Download PDF - Circulation Research

Hemodynamic Consequences of Induced
Changes in Blood Volume
By James Conway, M.D., Ph.D.
With the technical assistance of Miklos
Gellai
Downloaded from http://circres.ahajournals.org/ by guest on June 18, 2017
• The acute effects of changes in blood
volume on cardiac performance have been
investigated intensively in the past in order
to determine the relationship between filling
pressure and cardiac output.1 The influence
of sustained changes in blood volume on the
entire circulation is, however, less well known.
Yet an exploration of a possible interaction between the blood volume on the one hand and
cardiac output and peripheral resistance on
the other, is important since it might reveal
that the control of the circulation and possibly
blood pressure itself could be affected by
changes in blood volume.
In the present investigation, therefore,
blood volume has been increased by transfusion or reduced by hemorrhage, while the subsequent hemodynamic changes have been
measured over periods from two to ten hours.
Since it is known2"4 that cardiac output and
peripheral resistance vary with hematocrit,
infusions of dextran or packed red cells have
been used after transfusion or bleeding in
order to minimize the anticipated changes in
that variable.
Methods
Trained, unaesthetized dogs weighing approximately 20 kg have been used throughout this
study. They were prepared for the experimental
procedures at least one week in advance by implantation of polyvinyl catheters, (2 mm, I.D.).
These were introduced under pentobarbital sodium (Nembutal) anesthesia (30 mg/kg) through
an incision in the side of the neck. One catheter
From the Departments of Medicine and Physiology,
University of Michigan, Ann Arbor, Michigan.
Supported by Grant HE-07764 from the U. S.
Public Health Service, a grant-in-aid from the Michigan Heart Association, and the Phoenix project of
the University of Michigan.
Accepted for publication August 9, 1965.
190
was then passed into the right atrium or ventricle
via the external jugular vein, and another into the
aorta via the carotid artery. By means of a sharp
probe the free ends of the catheters were run
under the skin to the back of the neck and exteriorized through individual puncture holes. The
catheters were filled with saline and plugged
with steel pins.
The animals were repeatedly brought down to
the testing laboratory and trained to lie unrestrained in the prone position on a padded surface for a period of approximately one hour. During these training exercises blood pressure, and
occasionally also the cardiac output and plasma
volume were measured. On the day of the experimental procedures the dogs were fasted but were
otherwise given no premedication. For blood
pressure measurements connections were made
via polyvinyl tubing (2 mm I.D.) 10 cm in
length for each catheter to a Statham strain
gauge (P23B or P23G). The zero level was
taken to be 8 cm above the table top. The arterial catheter was then connected to a Gilford
densitometer for cardiac output measurements by
the indicator dilution method. The dye, indigocarmine (8 mg in 1 ml water), was injected into
the prefilled cardiac catheter. For inscription of
the dilution curves arterial blood was drawn at
30 ml/min.
Cardiac output measurements were always
made in duplicate and after the inscription of
each curve a wedge of standard optical density
was inserted into the light beam of the densitometer to check the gain of the apparatus. The
output curves were calibrated at the end of the
experimental procedures by the addition of known
quantities of dye to 10 ml samples of blood. These
were drawn through the densitometer at the
same rate as used above. Records were made by
means of a Gilson polygraph and for the cardiac
output curves a servo-channel of the machine
gave dye curves approximately 80 mm in height.
The Stewart-Hamilton formulae were used for the
calculation of cardiac output.5 From this and the
mean circulation time, corrected for catheter
delay, the central blood volume was calculated.
Total peripheral resistance was expressed in
units, as the ratio of mean arterial blood pressure
in mm Hg divided by cardiac output in liters/
min.
Circulation Research, Vol. XV1U, February 1966
CARDIOVASCULAR FUNCTION AND BLOOD VOLUME
Downloaded from http://circres.ahajournals.org/ by guest on June 18, 2017
After drawing a control blood sample the plasma
volume was measured0 with radioactive iodinated
human serum albumen.* A dose of approximately
5 fxc was used for each measurement of plasma
volume and samples of blood were drawn 10, 15,
and 20 minutes after injection for extrapolation
to the time of injection to determine the
initial mixing volume. The hematocrit of arterial
blood was measured in duplicate at the same
time. An effort was made to reduce the volume
of blood withdrawn for both the blood volume
and cardiac output determinations, and also to
limit the saline used to clear the catheters after
drawing blood. For the cardiac output measurements the loss of blood was minimal since the
sample was reinfused immediately after the determination was completed, and only 5 ml of
saline were injected to clear the catheters of
blood. For an hematocrit determination 2 ml of
blood were withdrawn; for a plasma volume and
hematocrit determination, a total of 20 ml of
blood was withdrawn and 25 ml of saline given in
flushing the catheters.
During each experiment the dogs were given
200 units of heparin/kg at hourly intervals; no
anticoagulant was used on days between experimental procedures.
With the exception of procedure no. 1, which
required multiple transfusions, the animals were
always infused with their own (autologous)
blood, which had been collected by aseptic techniques five or six days before each experiment
and preserved in commercial ACD solution. The
volume of fluid selected for infusion or bleeding
was limited to approximately 10% of the estimated
normal blood volume in order to avoid acute embarrassment to the circulation and to stay within
the range of possible physiological change. The
volume of the ACD solution infused has not been
included in the volume of blood transfused.
Bleeding or infusion of liquid was always done
slowly, over a period of approximately 20 minutes, to minimize the activation of neurogenic
reflexes. No adverse systemic reactions or evidence of discomfort were observed after any of
the infusions or during the measurements of cardiac output or blood pressure.
After control measurements of blood volume
and hematocrit, the cardiac output and intravascular pressures were determined. Blood was then
infused or withdrawn and the physiological measurements repeated at specific intervals for several
hours, timed from the beginning of the transfusion or bleeding. In the intervals between
measurements the dog was returned to his run
and allowed free movement. In order to limit the
change in hematocrit, blood transfusions were
*Iso-Serve Inc., Cambridge, Massachusetts.
Circulation Research, Vol. XVIII, February 1966
191
accompanied by infusions of dextran, 6% solution
in saline (mean mol wt 75,000),* and in the
bleeding experiments by infusion of autologous
packed red cells. Optimal amounts of these for
each type of procedure were determined in preliminary experiments. In each experiment the
hematocrit was kept within 5% of the control
value.
Six procedures were used:
1. Sustained Expansion in Blood Volume. In ten
experiments on eight dogs, after the control
measurements, three infusions of 90 ml of blood
and 70 ml of dextran were made at intervals of
two and one-half hours. Seven experiments were
performed with homologous blood but in the
others autologous blood was used. Cardiac output
and blood pressure were measured at intervals of
two and one-half hours for a period of ten hours.
Blood volume and hematocrit were determined
before each cardiac output measurement. The
entire group of control measurements were repeated on the following morning, 24 hours after
the first infusion.
2. Short-Term Expansion. In seven experiments
on five dogs, the effect of the infusion of 100
ml of blood plus 50 ml of dextran on cardiac
output and blood pressure was measured at
half-hourly intervals over a period of two and
one-half hours. Blood volume and hematocrit
were measured at the beginning and at the end
of the procedure.
3. Short-Term Expansion During Ganglionic
Blockade. In seven experiments on five dogs,
the preceding experiment was performed after the
administration of pentolinium, 7.5 mg iv + 7.5
mg sc. This amount blocked the pupillary light
reflex. Subcutaneous doses of the drug were then
repeated to maintain this condition throughout
the period of observation. In these experiments
the first measurement of cardiac output after the
infusion of blood and dextran was omitted because by this time the dogs tended to become
restless since they had been on the experimental
table for a period exceeding one hour while
ganglionic blockade was being established and
the transfusion performed. In all other respects
the experiment was the same as the preceding
one.
4. Hemorrhage With the Replacement of Red
Cells. In eleven experiments on six dogs, after
control measurements, 150 ml of blood was withdrawn. Cardiac output, blood pressure, and hematocrit were measured at half-hourly intervals for
four hours. Since preliminary experiments had
shown that the hematocrit reached its minimum
value at the third hour, 50 ml of packed red cells
•Supplies of dextran were generously provided by
the Pharmachem Corporation, New York.
CONWAY
192
Downloaded from http://circres.ahajournals.org/ by guest on June 18, 2017
were reinfused after completion of the measurements of blood pressure and cardiac output at
the two and one-half hour period. In seven experiments the period of observation was extended
from four and one-half to five and one-half hours.
5. Sustained Reduction in Blood Volume. In
seven experiments on six dogs, 150 ml of blood
were withdrawn as in the previous experiment
and packed red cells were replaced after two
hours. Another 150 ml of blood were then withdrawn and 50 ml of packed cells replaced after
an additional hour. Cardiac output and pressure
measurements were made at two, four, six, and
seven hours after the first withdrawal of blood.
Blood volume and hematocrit were measured at
the beginning and the end of the experiment.
6. Controls. Three types of control procedures
were studied. In seven experiments cardiac output
and arterial and venous pressures were measured
Meoi
Aortic
Blood
Pressure
at hourly intervals over a period of five hours to
determine whether trends would be evident during the day in the absence of transfusions. To
detect possible hemodynamic effects of administered blood, five experiments were done in the
same manner with administration of two transfusions of 100 ml of blood; one after the control
measurements and one two and one-half hours
later. Immediately after each transfusion was completed, however, the same volume of blood was
withdrawn.
Finally, in five experiments a single infusion of
50 ml of dextran was given and cardiac output
and blood pressure were followed for two and
one-half hours as in procedures two and three.
Blood volume and hematocrit were also determined at the beginning and end of all these procedures.
+30
+20
+ , 0
i
0
0
50
7.5
10.0
(tig.I)
T I M E (hrs)
FIGURE 1
Hemodynamic effects over a ten-hour period of three transfusions of blood and dextran (mean
± SEM, 10 experiments). Mean initial value is given with mean changes (± 1 SEM). By means
of the significance ratio the significance of differences from the initial value are given. * indicates
P<0.01 and • • indicate P K 0.001. For the blood volume curves, the measured values are
indicated by dots but the line includes calculated changes immediately resulting from transfusions or hemorrhage.
Circulation Research, Vol. XV111, February 1966
193
CARDIOVASCULAR FUNCTION AND BLOOD VOLUME
Downloaded from http://circres.ahajournals.org/ by guest on June 18, 2017
Results
1. Sustained Expansion in Plasma Volume.
In this group of experiments, blood and
dextran were administered on three successive occasions, two and one-half hours apart.
After each infusion the blood volume tended
to return toward normal but the reduction
did not equal the quantity of fluid infused
(fig. 1) and the measured total blood volume before each transfusion increased. Dilution of the infused blood with dextran prevented a rise in the hematocrit, but with
successive infusions there was a slight overcorrection of the tendency to hemo-concentration and the mean hematocrit declined
from 38 to 35% at seven and one-half hours.
The changes in central blood volume followed the increases in total blood volume and
of end diastolic pressure. This association,
which has been emphasized by Gauer and
Henry,1 was characteristic of most of these
experiments. The mean blood pressure rose
with the first infusion from 92.2 to 112 mm
Hg and remained at this level throughout the
ten-hour period of observation. In spite of a
mean elevation in end diastolic pressure of
approximately 6 cm water, the heart rate and
the cardiac output changed little throughout
the experiment. The mean total peripheral
resistance rose from a control value of 33.2
to 40.0 units at two and one-half hours and remained elevated. The significance ratio showed
that the changes in blood pressure and peripheral resistance were significant (P<0.001).
On the following day, 24 hours after the first
infusion, all measurements had returned to
control levels.
Since the peripheral resistance and cardiac
output levels appeared to be stable by the
time the first observations were completed,
the sequence of events during the first two
and one-half hours after the transfusion was
examined more closely in the next two procedures.
2. Short-Term Expansion. The blood volume
was expanded by an infusion of 100 ml of
blood plus 50 ml of dextran and measurements
were made more frequently, at one-half hour
intervals, for two and one-half hours (fig. 2A).
Circulation Reiearch, Vol. XVIII, February 1966
Mean
Aortic + 30
Blood
20
Pressure
+ 10
mm Hg
95.9
Ld
0
<
0
3
a.
0
Central
Blood
Volume
ml
+40]
Hemotocrit
371
(fig.2'A)
458]
-1
-40^
0
0.5
1.0
1.5
2.0
2.5
TIME(hrs)
FIGURE ZA
Hemodynamic effects over a two and one-half hour
period of a single infusion of blood and dextran
(mean ± SEM, seven experiments). For symbols see
legend to figure 1.
End diastolic pressure was elevated at one-half
hour and along with this cardiac output, heart
rate, and blood pressure rose. The change in
output was, however, small, 0.4 liter/min, and
two hours after the infusion it had returned
to the control level. The calculated peripheral resisatnce then rose significantly above
the control value of 38.7 to 46.9 units ( P <
0.001).
In order to determine whether the sequence
of changes in the cardiovascular response to
transfusion resulted primarily from reflex
adjustments, this experiment was repeated
after pharmacologic blockade of the dogs'
autonomic nervous system.
CONWAY
194
Mean
Aortic
Blood
Pressure
mm Hg
+ 3
°;
20
Cardiac
W
0
<
0
Downloaded from http://circres.ahajournals.org/ by guest on June 18, 2017
3
i
d
a.
0
o
Hematocrit
(tig.2 B)
0.5
1.0
1.5
2.0
TIMEKhrs)
FIGURE 2B
Hemodynamic effects over a two and one-half hour
period of a single infusion of blood and dextran during autonomic blockade with pentolinium (mean ±
SEM, seven experiments). For symbols see legend to
figure 1.
3. Short-Term Expansion During Autonomic
Blockade. The pattern of response seen in the
previous group of experiments was again observed in dogs with ganglionic blockade (fig.
2B). The initial heart rate, 135 beats/min, was
high because of the autonomic blockade, and
changed little throughout the procedure. The
mean initial cardiac output of 3.2 liters/min
after increasing at the first hour returned to
the control level at the next half-hour. The
mean level of blood pressure increased from
an initial value of 99.6 to 132.6 mm Hg in
two and one-half hours with a similar rise
in mean total peripheral resistance, from 32.8
to 41.5 units (P<0.01).
Since these changes in resistance after
transfusion were not expected, and the mechanism for them not evident, it was decided
next to investigate whether reduction in
blood volume would produce the contrary
result.
4. Hemorrhage With Replacement of Red
Cells. Withdrawal of 150 ml of blood from the
circulation reduced end diastolic pressure and
central blood volume. There was an immediate increase in heart rate, a small decrease
in cardiac output, and a proportionate increase in peripheral resistance (fig. 3). The
heart rate returned to the control level at two
and one-half hours and cardiac output at
three and one-half hours. The combination
of a minor fall in blood pressure and a rise
in cardiac output evident at four and one-half
hours resulted in a reduction in mean total
peripheral resistance from the control value
of 30.1 to 26.9 units which, though unimpressive, was significant (P<0.01). The reduction in resistance persisted to five and one-half
hours in the seven experiments which were
extended to this period.
5. Sustained Reduction in Blood Volume.
Results obtained in this experiment were
similar to those of the preceding one (fig. 4),
but with the more prolonged reduction in
blood volume, there was a gradual decline
of mean blood pressure throughout the experiment from 105 to 93 mm Hg. Cardiac
output rose from an initial value of 2.9 to
3.2 liters/min at the seventh hour, and the
overall reduction in peripheral resistance over
the seven-hour period was greater than in
the preceding experiment, falling from 39.9
initially to 30.9 units. All these changes were
significant (P<0.01). It may be noted incidentally that the heart rate in this group
increased after the first hemorrhage and
remained elevated to the end of the experiment.
6. Controls. Repeated measurements of blood
pressure, cardiac output, and hematocrit at
hourly intervals over a period of five hours
showed small variation during the period of
observation. The mean control values were 108
(SE 4.3) mm Hg for blood pressure, 3.7 (SE
Circulation Research, Vol. XVIII, February 1966
195
CARDIOVASCULAR FUNCTION AND BLOOD VOLUME
Mean
Aortic
Blood
Pressure
+10
105
-10
Cordioc+300,
Output
ml/min W50J
Cardiac
Rote
b/min
o
<
0
LJ
Downloaded from http://circres.ahajournals.org/ by guest on June 18, 2017
d
ir
Hemotocrlt 4 0 . 6 1
"' J
4.5
(fig.3)
TIME (hrs)
5.5
»SEVEN EXPTS«
FIGURE 3
Hemodynamic effects over a five and one-half hour period of a single hemorrhage with replacement of red cells (mean ± SEM, 11 experiments). For symbols see legend to figure 1.
0.74) liters/min for cardiac output and at
five hours these values were 114 (SE 3.1) mm
Hg and 4.0 (SE 0.73) liters/min, respectively.
With the administration and withdrawal of
blood there was likewise very little change
in blood pressure or cardiac output, the
mean initial values being 106 (SE 2.9) mm
Hg and 3.7 (SE 0.21) liters/min. After five
hours during which 100 ml of blood had
been administered and then withdrawn on
two occasions, the mean arterial pressure was
107 (SE 3.9) mm Hg and cardiac output 4.1
(SE 0.65) liters/min. In none of these experiments therefore, were there significant changes
in peripheral resistance, nor were directional
trends in cardiovascular performances apparent in the course of the day.
The infusion of 50 ml dextran caused no
systemic reactions and produced little change
Circulation Research, Vol. XV111, February 1966
in cardiac output in any animals at any of
the half-hourly measurements. The mean
control value was 3.7 (SE 0.38) liters/min
and after two and one-half hours 3.3 (SE 0.31)
liters/min. The blood pressure varied little
in this period and the mean peripheral resistance which was 29.3 (SE 2.9) units initially
was 33.1 (SE 4.0) at two and one-half hours.
Discussion
Blood volume expansion over a period of
ten hours left the cardiac output practically
unchanged despite an increase in filling
pressure and central blood volume. Peripheral resistance however, increased by approximately 25% over the control value. The
absence of a demonstrable cardiac response
can not be ascribed to the development of
congestive heart failure since no tachycardia
196
CONWAY
Downloaded from http://circres.ahajournals.org/ by guest on June 18, 2017
occurred and the rise in end diastolic pressure
was small (6 cm water). The restoration of
blood volume, hematocrit, and cardiovascular
parameters to normal levels by the next
morning is probably the result of the removal
of protein and cells from the circulation, which
is known to occur in the dog.7' 8
Although it has been shown that cardiac
output does not necessarily increase in proportion to the rise in filling pressure, the
absence of change in output was unexpected.
A closer study of the initial phase of the
response revealed a small increase in cardiac
output and heart rate immediately after the
transfusion; this disappeared after one and
one-half hours while blood pressure remained
elevated and peripheral resistance rose to
Central
Blood
Vblum,
Htmotocrit
approximately 20% above the control value in
two hours.
The immediate response to the transfusion
was therefore a small and transient increase in
cardiac output and after hemorrhage cardiac
output decreased. The change in output was, as
reported by others,9*11 not proportional to
the change in end diastolic pressure. Fowler,
et al.12 have also noted that the initial increase in output to transfusion was transient
and in their experiments was no longer evident after 20 minutes. Similarly, in studies on
man, those who have observed a correlation
between filling pressure and cardiac output
have made their observations during the
actual expansion or contraction of blood volume,13 whereas those who were unable to
+40]
482^
_ ^
:s
4Q3
3
4
TIME (hrs)
FIGURE 4
Hemodynamic effects over a seven-hour period of two hemorrhages with replacement of red
cells to minimize changes in hematocrit (mean ± SEM, 7 experiments). For symbols see
legend for figure 1.
Circulation Research, Vol. XVIII, February 1966
197
CARDIOVASCULAR FUNCTION AND BLOOD VOLUME
Downloaded from http://circres.ahajournals.org/ by guest on June 18, 2017
demonstrate this relationship made their observations after changes in blood volume had
been produced.14"16 Experiments in the anesthetized dog in which serum transfusions
were followed for four hours, have shown a
pattern of response similar to that observed
in the present experiments, with an initial
increase in cardiac output which returned to
control level in one hour. In only two of five
dogs, however, was an increase in resistance found at this time. Other observations
consistent with the present series of experiments have been the incidental reports of an
increase in resistance two hours after large
blood transfusions17 and reduced resistance
some hours after hemorrhage.18
It has been suggested that the inability to
demonstrate a consistent relationship between
filling pressure and cardiac output in the intact animal is due to the interference of regulative reflexes.19' 20 The immediate response
to both transfusions and hemorrhage in the
present study was modified almost certainly
by neurogenic reflexes since they evoked
prompt changes in heart rate. Although it has
been shown that reflexes initiated by distension
of the central venous system elevate arterial
pressure,21'22 the delayed rise in resistance
and the observation that the pattern of response to the expansion in blood volume was
unaffected by autonomic blockade, make it
unlikely that the changes of resistance seen
in the present study are the result of neurogenic regulation.
Changes in resistance which occur after
bleeding are consistent with those occurring
after transfusion and suggest that both are
the result of changes in blood volume. The
mechanism which restores cardiac output and
increases resistance is unknown. Its occurrence
under autonomic blockade suggests that it
may be similar to the mechanism operating in
anemia and polycythemia.2-4 It seems possible the changes in peripheral resistance
with transfusion and hemorrhage may be the
same as those concerned with autoregulation23
and with oxygen delivery to the tissues.24'23
The primary effect of changing blood volume is almost certainly on cardiac output but
Circulation Research, Vol. XVIII, February 1966
secondary adjustments then emerge which
affect peripheral resistance and restore cardiac output to normal. This raises the possibility that some part of the long-term control of the circulation might be an indirect
one through the control of blood volume. If
it can be demonstrated that this persists over
periods of days, it would lend support to the
idea that chronic hypertension can result
from derangements of fluid volume control.
Such a concept has, in fact, been postulated
to occur after the application of a Goldblatt
clamp to the renal artery. 2627
Summary
The effects of transfusion or bleeding on
cardiac output and blood pressure have been
followed for periods of seven to ten hours in
trained, conscious dogs.
When blood volume is increased by transfusion of blood, supplemented by dextran to
minimize the expected change in hematocrit,
cardiac output and blood pressure increase
initially. After one and one-half hours the
cardiac output returns to the initial level but
blood pressure remains elevated and calculated peripheral resistance increases. This
state has been maintained for a period of ten
hours by repeated transfusion.
After bleeding, with replacement of packed
cells, again to minimize the change in hematocrit, cardiac output decreases initially and
peripheral resistance increases, but after three
hours, output returns to its former level,
and peripheral resistance falls below the control value. These changes become more prominent when a second hemorrhage is performed
two hours after the first one. The reduction
of resistance was then maintained for seven
hours.
These findings demonstrate that the effects
of changes in blood volume are not limited
to the acute changes in cardiac output and
filling pressure. After periods of one to three
hours, changes in peripheral resistance also
become evident.
References
1. GAUER, O. H., AND HENRY, J. P.: Circulatory
basis of fluid volume control. Phys. Rev. 43:
423, 1963.
CONWAY
198
2.
AND WERKO, L.: The effect of experimentally
induced hypervolemia on cardiac function in
normal subjects and patients with mitral stenosis. J. Clin. Invest. 38: 117, 1959.
LILJESTRAND, G., AND STENSTROM, N.: Work of
the heart during rest. II. The influence of
variations in the hemoglobin content on the
blood flow. Acta Med. Scand. 63: 130, 1926.
3.
4.
GUYTON, A. C., AND RICHARDSON, T. W.: Effect
15. WARREN, J. V., BRANNON, E. S., STEAD, E. A.,
of hematocrit on venous return. Circulation
Res. 9: 157, 1961.
AD MERRILL, A. J.: The effect of venesection
and the pooling of blood in the extremities on
the atrial pressure and cardiac output in
normal subjects with observations on acute
circulatory collapse on three instances. J. Clin.
Invest. 24: 337, 1945.
FOWLER, N. O., BLOOM, W. L., AND WARD, J.
A.: Hemodynamic effects of hypervolemia
with and without anemia. Circulation Res.
6: 163, 1958.
5.
HAMILTON,
W. F., MOORE,
J. W.,
KINSMAN,
16. WARREN, J. V., BRANNON, E. S., WEENS, H. S.,
AND STEAD, E. A.: Effect of increasing the
blood volume and right atrial pressure on the
circulation of normal subjects by intravenous
infusions. Am. J. Med. 4: 193, 1948.
J. M., AND SPURLINC, R. G.: Studies on the
circulation. IV. Further analysis of the injection method, and of changes in hemodynamics under physiological and pathological conditions. Am. J. Physiol. 99: 534, 1932.
17.
Downloaded from http://circres.ahajournals.org/ by guest on June 18, 2017
Simultaneous measurement in dogs of plasma volume with lIsl human albumin and
T-1824 with comparisons of their long-term
disappearance from plasma. Am. J. Physiol.
175: 240, 1953.
7.
HUCGINS, R. A., SMITH, E. L., AND SEIBERT, R.
18.
19. FRYE, R. L., AND BRAUNWALD, E.: Studies on
Starling's law of the heart. I. The circulatory
response to acute hypervolemia and its modification by ganglionic blockade. J. Clin. Invest. 39: 1043, 1960.
8. HAVTER, C. J., CLAPHAM, W. F., MILLS, I. H.,
9. FERGUSON, T. B., GRECC, D. E., AND SHADLE,
O. W.: Effect of blood and saline infusion
on cardiac performance in normal dogs with
arteriovenous fistulas. Circulation Res. 2: 565,
1954.
10.
FERGUSON, T. B., SHADLE, O. W., AND GREGG,
D. E.: Effect of blood and saline infusion on
ventricular end diastolic pressure, stroke
work, stroke volume and cardiac output in
the open and closed chest dog. Circulation
Res. 1: 62, 1953.
11.
12.
14.
20.
WERKO, L., SANNERSTEDT, R., VARNAUSKAS, E.,
AND Bojs, G.: Experimentally induced hypervolemia during ganglionic blockade. Scand. J.
Clin. Lab. Invest. 14: 289, 1962.
21. LEDSOME, J. R., AND LINDEN, R. J.: A reflex in-
crease in heart rate from distension of the
pulmonary-vein-atrial junctions. J. Physiol.
170: 456, 1964.
22. PINKERSON, A. L., AND KOT, P. A.: Systemic
blood-pressure response to changes in rightventricular function. Circulation 28: 786, 1964.
23. FOLKOW, B.: A study of the factors influencing
the tone of denervated blood vessels perfused
at various pressures. Acta Physiol. Scand. 27:
99, 1952.
MAXWELL, G. M., ELLIOTT, R. B., AND ROBERT-
24. STAINSBY, W. N., AND RENKIN, E. M.: Auto-
SON, E.: Observations on the effect of induced
hypervolemia upon the general and coronary
haemodynamics of the intact animal. Clin.
Sci. 26: 61, 1964.
regulation of blood flow in peripheral vascular
beds. Am. J. Cardiol. 8: 741, 1961.
25.
MCMICHAEL, J., AND SHARPEY-SCHAFER,
CARRIER, O., JR., WALKER, J. R., AND GUYTON,
A. C : Oxygen autoregulation of blood flow.
Am. J. Physiol. 206: 951, 1964.
FOWLER, N. O., FRANCH, R. H., AND BLOOM, W.
L.: Hemodynamic effects of anemia with and
without plasma volume expansion. Circulation
Res. 4: 319, 1956.
13.
SANAHARA, F. A., AND BECK, L.: Cardiovascular
effects of acutely produced anemia in the
normal dog. Am. J. Physiol. ]76: 139, 1954.
A.: Adjustments of the circulatory system in
normal dogs to massive transfusions. Am. J.
Physiol. 186: 92, 1956.
AND DE WARDENER, H. E.: Red blood cell
and plasma "disappearance" during rapid
plasma volume expansion. Clin. Sci. 23: 229,
1962.
REMINGTON, J. W., AND BAKER, C. H.: Plasma
volume changes accompanying reactions to
infusion of blood plasma. Am. J. Physiol. 197:
193, 1959.
6. LEAR, H., ALLEN, T. H., AND GREGERSEN, M. I.:
26.
LEDINGHAM, J. M., AND COHEN, R. D.: The role
of the heart in the pathogenesis of renal hypertension. Lancet 2: 979, 1963.
E. P.:
27. RICHARDSON, T. Q., FERMOSO, J. D., AND GUY-
Cardiac output in man by a direct Fick method. Brit. Heart J. 6: 33, 1944.
TON, A. C : Increase in mean circulatory pressure in Goldblatt hypertension. Am. J. Physiol.
207: 751, 1964.
SCHNABEL, T. G., ELIASCH, H., THOMASSON, B.,
Circulation Research, Vol. XVIII, February 1966
Hemodynamic Consequences of Induced Changes in Blood Volume
James Conway and Miklos Gellai
Downloaded from http://circres.ahajournals.org/ by guest on June 18, 2017
Circ Res. 1966;18:190-198
doi: 10.1161/01.RES.18.2.190
Circulation Research is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231
Copyright © 1966 American Heart Association, Inc. All rights reserved.
Print ISSN: 0009-7330. Online ISSN: 1524-4571
The online version of this article, along with updated information and services, is located on the
World Wide Web at:
http://circres.ahajournals.org/content/18/2/190
Permissions: Requests for permissions to reproduce figures, tables, or portions of articles originally published in
Circulation Research can be obtained via RightsLink, a service of the Copyright Clearance Center, not the
Editorial Office. Once the online version of the published article for which permission is being requested is
located, click Request Permissions in the middle column of the Web page under Services. Further information
about this process is available in the Permissions and Rights Question and Answer document.
Reprints: Information about reprints can be found online at:
http://www.lww.com/reprints
Subscriptions: Information about subscribing to Circulation Research is online at:
http://circres.ahajournals.org//subscriptions/