range
Difference between A and B
Mean of differencest
Range
13. Isopropylarterenol, 2.5 Mg/min
Average
177
141
Heart rate
A. Control
Average
Experimental period
Effects of Acetyl Strophanthidin on Isopropylarterenol-induced Right Ventricular Outfiow-tract Pressure Gradients in Four Normal Dogs
>
I/I
SO
n
o
o
o
o
z
o
C
o
ov
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n
TABLE 3
132 to 156
142
Heart rate
- 1 8 to 66
28
138 to 204
170
12 to 54
30
156 to 192
3.0 to 11.7
6.0
19.9 to 24.0
22.1
4.8 to 7.1
5.7
19.4 to 23.7
21.7
12.3 to 18.9
16.0
Stroke
volume
ml
0.13 to 3.20
1.51
3.08 to 4.90
3.81
1.03 to 2.03
1.42
3.43 to 3.98
3.71
1.70 to 2.95
2.29
Cardiac
output
liters/min
-0.046 to 0.18
-0.029
0.137 to 0.170
0.153
-0.033 to-0.011
-0.022
0.150 to 0.177
0.159
0.174 to 0.188
5 to 31
19
29 to 43
38
14 to 28
20
38 to 40
39
12 to 24
19
— 6 to 5
1
11 to 17
15
60 to 63
18 to 27
11 to 26
19
62
23
13 to 23
1 to 5
47 to 60
18 to 24
16
53
8 to 29
1 to 7
21
21
4
Pressure gradient
% RVsm
mm Hg
4
16 to 20
18
11 to 17
14
sec
0.182
PAsm*
mm Hg
RVsm*
mm Hg
Systolic
ejection
period
•RVsm is the mean systolic right ventricular (sinus) pressure; PAsm is the mean systolic pulmonary arterial pressure.
t Discrepancies between the mean of individual differences and the apparent arithmetic difference are the result of rounding numbers for average values.
Range
Difference between A and C
Mean of differencest
Range
C. Isopropylarterenol, 5.0
Average
Range
Difference between A and B
Mean of differences
Range
B. Isopropylarterenol, 2.5 Mg/min
Average
172
Range
A. Control
Average
Experimental period
Effects of Calcium. Chloride on Iso)>roi)ijlarterenol-induced Right Ventricular Outflow-tract Pressure Gradients in Three Normal Dogs
O\
8
o
Z
m
u
73
o
71
m
«/>
v>
7)
00
z
o
c
168
TOBIN, BLUNDELL, GOODRICH, SWAN
Control
Isopropylarterenol (jig /min) Control
2.5
5.0
(mm Hg)
60
40
20
PULMONARY ARTERY
RIGHT VENTRICLE 0
•J
Phonocardiogram
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Base Line
«*«
RV(m)=>20
SG(m)=S
38
18
42
25
24
5
FIGURE 4
Effects of calcium chloride on isopropylarterenol-induced right ventricular outflow-tract pressure gradients in normal dog weighing 15 kg. Infusion of isopropylarterenol administered 12
minutes after infusion of calcium chloride, 40 mg/kg.
16 mm Hg. There was a small but consistent
increase of pulmonary arterial pressure (average, 4.0 mm Hg). A larger cardiac output was
the product of consistent increases of heart
rate and stroke volume. When the infusion
rate of isopropylarterenol was increased to
5.0 /ng/min, the average increase of the outflow-tract pressure gradient during systolic
ejection was 19 mm Hg.
The means of the differences between values obtained at the two levels of isopropylarterenol infusion were evaluated for all experiments. In each instance the differences were
small and inconsistent excepting for the small
increases in the outflow-tract pressure gradients.
Comment
" . . . I do not think that either clinicians
or physiologists have yet fully perceived the
bearings which this theory (incorporation of
the bulbus cordis into the right ventricle as
the infundibulum) has on the constitution and
action of the normal heart."—Sir Arthur
Keith.3
At the conclusion of our initial experiments
(table 1), it was apparent that right ventricular outflow-tract pressure gradients could be
induced by isopropylarterenol in normal dogs;
but if the genesis of such pressure gradients
was to be investigated, an invariably successful method of producing them was desirable.
The infusion of epinephrine or norepinephrine at 10 /xg/min induced significant right
ventricular outflow-tract pressure gradients in
10% of studies, but the magnitudes of such
responses were invariably less than those attained with isopropylarterenol. Left ventricular outflow-tract pressure gradients have been
induced in normal dogs by several investigators.4-0 These investigators either infused sympathomimetic amines4 or combined such infusions with a procedure which reduced the
stroke volume/''" Our right ventricular outflow-tract pressure gradients were not effectively magnified by either prior phlebotomy
or infusion of massive concentrations of isopropylarterenol.
Isopropylarterenol enhances the rate and
force of myocardial contraction.7 If the inotropic effect were primarily responsible for
the development of the right ventricular outflow-tract pressure gradients in normal dogs,
other agents which enhance the force of
myocardial contraction might be additive and
magnify those pressure gradients. The experiCircuUlion Reiurcb. Vol. XVI, F«4r«rj 1963
INFUNDIBULAR PRESSURE GRADIENTS IN DOGS
169
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ments detailed in tables 2 and 3 showed that
the right ventricular outflow-tract pressure
gradients induced by isopropylarterenol in
normal dogs are indeed enhanced by the prior
administration of either acetyl strophanthidin
or calcium chloride.
Figure 5 summarizes graphically the average results of these experiments. The pressure
gradients varied for different experimental periods, with respect to both the absolute values
and their percentage relationship to the ventricular pressures. When the pressure
gradient increased, right ventricular pressure
increased simultaneously, but the pulmonary
arterial pressure did not rise.
The infusion of isopropylarterenol at 5.0
/jLg/min produced responses which did not
differ substantially from those obtained with
2.5 /xg/min. The infusion of acetyl strophanthidin or calcium chloride alone did not induce
right ventricular outflow-tract pressure gradients which differed significantly from those
observed during control periods. Yet, the ad-
ministration of either acetyl strophanthidin or
calcium chloride, prior to the infusion of isopropylarterenol at 2.5 fig/min, resulted in responses which greatly exceeded those accompanying the infusion of isopropylarterenol
alone. These observations indicate that isopropylarterenol was primarily • responsible for
the genesis of these gradients and its effect
was probably maximal, but pretreatment with
acetyl strophanthidin and calcium chloride
resulted in a substantially greater infundibular contraction. Thus, a mechanism other than
simple inotropic stimulation may be induced
by the addition of these substances. The data
indicate that the relatively small increases in
cardiac output were not major factors in the
genesis of these pressure gradients,
Braunwald and co-workers,8'9 in reporting
studies of hypertrophic subaortic stenosis in
man, emphasized the variable nature of the
pressure gradients between the left ventricle
and the brachial artery and suggested that
this variability depends on changes in the
Controls
(9, Mean and ± I S.D.)
Calcium Chloride
Acetylstrophanthidin
(3, Mean and Range)
(4, Mean and Range)
IsopropylorterenoH/ig)
Isopropylarterenol l/iq.)
Control
2.5
5.0
Control
60
MEAN PRESSURES
30
(mm Kg)
0
SO
PRESSURE/
GRADIENT/
RV
*
(%)
1%J
40 -
y
CARDIAC
^
OUTPUT
(L./minute)
Y
y
Y
V
FIGURE S
Hemodynamic features of isopropylarterenol-induced right ventricular outflow-tract pressure
gradients in normal dogs (average values).
Circulation Resurcb. Vol. XVI. Ptbrusry 1961
170
TOBIN, BLUNDELL, GOODRICH, SWAN
A ' JU JU -UL
ANGIO MARKER >MMAl|MMAl M l A
ANGIOCARDIOGRAM
(On« Cardiac Cycle)
(mm Hg)
80 —
AORTA
40
PULMONARY
ARTERY
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RIGHT
VENTRICLE
-
m
m
FIGURE 6
Simultaneously recorded pressure pulses from sinus and infundibulum of right ventricle and
from pulmonary artery during filming of cineangiogram of outflow tract of right ventricle of
a 14-kg dog. Cineangiogram marker (above) identifies timing of individual frames (1-1V)
reproduced to right. Note the contraction of infundibulum (frame 111) associated with rising
sinus pressure and falling infundibular pressure. Diagonal line traversing record indicates
syringe travel during injection of Renovist (mixture of sodium and methylglucamine diatrizoates) 30 ml.
force of ventricular contraction. Such pressure
gradients have been magnified with both isopropylarterenol10 and ouabain.11 Selective left
ventricular angiograms have demonstrated
systolic narrowing of the left ventricular outflow tract and have suggested that the obstruction is maximal in late systole.
Figure 6 illustrates the simultaneous recording of a cineangiogram and three pressure
pulses. The pressure pulses were recorded directly from the sinus and infundibulum of
the right ventricle and from the pulmonary
artery of an open-chest dog. The animal had
received 0.5 mg of acetyl strophanthidin and
was being infused with 5.0 /u.g/min of isopropylarterenol. This experiment demonstrated that a right ventricular outflow-tract
pressure gradient exists between the sinus of
the right ventricle and the infundibulum of
the right ventricle during systole and that the
cross-sectional area of the lowest portion of
the outflow tract is smallest in late systole.
The classic studies of Keith'' demonstrated
that the bulbus cordis appears in a developmental stage of the heart in all vertebrate embryos and that it does not disappear from the
mammalian heart but becomes incorporated
into the right ventricle, forming the outflow
tract or infundibulum. There is ample evidence that in normal sequence the sinus of the
right ventricle is activated and contracts before the infundibulum.12 If the sequence of
right ventricular activation or contraction were
altered, premature contraction of the infundibulum might be responsible for the right
ventricular outflow-tract pressure gradients induced in these normal dogs.
The sequence of ventricular activation was
Circulation Research, Vol. XVI, February 1965
INFUNDIBULAR PRESSURE GRADIENTS IN DOGS
171
CONTROL
19.7 msec
ISOPROPYLARTERENOL
19.6 msec
Control
/6.5
Acetylstrophanthidin
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22.0
Calcium Chloride
FIGURE 7
Effects, in a 20-kg dog, of isopropylarterenol-induced pressure gradients on temporal relationships of peak electromyographic potentials recorded directly from body (A) and infundibulum
of right ventricle (B).
investigated by implanting bipolar electrodes
in the right ventricular wall of two open-chest
dogs (fig. 7). One electrode (A) was placed
in the anterior wall in the region of the anterior papillary muscle, and the second (B)
was placed in the outflow tract immediately
beneath the pulmonary valve. Under controlled conditions, the maximum peak potential recorded from electrode A preceded the
maximum peak potential from electrode B by
19 msec. When large gradients were produced
in the manner previously described, the sequence of ventricular activation was not altered.
The nature of right ventricular contraction
was also investigated by analysis of the pressure pulses recorded directly from the sinus
and infundibulum of the right ventricle and
from the pulmonary artery in open-chest dogs
(fig. 8). When pressure gradients were induced, the initiation sequence of contraction
was not altered, but the contours of the pressure pulses and the time intervals between
them were altered. The interval between the
onset of contraction in the sinus and in the
infundibulum decreased to 10 msec, and the
CircuUtion Reietrcb, Vol. XVI, ftbrtury 196)
interval between the peak pressures (infundibular peak preceding sinus peak) increased
to 46 msec. The infundibular systolic pressure
became similar to the systolic pulmonary arterial pressure, rising sharply to an attenuated
peak and falling abruptly to the level of pulmonary arterial diastolic pressure as the pressure in the sinus of the ventricle continued to
rise to a delayed peak. These pressure pulse
contours are similar to those described by
Rodbard and Shaffer13 and Johnson14 in patients with muscular (functional) infundibular stenosis.
Altered tonus of the infundibular portion of
the right ventricle has been suggested as a
mechanism involved in the "cyanotic spells"
associated with tetralogy of Fallot,lr> in the
reduction of left-to-right shunts associated
with ventricular septal defects,10 and in the
persistence of right ventricular outflow-tract
pressure differences after pulmonary valvulotomy.17 It has been assumed that these findings were characteristic of the hypertrophied
infundibulum of the diseased heart. However,
our experiments demonstrate that severe right
ventricular outflow-tract pressure gradients
TOBIN, BLUNDELL, GOODRICH, SWAN
172
ACETYLS TROPHA N THIDIN
Control
Isopropylorterenol
Control
Isopropylorterenol
27
25
43
25
27
24
53
22
25
22
24
22
(mm Hg)
60 r-
40
-
PULMONARY
ARTERY 2
0
RIGHT
VENTRICLE
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Base Line
R.V.(m)
Sinus
Infundibulum
P.A.(m)
FIGURE 8
Simultaneously recorded pressure pulses from sinus and infundibulum of right ventricle and
from pulmonary artery of a 15-kg open-chest dog. Effects of isopropylarterenol alone and
after administration of acetyl strophanthidin.
can be induced in normal dogs by drugs which
alone or in combination alter the rate and
force of cardiac contraction.
of intravascular and intracardiac pressures. In
Medical Physics, vol. 3, ed. by O. Classer.
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Summary
2. HAMILTON, W. F., MOORE, J. W., KINSMAN, J.
M., AND SPURLINC, R. G.: Studies on the cir-
In these experiments we have demonstrated
that:
1. Right ventricular outflow-tract pressure
gradients of significance can be induced in
normal dogs by a sympathomimetic amine
which increases the rate and force of ventricular contraction.
2. Such outflow-tract pressure gradients are
magnified by the addition of other inotropic
drugs, such as acetyl strophanthidin and calcium chloride.
3. These outflow-tract pressure gradients are
not the result of an increase in the volume
and rate of blood flow but are due to
forceful contraction of the infundibulum.
culation. IV. Further analysis of the injection
method, and of changes in hemodynamics under physiological and pathological conditions.
Am. J. Physiol. 99: 534, 1932.
3. KEITH, A.: Fate of the bulbus cordis in the
human heart. Lancet 2: 1267, 1924.
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Induced Pressure Gradients Across Infundibular Zone of Right Ventricle in Normal Dogs
JOHN R. TOBIN, Jr., PETER E. BLUNDELL, RALPH G. GOODRICH and H. J. C. SWAN
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Circ Res. 1965;16:162-173
doi: 10.1161/01.RES.16.2.162
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