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C H A P T E R 2 0

Cardiac Output, Venous Return,


and Their Regulation

Cardiac output is the quantity of blood pumped into


the aorta each minute by the heart. This is
also the quantity of blood that flows through the
circulation. Cardiac output is perhaps the most
important factor that we have to consider in rela-
tion to the circulation.
Venous return is the quantity of blood flowing
from the veins into the right atrium each minute.
The venous return and the cardiac output must equal each other except for a
few heartbeats at a time when blood is temporarily stored in or removed from
the heart and lungs.

Normal Values for Cardiac Output at Rest and


During Activity
Cardiac output varies widely with the level of activity of the body. The follow-
ing factors, among others, directly affect cardiac output: (1) the basic level of
body metabolism, (2) whether the person is exercising, (3) the persons age, and
(4) size of the body.
For young, healthy men, resting cardiac output averages about 5.6 L/min.
For women, this value is about 4.9 L/min. When one considers the factor of age
as wellbecause with increasing age, body activity diminishesthe average
cardiac output for the resting adult, in round numbers, is often stated to be
almost exactly 5 L/min.
Cardiac Index
Experiments have shown that the cardiac output increases approximately in pro-
portion to the surface area of the body.Therefore, cardiac output is frequently stated
in terms of the cardiac index, which is the cardiac output per square meter of body
surface area. The normal human being weighing 70 kilograms has a body surface
area of about 1.7 square meters, which means that the normal average cardiac index
for adults is about 3 L/min/m2 of body surface area.

Effect of Age on Cardiac Output. Figure 201 shows the cardiac output, expressed
as cardiac index, at different ages. Rising rapidly to a level greater than
4 L/min/m2 at age 10 years, the cardiac index declines to about 2.4 L/min/m2 at
age 80 years. We will see later in the chapter that the cardiac output is regu-
lated throughout life almost directly in proportion to the overall bodily meta-
bolic activity. Therefore, the declining cardiac index is indicative of declining
activity with age.

Control of Cardiac Output by Venous


ReturnRole of the Frank-Starling
Mechanism of the Heart
When one states that cardiac output is controlled by venous return, this means
that it is not the heart itself that is the primary controller of cardiac output.
232
Chapter 20 Cardiac Output, Venous Return, and Their Regulation 233

Cardiac output
35 and cardiac index

Oxygen consumption (L/min)


Cardiac output (L/min/m2)
4 4
30 Oxygen

Cardiac index (L/min/m2)


15 consumption 4
25
Cardiac index (L/min/m2 )

3 3 20 3
10
15
2
10 Dexter 1951
5 Douglas 1922
2 2 1
5 Christensen 1931
Donald 1055
0 0 0
0 200 400 600 800 1000 1200 14001600
1 1 Work output during exercise (kg-m/min)

0 0 Figure 202
0 10 20 30 40 50 60 70 80
Age in years Effect of increasing levels of exercise to increase cardiac output
(red solid line) and oxygen consumption (blue dashed line).
(Redrawn from Guyton AC, Jones CE, Coleman TB: Circulatory
Physiology: Cardiac Output and Its Regulation. 2nd ed. Philadel-
Figure 201 phia: WB Saunders Co, 1973.)

Cardiac index for the human being (cardiac output per square
meter of surface area) at different ages. (Redrawn from Guyton Under most normal unstressful conditions, the
AC, Jones CE, Coleman TB: Circulatory Physiology: Cardiac
Output and Its Regulation. 2nd ed. Philadelphia: WB Saunders Co, cardiac output is controlled almost entirely by periph-
1973.) eral factors that determine venous return. However,
we shall see later in the chapter that if the returning
blood does become more than the heart can pump,
then the heart becomes the limiting factor that deter-
mines cardiac output.
Instead, it is the various factors of the peripheral cir-
culation that affect flow of blood into the heart from
the veins, called venous return, that are the primary Cardiac Output Regulation Is the Sum
controllers.
of Blood Flow Regulation in All the
The main reason peripheral factors are usually more
important than the heart itself in controlling cardiac Local Tissues of the BodyTissue
output is that the heart has a built-in mechanism that Metabolism Regulates Most Local
normally allows it to pump automatically whatever Blood Flow
amount of blood that flows into the right atrium from
the veins. This mechanism, called the Frank-Starling The venous return to the heart is the sum of all the
law of the heart, was discussed in Chapter 9. Basically, local blood flows through all the individual tissue
this law states that when increased quantities of blood segments of the peripheral circulation. Therefore, it
flow into the heart, the increased blood stretches the follows that cardiac output regulation is the sum of all
walls of the heart chambers. As a result of the stretch, the local blood flow regulations.
the cardiac muscle contracts with increased force, and The mechanisms of local blood flow regulation were
this empties the extra blood that has entered from the discussed in Chapter 17. In most tissues, blood flow
systemic circulation. Therefore, the blood that flows increases mainly in proportion to each tissues metab-
into the heart is automatically pumped without delay olism. For instance, local blood flow almost always
into the aorta and flows again through the circulation. increases when tissue oxygen consumption increases;
Another important factor, discussed in Chapter 10, this effect is demonstrated in Figure 202 for different
is that stretching the heart causes the heart to pump levels of exercise. Note that at each increasing level of
fasterat an increased heart rate.That is, stretch of the work output during exercise, the oxygen consumption
sinus node in the wall of the right atrium has a direct and the cardiac output increase in parallel to each
effect on the rhythmicity of the node itself to increase other.
heart rate as much as 10 to 15 per cent. In addition, To summarize, cardiac output is determined by the
the stretched right atrium initiates a nervous reflex sum of all the various factors throughout the body that
called the Bainbridge reflex, passing first to the vaso- control local blood flow. All the local blood flows
motor center of the brain and then back to the heart summate to form the venous return, and the heart
by way of the sympathetic nerves and vagi, also to automatically pumps this returning blood back into
increase the heart rate. the arteries to flow around the system again.
234 Unit IV The Circulation

Removal of both arms and legs


Beriberi

Hyperthyroidism
25

AV shunts

Pulmonary disease
Pagets disease
200
Arterial pressure or cardiac output

20
Hypereffective

Hypothyroidism

Cardiac output (L/min)


(percentage of normal)

Ca

150 di
r

ac 15
Normal
Normal
Anemia

100 out
p ut 10

Hypoeffective
50
5

0
40 60 80 100 120 140 160 0
Total peripheral resistance 4 0 +4 +8
(percentage of normal) Right atrial pressure (mm Hg)

Figure 203
Figure 204
Chronic effect of different levels of total peripheral resistance on
cardiac output, showing a reciprocal relationship between total Cardiac output curves for the normal heart and for hypoeffective
peripheral resistance and cardiac output. (Redrawn from Guyton and hypereffective hearts. (Redrawn from Guyton AC, Jones CE,
AC: Arterial Pressure and Hypertension. Philadelphia: WB Coleman TB: Circulatory Physiology: Cardiac Output and Its
Saunders Co, 1980.) Regulation. 2nd ed. Philadelphia: WB Saunders Co, 1973.)

Effect of Total Peripheral Resistance on the Long-Term Cardiac


Output Level. Figure 203 is the same as Figure 195.
Figure 204 demonstrates the normal cardiac output
It is repeated here to illustrate an extremely important
curve, showing the cardiac output per minute at each
principle in cardiac output control: Under most
level of right atrial pressure. This is one type of cardiac
normal conditions, the long-term cardiac output level
function curve, which was discussed in Chapter 9. Note
varies reciprocally with changes in total peripheral
that the plateau level of this normal cardiac output
resistance. Note in Figure 203 that when the total
curve is about 13 L/min, 2.5 times the normal cardiac
peripheral resistance is exactly normal (at the 100 per
output of about 5 L/min. This means that the normal
cent mark in the figure), the cardiac output is also
human heart, functioning without any special stimula-
normal. Then, when the total peripheral resistance
tion, can pump an amount of venous return up to
increases above normal, the cardiac output falls; con-
about 2.5 times the normal venous return before the
versely, when the total peripheral resistance decreases,
heart becomes a limiting factor in the control of
the cardiac output increases. One can easily under-
cardiac output.
stand this by reconsidering one of the forms of Ohms
Shown in Figure 204 are several other cardiac
law, as expressed in Chapter 14:
output curves for hearts that are not pumping nor-
Arterial Pressure mally. The uppermost curves are for hypereffective
Cardiac Output = hearts that are pumping better than normal. The low-
Total Peripheral Resistance
ermost curves are for hypoeffective hearts that are
The meaning of this formula, and of Figure 203, is pumping at levels below normal.
simply the following: Any time the long-term level of
total peripheral resistance changes (but no other func- Factors That Can Cause Hypereffective Heart
tions of the circulation change), the cardiac output Only two types of factors usually can make the heart
changes quantitatively in exactly the opposite direction. a better pump than normal. They are (1) nervous stim-
ulation and (2) hypertrophy of the heart muscle.

The Heart Has Limits for the Cardiac Effect of Nervous Excitation to Increase Heart Pumping. In
Output That It Can Achieve Chapter 9, we saw that a combination of (1) sympa-
thetic stimulation and (2) parasympathetic inhibition
There are definite limits to the amount of blood that does two things to increase the pumping effectiveness
the heart can pump, which can be expressed quantita- of the heart: (1) it greatly increases the heart rate
tively in the form of cardiac output curves. sometimes, in young people, from the normal level of
Chapter 20 Cardiac Output, Venous Return, and Their Regulation 235
72 beats/min up to 180 to 200 beats/minand (2) it
increases the strength of heart contraction (which is
called increased contractility) to twice its normal 6
Dinitrophenol

Cardiac output
strength. Combining these two effects, maximal 5
nervous excitation of the heart can raise the plateau

(L/min)
4
level of the cardiac output curve to almost twice the 3
plateau of the normal curve, as shown by the 25-liter 2
level of the uppermost curve in Figure 204. 0
Increased Pumping Effectiveness Caused by Heart Hypertrophy. With pressure control
A long-term increased workload, but not so much Without pressure control
excess load that it damages the heart, causes the heart

Arterial pressure
muscle to increase in mass and contractile strength in 100

(mm Hg)
the same way that heavy exercise causes skeletal 75
muscles to hypertrophy. For instance, it is common for
50
the hearts of marathon runners to be increased in mass
by 50 to 75 per cent. This increases the plateau level of 0
the cardiac output curve, sometimes 60 to 100 per cent, 0 10 20 30
and therefore allows the heart to pump much greater Minutes
than usual amounts of cardiac output.
When one combines nervous excitation of the heart
and hypertrophy, as occurs in marathon runners, the
total effect can allow the heart to pump as much 30 to Figure 205
40 L/min, about 21/2 times normal; this increased level
Experiment in a dog to demonstrate the importance of nervous
of pumping is one of the most important factors in maintenance of the arterial pressure as a prerequisite for cardiac
determining the runners running time. output control. Note that with pressure control, the metabolic stim-
ulant dinitrophenol increases cardiac output greatly; without pres-
Factors That Cause a Hypoeffective Heart sure control, the arterial pressure falls and the cardiac output rises
very little. (Drawn from experiments by Dr. M. Banet.)
Any factor that decreases the hearts ability to pump
blood causes hypoeffectivity. Some of the factors that
can do this are the following: However, after autonomic control of the nervous
Coronary artery blockage, causing a heart system had been blocked, none of the normal circula-
attack tory reflexes for maintaining the arterial pressure
Inhibition of nervous excitation of the heart could function, and vasodilation of the vessels with
Pathological factors that cause abnormal heart dinitrophenol (dashed curves) then caused a profound
rhythm or rate of heartbeat fall in arterial pressure to about one half normal, and
Valvular heart disease the cardiac output rose only 1.6-fold instead of 4-fold.
Increased arterial pressure against which the Thus, maintenance of a normal arterial pressure by
heart must pump, such as in hypertension the nervous reflexes, by mechanisms explained in
Congenital heart disease Chapter 18, is essential to achieve high cardiac outputs
Myocarditis when the peripheral tissues dilate their vessels to
Cardiac hypoxia increase the venous return.

Effect of the Nervous System to Increase the Arterial Pressure


What Is the Role of the During Exercise. During exercise, intense increase in
Nervous System in Controlling metabolism in active skeletal muscles acts directly on
Cardiac Output? the muscle arterioles to relax them and to allow ade-
quate oxygen and other nutrients needed to sustain
Importance of the Nervous System in muscle contraction. Obviously, this greatly decreases
Maintaining the Arterial Pressure When the the total peripheral resistance, which normally would
Venous Return and Cardiac Output Increase decrease the arterial pressure also. However, the
Figure 205 shows an important difference in cardiac nervous system immediately compensates. The same
output control with and without a functioning auto- brain activity that sends motor signals to the muscles
nomic nervous system. The solid curves demonstrate sends simultaneous signals into the autonomic nervous
the effect in the normal dog of intense dilation of centers of the brain to excite circulatory activity,
the peripheral blood vessels caused by administering causing large vein constriction, increased heart rate,
the drug dinitrophenol, which increased the metabo- and increased contractility of the heart. All these
lism of virtually all tissues of the body about fourfold. changes acting together increase the arterial pressure
Note that with nervous control to keep the arterial above normal, which in turn forces still more blood
pressure from falling, dilating all the peripheral blood flow through the active muscles.
vessels caused almost no change in arterial pressure In summary, when local tissue vessels dilate and
but increased the cardiac output almost fourfold. thereby increase venous return and cardiac output
236 Unit IV The Circulation

above normal, the nervous system plays an exceed- and at the same time increase the cardiac output to
ingly important role in preventing the arterial pressure above normal.
from falling to disastrously low levels. In fact, during 1. Beriberi. This disease is caused by insufficient
exercise, the nervous system goes even further, pro- quantity of the vitamin thiamine (vitamin B1) in the
diet. Lack of this vitamin causes diminished ability
viding additional signals to raise the arterial pressure
of the tissues to use some cellular nutrients, and the
even above normal, which serves to increase the local tissue blood flow mechanisms in turn cause
cardiac output an extra 30 to 100 per cent. marked compensatory peripheral vasodilation.
Sometimes the total peripheral resistance decreases
to as little as one-half normal. Consequently, the
Pathologically High and long-term levels of venous return and cardiac
Pathologically Low output also often increase to twice normal.
Cardiac Outputs 2. Arteriovenous fistula (shunt). Earlier, we pointed
out that whenever a fistula (also called an AV
In healthy human beings, the cardiac outputs are shunt) occurs between a major artery and a major
surprisingly constant from one person to another. vein, tremendous amounts of blood flow directly
However, multiple clinical abnormalities can cause from the artery into the vein. This, too, greatly
either high or low cardiac outputs. Some of the more decreases the total peripheral resistance and,
important of these are shown in Figure 206. likewise, increases the venous return and cardiac
output.
3. Hyperthyroidism. In hyperthyroidism, the
High Cardiac Output Caused metabolism of most tissues of the body becomes
by Reduced Total Peripheral greatly increased. Oxygen usage increases, and
Resistance vasodilator products are released from the tissues.
Therefore, the total peripheral resistance decreases
The left side of Figure 206 identifies conditions that markedly because of the local tissue blood
commonly cause cardiac outputs higher than normal. flow control reactions throughout the body;
One of the distinguishing features of these conditions is consequently, the venous return and cardiac output
that they all result from chronically reduced total periph- often increase to 40 to 80 per cent above normal.
eral resistance. None of them result from excessive 4. Anemia. In anemia, two peripheral effects greatly
excitation of the heart itself, which we will explain sub- decrease the total peripheral resistance. One of
sequently. For the present, let us look at some of the these is reduced viscosity of the blood, resulting
conditions that can decrease the peripheral resistance from the decreased concentration of red blood

200 7

175 6

150
5
(per cent of control)

125
Cardiac output

Cardiac index

4
(L/min/m2)

Control (young adults)


100
Average 45-year-old adult
3
Control (young adults) (308)
Pulmonary disease (29)

75
Hyperthyroidism (29)

Myocardial infarction (22)


Mild valve disease (31)

Severe valve disease (29)


Pagets disease (9)

2
Traumatic shock (4)
Hypertension (47)

50
Pregnancy (46)
AV shunts (33)

Cardiac shock (7)


Mild shock (4)
Anemia (75)

Anxiety (21)
Beriberi (5)

1
25

0 0

Figure 206

Cardiac output in different pathological conditions. The numbers in parentheses indicate number of patients studied in each condition.
(Redrawn from Guyton AC, Jones CE, Coleman TB: Circulatory Physiology: Cardiac Output and Its Regulation. 2nd ed. Philadelphia:
WB Saunders Co, 1973.)
Chapter 20 Cardiac Output, Venous Return, and Their Regulation 237
cells. The other is diminished delivery of oxygen to blood flow needs of the muscles, resulting in
the tissues, which causes local vasodilation. As a decreases in skeletal muscle blood flow and cardiac
consequence, the cardiac output increases greatly. output.
Any other factor that decreases the total peripheral Regardless of the cause of low cardiac output,
resistance chronically also increases the cardiac output. whether it be a peripheral factor or a cardiac factor, if
ever the cardiac output falls below that level required
for adequate nutrition of the tissues, the person is said
Low Cardiac Output to suffer circulatory shock. This condition can be lethal
within a few minutes to a few hours. Circulatory shock
Figure 206 shows at the far right several conditions that
is such an important clinical problem that it is discussed
cause abnormally low cardiac output. These conditions
in detail in Chapter 24.
fall into two categories: (1) those abnormalities that
cause the pumping effectiveness of the heart to fall too
low and (2) those that cause venous return to fall too
low.
A More Quantitative Analysis
of Cardiac Output Regulation
Decreased Cardiac Output Caused by Cardiac Factors. When-
ever the heart becomes severely damaged, regardless Our discussion of cardiac output regulation thus far is
of the cause, its limited level of pumping may fall below adequate for understanding the factors that control
that needed for adequate blood flow to the tissues. Some cardiac output in most simple conditions. However, to
examples of this include (1) severe coronary blood vessel understand cardiac output regulation in especially
blockage and consequent myocardial infarction, (2) stressful situations, such as the extremes of exercise,
severe valvular heart disease, (3) myocarditis, (4) cardiac cardiac failure, and circulatory shock, a more complex
tamponade, and (5) cardiac metabolic derangements. quantitative analysis is presented in the following
The effects of several of these are shown on the right in sections.
Figure 206, demonstrating the low cardiac outputs that To perform the more quantitative analysis, it is nec-
result. essary to distinguish separately the two primary factors
When the cardiac output falls so low that the tissues concerned with cardiac output regulation: (1) the
throughout the body begin to suffer nutritional defi- pumping ability of the heart, as represented by cardiac
ciency, the condition is called cardiac shock. This is dis- output curves, and (2) the peripheral factors that affect
cussed fully in Chapter 22 in relation to cardiac failure. flow of blood from the veins into the heart, as repre-
sented by venous return curves. Then one can put these
Decrease in Cardiac Output Caused by Non-cardiac Peripheral curves together in a quantitative way to show how they
FactorsDecreased Venous Return. Anything that inter- interact with each other to determine cardiac output,
feres with venous return also can lead to decreased venous return, and right atrial pressure at the same time.
cardiac output. Some of these factors are the following:
1. Decreased blood volume. By far, the most
common non-cardiac peripheral factor that leads Cardiac Output Curves Used in the
to decreased cardiac output is decreased blood Quantitative Analysis
volume, resulting most often from hemorrhage.
It is clear why this condition decreases the cardiac Some of the cardiac output curves used to depict quan-
output: Loss of blood decreases the filling of the titative heart pumping effectiveness have already been
vascular system to such a low level that there is not shown in Figure 204. However, an additional set of
enough blood in the peripheral vessels to create curves is required to show the effect on cardiac output
peripheral vascular pressures high enough to push caused by changing external pressures on the outside of
the blood back to the heart. the heart, as explained in the next section.
2. Acute venous dilation. On some occasions, the
peripheral veins become acutely vasodilated. This Effect of External Pressure Outside the Heart on Cardiac Output
results most often when the sympathetic nervous Curves. Figure 207 shows the effect of changes in exter-
system suddenly becomes inactive. For instance, nal cardiac pressure on the cardiac output curve. The
fainting often results from sudden loss of normal external pressure is equal to the normal
sympathetic nervous system activity, which causes intrapleural pressure (the pressure in the chest cavity),
the peripheral capacitative vessels, especially the which is -4 mm Hg. Note in the figure that a rise in
veins, to dilate markedly. This decreases the filling intrapleural pressure, to -2 mm Hg, shifts the entire
pressure of the vascular system because the blood cardiac output curve to the right by the same amount.
volume can no longer create adequate pressure This shift occurs because to fill the cardiac chambers
in the now flaccid peripheral blood vessels. As a with blood requires an extra 2 mm Hg right atrial pres-
result, the blood pools in the vessels and does not sure to overcome the increased pressure on the outside
return to the heart. of the heart. Likewise, an increase in intrapleural pres-
3. Obstruction of the large veins. On rare occasions, sure to +2 mm Hg requires a 6 mm Hg increase in right
the large veins leading into the heart become atrial pressure from the normal -4 mm Hg, which shifts
obstructed, so that the blood in the peripheral the entire cardiac output curve 6 mm Hg to the right.
vessels cannot flow back into the heart. Some of the factors that can alter the intrapleural
Consequently, the cardiac output falls markedly. pressure and thereby shift the cardiac output curve are
4. Decreased tissue mass, especially decreased skeletal the following:
muscle mass. With normal aging or with prolonged 1. Cyclical changes of intrapleural pressure during
periods of physical inactivity, there is usually a respiration, which are about 2 mm Hg during
reduction in the size of the skeletal muscles. This, in normal breathing but can be as much as
turn, decreases the total oxygen consumption and 50 mm Hg during strenuous breathing.
238 Unit IV The Circulation

15 Hypereffectiveincreased
intrapleural pressure
mm
Cardiac output (L/min)

Hg
) Hg 15

Hg
5 e Normal
onad

m
.
5

m
m
a mp

2m

Cardiac output (L/min)


4m
iac t

2m
re =
= Card


10

+
ure =

re =
ressu

s s ure

10

essu
press
pre
u r al p

al pr
ural

5
u r al
traple

l eu r
ap le

aple

5 Hypoeffectivereduced
r ap
l (in
Intr

intrapleural pressure
I n tr

Int
ma
or

N
0
4 0 +4 +8 +12
0
Right atrial pressure (mm Hg) 4 0 +4 +8 +12
Right atrial pressure (mm Hg)

Figure 207
Figure 208
Cardiac output curves at different levels of intrapleural pressure
and at different degrees of cardiac tamponade. (Redrawn from Combinations of two major patterns of cardiac output curves
Guyton AC, Jones CE, Coleman TB: Circulatory Physiology: showing the effect of alterations in both extracardiac pressure and
Cardiac Output and Its Regulation. 2nd ed. Philadelphia: WB effectiveness of the heart as a pump. (Redrawn from Guyton AC,
Saunders Co, 1973.) Jones CE, Coleman TB: Circulatory Physiology: Cardiac Output
and Its Regulation. 2nd ed. Philadelphia: WB Saunders Co, 1973.)

2. Breathing against a negative pressure, which shifts


the curve to a more negative right atrial pressure
(to the left). three principal factors that affect venous return to the
3. Positive pressure breathing, which shifts the curve to heart from the systemic circulation. They are as follows:
the right. 1. Right atrial pressure, which exerts a backward force
4. Opening the thoracic cage, which increases the on the veins to impede flow of blood from the
intrapleural pressure to 0 mm Hg and shifts the veins into the right atrium.
cardiac output curve to the right 4 mm Hg. 2. Degree of filling of the systemic circulation
5. Cardiac tamponade, which means accumulation of (measured by the mean systemic filling pressure),
a large quantity of fluid in the pericardial cavity which forces the systemic blood toward the heart
around the heart with resultant increase in external (this is the pressure measured everywhere in the
cardiac pressure and shifting of the curve to the systemic circulation when all flow of blood is
right. Note in Figure 207 that cardiac tamponade stoppedwe discuss this in detail later).
shifts the upper parts of the curves farther to the 3. Resistance to blood flow between the peripheral
right than the lower parts because the external vessels and the right atrium.
tamponade pressure rises to higher values as the These factors can all be expressed quantitatively
chambers of the heart fill to increased volumes by the venous return curve, as we explain in the next
during high cardiac output. sections.

Normal Venous Return Curve


Combinations of Different Patterns of Cardiac Output Curves.
Figure 208 shows that the final cardiac output curve can In the same way that the cardiac output curve relates
change as a result of simultaneous changes in (a) exter- pumping of blood by the heart to right atrial pressure,
nal cardiac pressure and (b) effectiveness of the heart as the venous return curve relates venous return also to
a pump. Thus, by knowing what is happening to the right atrial pressurethat is, the venous flow of blood
external pressure as well as to the capability of the heart into the heart from the systemic circulation at different
as a pump, one can express the momentary ability of the levels of right atrial pressure.
heart to pump blood by a single cardiac output curve. The curve in Figure 209 is the normal venous return
curve. This curve shows that when heart pumping capa-
bility becomes diminished and causes the right atrial
Venous Return Curves pressure to rise, the backward force of the rising atrial
pressure on the veins of the systemic circulation
There remains the entire systemic circulation that must decreases venous return of blood to the heart. If all
be considered before total analysis of cardiac regulation nervous circulatory reflexes are prevented from acting,
can be achieved. To analyze the function of the systemic venous return decreases to zero when the right atrial
circulation, we first remove the heart and lungs from the pressure rises to about +7 mm Hg. Such a slight rise in
circulation of an animal and replace them with a pump right atrial pressure causes a drastic decrease in venous
and artificial oxygenator system. Then, different factors, return because the systemic circulation is a distensible
such blood volume, vascular resistances, and central bag, so that any increase in back pressure causes blood
venous pressure in the right atrium, are altered to to dam up in this bag instead of returning to the heart.
determine how the systemic circulation operates in At the same time that the right atrial pressure is rising
different circulatory states. In these studies, one finds and causing venous stasis, pumping by the heart also
Chapter 20 Cardiac Output, Venous Return, and Their Regulation 239

Plateau Transitional zone

Venous return (L/min)


5 Mean
Do systemic
wn
slo filling
Figure 209 pe
pressure
Normal venous return curve. The
plateau is caused by collapse of
the large veins entering the chest
when the right atrial pressure falls 0
8 4 0 +4 +8
below atmospheric pressure.
Note also that venous return Right atrial pressure (mm Hg)
becomes zero when the right
atrial pressure rises to equal the
mean systemic filling pressure.

approaches zero because of decreasing venous return.


Both the arterial and the venous pressures come to
equilibrium when all flow in the systemic circulation
ceases at a pressure of 7 mm Hg, which, by definition, is Strong sympathetic
the mean systemic filling pressure (Psf). 14 stimulation

Mean circulatory filling pressure (mm Hg)


Normal circulatory
Plateau in the Venous Return Curve at Negative Atrial 12
system
PressuresCaused by Collapse of the Large Veins. When the Complete sympathetic
right atrial pressure falls below zerothat is, below inhibition
atmospheric pressurefurther increase in venous 10
Normal volume
return almost ceases. And by the time the right atrial
pressure has fallen to about -2 mm Hg, the venous 8
return will have reached a plateau. It remains at this
plateau level even though the right atrial pressure falls 6
to -20 mm Hg, -50 mm Hg, or even further.This plateau
is caused by collapse of the veins entering the chest. Neg- 4
ative pressure in the right atrium sucks the walls of the
veins together where they enter the chest, which pre-
2
vents any additional flow of blood from the peripheral
veins. Consequently, even very negative pressures in the
right atrium cannot increase venous return significantly 0
0 1000 2000 3000 4000 5000 6000 7000
above that which exists at a normal atrial pressure of
Volume (ml)
0 mm Hg.

Mean Circulatory Filling Pressure and Mean Systemic Filling


Pressure, and Their Effect on Venous Return
Figure 2010
When heart pumping is stopped by shocking the heart
with electricity to cause ventricular fibrillation or is Effect of changes in total blood volume on the mean circulatory
stopped in any other way, flow of blood everywhere in filling pressure (i.e., volume-pressure curves for the entire cir-
the circulation ceases a few seconds later.Without blood culatory system). These curves also show the effects of strong
flow, the pressures everywhere in the circulation sympathetic stimulation and complete sympathetic inhibition.
become equal. This equilibrated pressure level is called
the mean circulatory filling pressure.
Effect of Sympathetic Nervous Stimulation of the Circulation on
Effect of Blood Volume on Mean Circulatory Filling Pressure. Mean Circulatory Filling Pressure. The green curve and blue
The greater the volume of blood in the circulation, the curve in Figure 2010 show the effects, respectively,
greater is the mean circulatory filling pressure because of high and low levels of sympathetic nervous activity
extra blood volume stretches the walls of the vascula- on the mean circulatory filling pressure. Strong sympa-
ture. The red curve in Figure 2010 shows the approxi- thetic stimulation constricts all the systemic blood
mate normal effect of different levels of blood volume vessels as well as the larger pulmonary blood vessels
on the mean circulatory filling pressure. Note that at a and even the chambers of the heart. Therefore, the
blood volume of about 4000 milliliters, the mean circu- capacity of the system decreases, so that at each level of
latory filling pressure is close to zero because this is the blood volume, the mean circulatory filling pressure is
unstressed volume of the circulation, but at a volume increased. At normal blood volume, maximal sympa-
of 5000 milliliters, the filling pressure is the normal value thetic stimulation increases the mean circulatory filling
of 7 mm Hg. Similarly, at still higher volumes, the mean pressure from 7 mm Hg to about 2.5 times that value, or
circulatory filling pressure increases almost linearly. about 17 mm Hg.
240 Unit IV The Circulation

Conversely, complete inhibition of the sympathetic Conversely, the lower the mean systemic filling pressure,
nervous system relaxes both the blood vessels and the the more the curve shifts downward and to the left.
heart, decreasing the mean circulatory filling pressure To express this another way, the greater the system is
from the normal value of 7 mm Hg down to about 4 mm filled, the easier it is for blood to flow into the heart.
Hg. Before leaving Figure 2010, note specifically how The less the filling, the more difficult it is for blood to
steep the curves are.This means that even slight changes flow into the heart.
in blood volume or slight changes in the capacity of the
system caused by various levels of sympathetic activity
can have large effects on the mean circulatory filling Pressure Gradient for Venous ReturnWhen This Is Zero, There
pressure. Is No Venous Return. When the right atrial pressure rises
to equal the mean systemic filling pressure, there is no
Mean Systemic Filling Pressure and Its Relation to Mean Circula- longer any pressure difference between the peripheral
tory Filling Pressure. The mean systemic filling pressure, vessels and the right atrium. Consequently, there can no
Psf, is slightly different from the mean circulatory filling longer be any blood flow from any peripheral vessels
pressure. It is the pressure measured everywhere in the back to the right atrium. However, when the right atrial
systemic circulation after blood flow has been stopped pressure falls progressively lower than the mean sys-
by clamping the large blood vessels at the heart, so that temic filling pressure, the flow to the heart increases
the pressures in the systemic circulation can be meas- proportionately, as one can see by studying any of the
ured independently from those in the pulmonary circu- venous return curves in Figure 2011. That is, the greater
lation. The mean systemic pressure, although almost the difference between the mean systemic filling pressure
impossible to measure in the living animal, is the impor- and the right atrial pressure, the greater becomes the
tant pressure for determining venous return. The mean venous return. Therefore, the difference between these
systemic filling pressure, however, is almost always nearly two pressures is called the pressure gradient for venous
equal to the mean circulatory filling pressure because the return.
pulmonary circulation has less than one eighth as much
capacitance as the systemic circulation and only about
one tenth as much blood volume.
Resistance to Venous Return
In the same way that mean systemic filling pressure rep-
Effect on the Venous Return Curve of Changes in Mean Systemic
resents a pressure pushing venous blood from the
Filling Pressure. Figure 2011 shows the effects on the
periphery toward the heart, there is also resistance to
venous return curve caused by increasing or decreasing
this venous flow of blood. It is called the resistance to
the mean systemic filling pressure (Psf). Note in Figure
venous return. Most of the resistance to venous return
2011 that the normal mean systemic filling pressure is
occurs in the veins, although some occurs in the arteri-
7 mm Hg. Then, for the uppermost curve in the figure,
oles and small arteries as well.
the mean systemic filling pressure has been increased to
Why is venous resistance so important in determin-
14 mm Hg, and for the lowermost curve, has been
ing the resistance to venous return? The answer is that
decreased to 3.5 mm Hg. These curves demonstrate that
when the resistance in the veins increases, blood begins
the greater the mean systemic filling pressure (which
to be dammed up, mainly in the veins themselves. But
also means the greater the tightness with which the
the venous pressure rises very little because the veins
circulatory system is filled with blood) the more the
are highly distensible. Therefore, this rise in venous
venous return curve shifts upward and to the right.
pressure is not very effective in overcoming the resist-
ance, and blood flow into the right atrium decreases
drastically. Conversely, when arteriolar and small artery
resistances increase, blood accumulates in the arteries,
which have a capacitance only 1/30 as great as that of
the veins. Therefore, even slight accumulation of blood
in the arteries raises the pressure greatly30 times as
Venous return (L/min)

10 much as in the veinsand this high pressure does over-


Psf = 3.5 come much of the increased resistance. Mathematically,
Psf = 7 it turns out that about two thirds of the so-called resist-
5 No Psf = 14 ance to venous return is determined by venous resist-
rm
al ance, and about one third by the arteriolar and small
artery resistance.
Venous return can be calculated by the following
0 formula:
4 0 +4 +8 +12
Right atrial pressure (mm Hg)
Psf - PRA
VR =
RVR

in which VR is venous return, Psf is mean systemic


Figure 2011 filling pressure, PRA is right atrial pressure, and RVR
is resistance to venous return. In the healthy human
Venous return curves showing the normal curve when the mean
systemic filling pressure (Psf) is 7 mm Hg, and showing the effect
adult, the values for these are as follows: venous return
of altering the Psf to either 3.5 or 14 mm Hg. (Redrawn from equals 5 L/min, mean systemic filling pressure equals
Guyton AC, Jones CE, Coleman TB: Circulatory Physiology: 7 mm Hg, right atrial pressure equals 0 mm Hg, and
Cardiac Output and Its Regulation. 2nd ed. Philadelphia: WB resistance to venous return equals 1.4 mm Hg per liter
Saunders Co, 1973.) of blood flow.
Chapter 20 Cardiac Output, Venous Return, and Their Regulation 241

20 Normal resistance
15 2 resistance
1/2 resistance
1/3 resistance

Venous return (L/min)


15
Venous return (L/min)

10

1/
10 2
re
sis
ta 5
nc Psf = 10.5
Norm e Psf = 10
al r
es
5 ista
nc Psf = 7 Psf = 2.3
2 resist e Psf = 7
ance 0
4 0 +4 +8 +12
Right atrial pressure (mm Hg)
0
4 0 +4 +8
Right atrial pressure (mm Hg)
Figure 2013

Combinations of the major patterns of venous return curves,


Figure 2012 showing the effects of simultaneous changes in mean systemic
filling pressure (Psf) and in resistance to venous return.
Venous return curves depicting the effect of altering the resist- (Redrawn from Guyton AC, Jones CE, Coleman TB: Circulatory
ance to venous return. Psf, mean systemic filling pressure. Physiology: Cardiac Output and Its Regulation. 2nd ed. Philadel-
(Redrawn from Guyton AC, Jones CE, Coleman TB: Circulatory phia: WB Saunders Co, 1973.)
Physiology: Cardiac Output and Its Regulation. 2nd ed. Philadel-
phia: WB Saunders Co, 1973.)
equal the cardiac output from the heart and (2) the right
atrial pressure is the same for both the heart and the
Effect of Resistance to Venous Return on the Venous Return systemic circulation.
Curve. Figure 2012 demonstrates the effect of different Therefore, one can predict the cardiac output and
levels of resistance to venous return on the venous right atrial pressure in the following way: (1) Determine
return curve, showing that a decrease in this resistance the momentary pumping ability of the heart and depict
to one-half normal allows twice as much flow of blood this in the form of a cardiac output curve; (2) determine
and, therefore, rotates the curve upward to twice as great the momentary state of flow from the systemic circula-
a slope. Conversely, an increase in resistance to twice tion into the heart and depict this in the form of a
normal rotates the curve downward to one-half as great venous return curve; and (3) equate these curves
a slope. against each other, as shown in Figure 2014.
Note also that when the right atrial pressure rises to Two curves in the figure depict the normal cardiac
equal the mean systemic filling pressure, venous return output curve (red line) and the normal venous return
becomes zero at all levels of resistance to venous return curve (blue line). There is only one point on the graph,
because when there is no pressure gradient to cause point A, at which the venous return equals the cardiac
flow of blood, it makes no difference what the resistance output and at which the right atrial pressure is the same
is in the circulation; the flow is still zero. Therefore, the for both the heart and the systemic circulation. There-
highest level to which the right atrial pressure can rise, fore, in the normal circulation, the right atrial pressure,
regardless of how much the heart might fail, is equal to cardiac output, and venous return are all depicted by
the mean systemic filling pressure. point A, called the equilibrium point, giving a normal
value for cardiac output of 5 liters per minute and a
Combinations of Venous Return Curve Patterns. Figure 2013 right atrial pressure of 0 mm Hg .
shows effects on the venous return curve caused by
simultaneous changes in mean systemic pressure (Psf) Effect of Increased Blood Volume on Cardiac Output. A sudden
and resistance to venous return, demonstrating that increase in blood volume of about 20 per cent increases
both these factors can operate simultaneously. the cardiac output to about 2.5 to 3 times normal. An
analysis of this effect is shown in Figure 2014. Imme-
diately on infusing the large quantity of extra blood, the
Analysis of Cardiac Output and increased filling of the system causes the mean systemic
Right Atrial Pressure, Using filling pressure (Psf) to increase to 16 mm Hg, which
Simultaneous Cardiac Output and shifts the venous return curve to the right. At the same
Venous Return Curves time, the increased blood volume distends the blood
vessels, thus reducing their resistance and thereby
In the complete circulation, the heart and the systemic reducing the resistance to venous return, which rotates
circulation must operate together. This means that (1) the curve upward. As a result of these two effects, the
the venous return from the systemic circulation must venous return curve of Figure 2014 is shifted to the
242 Unit IV The Circulation

Cardiac output and venous return (L/min)

25

Cardiac output and venous return (L/min)


20 Maximal sympathetic
stimulation
Moderate sympathetic
20 stimulation
15
B Normal
Spinal anesthesia
15
10

10 D
5 A Psf = 7 Psf = 16
C
A
5
0
4 0 +4 +8 +12 +16 B
Right atrial pressure (mm Hg) 0
4 0 +4 +8 +12 +16
Right atrial pressure (mm Hg)

Figure 2014

The two solid curves demonstrate an analysis of cardiac output Figure 2015
and right atrial pressure when the cardiac output (red line) and
venous return (blue line) curves are normal. Transfusion of blood Analysis of the effect on cardiac output of (1) moderate sympa-
equal to 20 per cent of the blood volume causes the venous return thetic stimulation (from point A to point C), (2) maximal sympa-
curve to become the dashed curve; as a result, the cardiac output thetic stimulation (point D), and (3) sympathetic inhibition caused
and right atrial pressure shift from point A to point B. Psf, mean by total spinal anesthesia (point B). (Redrawn from Guyton AC,
systemic filling pressure. Jones CE, Coleman TB: Circulatory Physiology: Cardiac Output
and Its Regulation. 2nd ed. Philadelphia: WB Saunders Co, 1973.)

right. This new curve equates with the cardiac output each other at point A, which represents a normal venous
curve at point B, showing that the cardiac output and return and cardiac output of 5 L/min and a right atrial
venous return increase 2.5 to 3 times, and that the right pressure of 0 min Hg. Note in the figure that maximal
atrial pressure rises to about +8 mm Hg. sympathetic stimulation (green curves) increases the
mean systemic filling pressure to 17 mm Hg (depicted
Further Compensatory Effects Initiated in Response to Increased by the point at which the venous return curve reaches
Blood Volume. The greatly increased cardiac output the zero venous return level).And the sympathetic stim-
caused by increased blood volume lasts for only a few ulation also increases pumping effectiveness of the
minutes because several compensatory effects immedi- heart by nearly 100 per cent. As a result, the cardiac
ately begin to occur: (1) The increased cardiac output output rises from the normal value at equilibrium point
increases the capillary pressure so that fluid begins to A to about double normal at equilibrium point Dand
transude out of the capillaries into the tissues, thereby yet the right atrial pressure hardly changes. Thus, differ-
returning the blood volume toward normal. (2) The ent degrees of sympathetic stimulation can increase the
increased pressure in the veins causes the veins to cardiac output progressively to about twice normal for
continue distending gradually by the mechanism called short periods of time, until other compensatory effects
stress-relaxation, especially causing the venous blood occur within seconds or minutes.
reservoirs, such as the liver and spleen, to distend, thus Effect of Sympathetic Inhibition on Cardiac Output. The sym-
reducing the mean systemic pressure. (3) The excess pathetic nervous system can be blocked by inducing
blood flow through the peripheral tissues causes total spinal anesthesia or by using some drug, such as
autoregulatory increase in the peripheral resistance, hexamethonium, that blocks transmission of nerve
thus increasing the resistance to venous return. These signals through the autonomic ganglia. The lowermost
factors cause the mean systemic filling pressure to curves in Figure 2015 show the effect of sympathetic
return back toward normal and the resistance vessels of inhibition caused by total spinal anesthesia, demon-
the systemic circulation to constrict. Therefore, gradu- strating that (1) the mean systemic filling pressure falls
ally, over a period of 10 to 40 minutes, the cardiac output to about 4 mm Hg and (2) the effectiveness of the heart
returns almost to normal. as a pump decreases to about 80 per cent of normal. The
cardiac output falls from point A to point B, which is a
Effect of Sympathetic Stimulation on Cardiac Output. Sympa- decrease to about 60 per cent of normal.
thetic stimulation affects both the heart and the sys-
temic circulation: (1) It makes the heart a stronger pump. Effect of Opening a Large Arteriovenous Fistula. Figure 2016
(2) In the systemic circulation, it increases the mean shows various stages of circulatory changes that occur
systemic filling pressure because of contraction of after opening a large arteriovenous fistula, that is, after
the peripheral vesselsespecially the veinsand it making an opening directly between a large artery and
increases the resistance to venous return. a large vein.
In Figure 2015, the normal cardiac output and 1. The two red curves crossing at point A show the
venous return curves are depicted; these equate with normal condition.
Chapter 20 Cardiac Output, Venous Return, and Their Regulation 243

D
20
20

Flow (L/min)
Cardiac output and venous return (L/min)

15
C 10
15 5
B 0

0 1 2
10 Seconds

5
A Figure 2017

Pulsatile blood flow in the root of the aorta recorded using an elec-
tromagnetic flowmeter.

0
4 0 +4 +8 +12
Right atrial pressure (mm Hg) 4. Point D shows the effect after several more weeks.
By this time, the blood volume has increased
because the slight reduction in arterial pressure and
the sympathetic stimulation have both reduced
Figure 2016 kidney output of urine. The mean systemic filling
pressure has now risen to +12 mm Hg, shifting the
Analysis of successive changes in cardiac output and right atrial venous return curve another 3 mm Hg to the right.
pressure in a human being after a large arteriovenous (AV) fistula Also, the prolonged increased workload on the
is suddenly opened. The stages of the analysis, as shown by the
equilibrium points, are A, normal conditions; B, immediately after
heart has caused the heart muscle to hypertrophy
opening the AV fistula; C, 1 minute or so after the sympathetic slightly, raising the level of the cardiac output curve
reflexes have become active; and D, several weeks after the blood still further. Therefore, point D shows a cardiac
volume has increased and the heart has begun to hypertrophy. output now of almost 20 L/min and a right atrial
(Redrawn from Guyton AC, Jones CE, Coleman TB: Circulatory pressure of about 6 mm Hg.
Physiology: Cardiac Output and Its Regulation. 2nd ed. Philadel-
phia: WB Saunders Co, 1973.) Other Analyses of Cardiac Output Regulation. In Chapter 21,
analysis of cardiac output regulation during exercise is
presented, and in Chapter 22, analyses of cardiac output
regulation at various stages of congestive heart failure
2. The curves crossing at point B show the circulatory are shown.
condition immediately after opening the large
fistula. The principal effects are (1) a sudden and
precipitous rotation of the venous return curve Methods for Measuring
upward caused by the large decrease in resistance to Cardiac Output
venous return when blood is allowed to flow with
almost no impediment directly from the large In animal experiments, one can cannulate the aorta, pul-
arteries into the venous system, bypassing most monary artery, or great veins entering the heart and
of the resistance elements of the peripheral measure the cardiac output using any type of flowme-
circulation, and (2) a slight increase in the level of ter. An electromagnetic or ultrasonic flowmeter can also
the cardiac output curve because opening the fistula be placed on the aorta or pulmonary artery to measure
decreases the peripheral resistance and allows cardiac output.
an acute fall in arterial pressure against which In the human, except in rare instances, cardiac output
the heart can pump more easily. The net result, is measured by indirect methods that do not require
depicted by point B, is an increase in cardiac output surgery. Two of the methods commonly used are the
from 5 L/min up to 13 L/min and an increase in oxygen Fick method and the indicator dilution method.
right atrial pressure to about +3 mm Hg.
3. Point C represents the effects about 1 minute later,
after the sympathetic nerve reflexes have restored Pulsatile Output of the Heart as
the arterial pressure almost to normal and caused Measured by an Electromagnetic or
two other effects: (1) an increase in the mean Ultrasonic Flowmeter
systemic filling pressure (because of constriction of
all veins and arteries) from 7 to 9 mm Hg, thus Figure 2017 shows a recording in a dog of blood flow
shifting the venous return curve 2 mm Hg to the in the root of the aorta made using an electromagnetic
right, and (2) further elevation of the cardiac flowmeter. It demonstrates that the blood flow rises
output curve because of sympathetic nervous rapidly to a peak during systole, and then at the end of
excitation of the heart. The cardiac output now systole reverses for a fraction of a second. This reverse
rises to almost 16 L/min, and the right atrial flow causes the aortic valve to close and the flow to
pressure to about 4 mm Hg. return to zero.
244 Unit IV The Circulation

Measurement of Cardiac Output Using Indicator Dilution Method for


the Oxygen Fick Principle Measuring Cardiac Output
To measure cardiac output by the so-called indicator
The Fick principle is explained by Figure 2018. This dilution method, a small amount of indicator, such as
figure shows that 200 milliliters of oxygen are being a dye, is injected into a large systemic vein or, prefer-
absorbed from the lungs into the pulmonary blood ably, into the right atrium. This passes rapidly through
each minute. It also shows that the blood entering the the right side of the heart, then through the blood
right heart has an oxygen concentration of 160 milli- vessels of the lungs, through the left side of the heart
liters per liter of blood, whereas that leaving the left and, finally, into the systemic arterial system. The con-
heart has an oxygen concentration of 200 milliliters centration of the dye is recorded as the dye passes
per liter of blood. From these data, one can calculate through one of the peripheral arteries, giving a curve as
that each liter of blood passing through the lungs shown in Figure 2019. In each of these instances, 5 mil-
ligrams of Cardio-Green dye was injected at zero time.
absorbs 40 milliliters of oxygen.
In the top recording, none of the dye passed into the
Because the total quantity of oxygen absorbed into arterial tree until about 3 seconds after the injection, but
the blood from the lungs each minute is 200 milliliters, then the arterial concentration of the dye rose rapidly
dividing 200 by 40 calculates a total of five 1-liter por- to a maximum in about 6 to 7 seconds. After that, the
tions of blood that must pass through the pulmonary concentration fell rapidly, but before the concentration
circulation each minute to absorb this amount of reached zero, some of the dye had already circulated all
oxygen. Therefore, the quantity of blood flowing the way through some of the peripheral systemic vessels
through the lungs each minute is 5 liters, which is also and returned through the heart for a second time. Con-
a measure of the cardiac output. Thus, the cardiac sequently, the dye concentration in the artery began to
output can be calculated by the following formula: rise again. For the purpose of calculation, it is necessary
to extrapolate the early down-slope of the curve to the
Cardiac output (L min) zero point, as shown by the dashed portion of each
curve. In this way, the extrapolated time-concentration
O2 absorbed per minute by the lungs (ml min) curve of the dye in the systemic artery without recircu-
=
Arteriovenous O2 difference (ml L of blood) lation can be measured in its first portion and estimated
reasonably accurately in its latter portion.
In applying this Fick procedure for measuring Once the extrapolated time-concentration curve has
cardiac output in the human being, mixed venous been determined, one then calculates the mean con-
blood is usually obtained through a catheter inserted centration of dye in the arterial blood for the duration
up the brachial vein of the forearm, through the sub- of the curve. For instance, in the top example of Figure
clavian vein, down to the right atrium, and, finally, into 2019, this was done by measuring the area under the
the right ventricle or pulmonary artery. And systemic
arterial blood can then be obtained from any systemic
artery in the body. The rate of oxygen absorption by
the lungs is measured by the rate of disappearance of
oxygen from the respired air, using any type of oxygen 5 mg
meter. injected

0.5
Dye concentration in artery (mg/dl)

0.4
0.3
0.2
0.1
0
LUNGS 0 10 20 30
5 mg
0.5 injected
Oxygen used = 200 ml/min 0.4
0.3
0.2
0.1
0
Cardiac output = 0 10 20 30
O2 = 5000 ml/min O2 =
Seconds
160 ml/L 200 ml/L
right heart left heart

Figure 2019

Extrapolated dye concentration curves used to calculate two sep-


Figure 2018 arate cardiac outputs by the dilution method. (The rectangular
areas are the calculated average concentrations of dye in the arte-
Fick principle for determining cardiac output. rial blood for the durations of the respective extrapolated curves.)
Chapter 20 Cardiac Output, Venous Return, and Their Regulation 245
entire initial and extrapolated curve and then averaging Guyton AC: Venous return. In: Hamilton WF (ed): Hand-
the concentration of dye for the duration of the curve; book of Physiology. Sec 2, Vol. 2. Baltimore, Williams &
one can see from the shaded rectangle straddling the Wilkins, 1963, p 1099.
curve in the upper figure that the average concentration Guyton AC: Determination of cardiac output by equating
of dye was 0.25 mg/dl of blood and that the duration venous return curves with cardiac response curves. Physiol
of this average value was 12 seconds. A total of 5 mil- Rev 35:123, 1955.
ligrams of dye had been injected at the beginning of the Guyton AC, Coleman TG, Granger HJ: Circulation: overall
experiment. For blood carrying only 0.25 milligram of regulation. Annu Rev Physiol 34:13, 1972.
dye in each deciliter to carry the entire 5 milligrams of Guyton AC, Jones CE, Coleman TG: Circulatory Physiology:
dye through the heart and lungs in 12 seconds, a total Cardiac Output and Its Regulation. Philadelphia: WB
of 20 1-deciliter portions of blood would have passed Saunders Co, 1973.
through the heart during the 12 seconds, which would Guyton AC, Lindsey AW, Kaufmann BN: Effect of mean cir-
be the same as a cardiac output of 2 L/12 sec, or culatory filling pressure and other peripheral circulatory
10 L/min. We leave it to the reader to calculate the factors on cardiac output. Am J Physiol 180:463-468, 1955.
cardiac output from the bottom extrapolated curve of Koch WJ, Lefkowitz RJ, Rockman HA: Functional conse-
Figure 2019. To summarize, the cardiac output can be quences of altering myocardial adrenergic receptor sig-
determined using the following formula: naling. Annu Rev Physiol 62:237, 2000.
Rockman HA, Koch WJ, Lefkowitz RJ: Seven-transmem-
Cardiac output (ml min) = brane-spanning receptors and heart function. Nature
415:206, 2002.
Milligrams of dye injected 60 Rothe CF: Mean circulatory filling pressure: its meaning and
Average concentration of dye Duration of measurement. J Appl Physiol 74:499, 1993.
in each milliliter of blood the curve Rothe CF: Reflex control of veins and vascular capacitance.
for the duration of the curve in seconds Physiol Rev 63:1281, 1983.
Sarnoff SJ, Berglund E: Ventricular function. 1. Starlings law
of the heart, studied by means of simultaneous right and
left ventricular function curves in the dog. Circulation
References 9:706-718, 1953.
Uemura K, Sugimachi M, Kawada T, et al: A novel frame-
Brengelmann GL: A critical analysis of the view that right work of circulatory equilibrium. Am J Physiol Heart Circ
atrial pressure determines venous return. J Appl Physiol Physiol 286:H2376, 2004.
94:849, 2003. Vatner SF, Braunwald E: Cardiovascular control mecha-
Gaasch WH, Zile MR: Left ventricular diastolic dysfunction nisms in the conscious state. N Engl J Med 293:970, 1975.
and diastolic heart failure. Annu Rev Med. 55:373, 2004.

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