Cardiac Output and Venous Return and Their Regulation pdf - The Circulation

When one states that cardiac output is controlled by venous return, this means

Mechanism of the Heart

Return—Role of the Frank-Starling

Control of Cardiac Output by Venous

activity with age.

bolic activity. Therefore, the declining cardiac index is indicative of declining

age 80 years. We will see later in the chapter that the cardiac output is regu-

at age 10 years, the cardiac index declines to about 2.4 L/min/m

as cardiac index, at different ages. Rising rapidly to a level greater than

Figure 20–1 shows the cardiac output, expressed

area of about 1.7 square meters, which means that the normal average cardiac index

The normal human being weighing 70 kilograms has a body surface

cardiac output per square meter of body

, which is the

cardiac index

portion to the surface area of the body. Therefore, cardiac output is frequently stated

cardiac output for the resting adult, in round numbers, is often stated to be

as well—because with increasing age, body activity diminishes—the average

, this value is about 4.9 L/min. When one considers the factor of age

For

, resting cardiac output averages about 5.6 L/min.

For

(4) size of the body.

body metabolism, (2) whether the person is exercising, (3) the person’s age, and

ing factors, among others, directly affect cardiac output: (1) the basic level of

Cardiac output varies widely with the level of activity of the body. The follow-

Normal Values for Cardiac Output at Rest and

the heart and lungs.

The venous return and the cardiac output must equal each other except for a

from the veins into the right atrium each minute.

Venous return

circulation. Cardiac output is perhaps the most

the aorta each minute by the heart. This is

Cardiac output

and Their Regulation

Cardiac Output, Venous Return,

232

is the quantity of blood pumped into

also the quantity of blood that flows through the

important factor that we have to consider in rela-
tion to the circulation.

is the quantity of blood flowing

few heartbeats at a time when blood is temporarily stored in or removed from

During Activity

young, healthy men

women

almost exactly 5 L/min.

Cardiac Index

Experiments have shown that the cardiac output increases approximately in pro-

in terms of the
surface area.

for adults is about 3 L/min/m

of body surface area.

Effect of Age on Cardiac Output.

4 L/min/m

lated throughout life almost directly in proportion to the overall bodily meta-

that it is not the heart itself that is the primary controller of cardiac output.

summate to form the venous return, and the heart

control local blood flow. All the local blood flows

To summarize, cardiac output is determined by the

other.

work output during exercise, the oxygen consumption

levels of exercise. Note that at each increasing level of

this effect is demonstrated in Figure 20–2 for different

olism. For instance, local blood flow almost always

increases mainly in proportion to each tissue’s metab-

discussed in Chapter 17. In most tissues, blood flow

The mechanisms of local blood flow regulation were

the local blood flow regulations.

segments of the peripheral circulation. Therefore, it

The venous return to the heart is the sum of all the

Metabolism Regulates Most Local

Local Tissues of the Body—Tissue

of Blood Flow Regulation in All the

Cardiac Output Regulation Is the Sum

blood does become more than the heart can pump,

eral factors that determine venous return. However,

Under most normal unstressful conditions,

increase the heart rate.

by way of the sympathetic nerves and vagi, also to

, passing first to the vaso-

heart rate as much as 10 to 15 per cent. In addition,

faster—at an increased heart rate.That is, stretch of the

Another important factor, discussed in Chapter 10,

systemic circulation. Therefore, the blood that flows

the cardiac muscle contracts with increased force, and

walls of the heart chambers. As a result of the stretch,

flow into the heart, the increased blood stretches the

, was discussed in Chapter 9. Basically,

Frank-Starling

the veins. This mechanism, called the

The main reason peripheral factors are usually more

controllers.

, that are the primary

the veins, called

Instead, it is the various factors of the peripheral cir-

Cardiac Output, Venous Return, and Their Regulation

Chapter 20

233

culation that affect flow of blood into the heart from

venous return

important than the heart itself in controlling cardiac
output is that the heart has a built-in mechanism that
normally allows it to pump automatically whatever
amount of blood that flows into the right atrium from

law of the heart
this law states that when increased quantities of blood

this empties the extra blood that has entered from the

into the heart is automatically pumped without delay
into the aorta and flows again through the circulation.

is that stretching the heart causes the heart to pump

sinus node in the wall of the right atrium has a direct
effect on the rhythmicity of the node itself to increase

the stretched right atrium initiates a nervous reflex
called the Bainbridge reflex
motor center of the brain and then back to the heart

the

cardiac output is controlled almost entirely by periph-

we shall see later in the chapter that if the returning

then the heart becomes the limiting factor that deter-
mines cardiac output.

Blood Flow

local blood flows through all the individual tissue

follows that cardiac output regulation is the sum of all

increases when tissue oxygen consumption increases;

and the cardiac output increase in parallel to each

sum of all the various factors throughout the body that

automatically pumps this returning blood back into
the arteries to flow around the system again.

Cardiac index (L

/min

)

Age in years

AC, Jones CE, Coleman TB: Circulatory Physiology: Cardiac

meter of surface area) at different ages. (Redrawn from Guyton

for the human being (cardiac output per square

Cardiac index

Figure 20–1

Output and Its Regulation. 2nd ed. Philadelphia: WB Saunders Co,
1973.)

Work output during exercise (kg-m/min)

200 400 600 800 1000 1200 14001600

Oxygen consumption (L

/min)

Cardiac output (L

/min

Cardiac index (L

/min

)

Cardiac output
and cardiac index

Oxygen
consumption

Dexter
Douglas
Christensen
Donald

1951
1922
1931
1055

Physiology: Cardiac Output and Its Regulation. 2nd ed. Philadel-

(Redrawn from Guyton AC, Jones CE, Coleman TB: Circulatory

(red solid line)

Effect of increasing levels of exercise to increase cardiac output

Figure 20–2

and oxygen consumption (blue dashed line).

phia: WB Saunders Co, 1973.)

cardiac output curves

the heart can pump, which can be expressed quantita-

There are definite limits to the amount of blood that

Output That It Can Achieve

tions of the circulation change), the cardiac output

simply the following: Any time the long-term level of

The meaning of this formula, and of Figure 20–3, is

law, as expressed in Chapter 14:

stand this by reconsidering one of the forms of Ohm’s

the cardiac output increases. One can easily under-

versely, when the total peripheral resistance decreases,

increases above normal, the cardiac output falls; con-

normal. Then, when the total peripheral resistance

cent mark in the figure), the cardiac output is also

resistance. Note in Figure 20–3 that when the total

normal conditions, the long-term cardiac output level

principle in cardiac output control: Under most

Figure 20–3 is the same as Figure 19–5.

Effect of Total Peripheral Resistance on the Long-Term Cardiac

234

Unit IV

The Circulation

Output Level.

It is repeated here to illustrate an extremely important

varies reciprocally with changes in total peripheral

peripheral resistance is exactly normal (at the 100 per

total peripheral resistance changes (but no other func-

changes quantitatively in exactly the opposite direction.

The Heart Has Limits for the Cardiac

tively in the form of

Cardiac Output

Arterial Pressure

Total Peripheral Resistance

sometimes, in young people, from the normal level of

of the heart: (1) it greatly increases the heart rate

Chapter 9, we saw that a combination of (1) sympa-

Effect of Nervous Excitation to Increase Heart Pumping.

ulation and (2) hypertrophy of the heart muscle.

a better pump than normal. They are (1) nervous stim-

Factors That Can Cause Hypereffective Heart

that are pumping better than normal. The low-

mally. The uppermost curves are for

4 are several other cardiac

Shown in Figure 20

tion, can pump an amount of venous return up to

human heart, functioning without any special stimula-

output of about 5 L/min. This means that the normal

curve is about 13 L/min, 2.5 times the normal cardiac

which was discussed in Chapter 9. Note

function curve,

cardiac

level of right atrial pressure. This is one type of

, showing the cardiac output per minute at each

normal cardiac output

Figure 20–4 demonstrates the

curve

that the plateau level of this normal cardiac output

about 2.5 times the normal venous return before the
heart becomes a limiting factor in the control of
cardiac output.

–

output curves for hearts that are not pumping nor-

hypereffective

hearts
ermost curves are for hypoeffective hearts that are
pumping at levels below normal.

Only two types of factors usually can make the heart

thetic stimulation and (2) parasympathetic inhibition
does two things to increase the pumping effectiveness

—

100

120

140

160

Arterial pressure or cardiac output

(percentage of normal)

100

150

200

Total peripheral resistance

(percentage of normal)

output

Beriberi

AV shunts

Hyperthyroidism

Anemia

Normal

Pulmonary disease

Paget’s disease

Removal of both arms and legs

Hypothyroidism

dia

AC: Arterial Pressure and Hypertension. Philadelphia: WB

peripheral resistance and cardiac output. (Redrawn from Guyton

cardiac output, showing a reciprocal relationship between total

Chronic effect of different levels of total peripheral resistance on

Figure 20–3

Saunders Co, 1980.)

Cardiac output (L

/min)

–

Right atrial pressure (mm Hg)

Normal

Hypereffective

Hypoeffective

Coleman TB: Circulatory Physiology: Cardiac Output and Its

and hypereffective hearts. (Redrawn from Guyton AC, Jones CE,

Cardiac output curves for the normal heart and for hypoeffective

Figure 20–4

Regulation. 2nd ed. Philadelphia: WB Saunders Co, 1973.)

In summary, when local tissue vessels dilate and

ow through the active muscles.

above normal, which in turn forces still more blood

and increased contractility of the heart. All these

causing large vein constriction, increased heart rate,

centers of the brain to excite circulatory activity,

nervous system immediately compensates. The same

decrease the arterial pressure also. However, the

the total peripheral resistance, which normally would

muscle contraction. Obviously, this greatly decreases

During exercise, intense increase in

Effect of the Nervous System to

Chapter 18, is essential to achieve high cardiac outputs

exes, by mechanisms explained in

Thus, maintenance of a normal arterial pressure by

fall in arterial pressure to about one half normal, and

could function, and vasodilation of the vessels with

system had been blocked, none of the normal circula-

However, after autonomic control of the nervous

pressure from falling, dilating all the peripheral blood

the drug dinitrophenol, which increased the metabo-

nomic nervous system. The solid curves demonstrate

Figure 20

Venous Return and Cardiac Output Increase

Maintaining the Arterial Pressure When the

Importance of the Nervous System in

Nervous System in Controlling

What Is the Role of the

heart must pump, such as in hypertension

Valvular heart disease

Coronary artery blockage, causing a

blood causes hypoeffectivity. Some of the factors that

Factors That Cause a Hypoeffective Heart

s running time.

times normal; this increased level

40 L/min, about 2

and hypertrophy, as occurs in marathon runners, the

When one combines nervous excitation of the heart

the cardiac output curve, sometimes 60 to 100 per cent,

by 50 to 75 per cent. This increases the plateau level of

muscles to hypertrophy. For instance, it is common for

excess load that it damages the heart, causes the heart

A long-term increased workload, but not so much

Increased Pumping Effectiveness Caused by Heart Hypertrophy.

level of the uppermost curve in Figure 20

plateau of the normal curve, as shown by the 25-liter

strength. Combining these two effects, maximal

Cardiac Output, Venous Return, and Their Regulation

Chapter 20

235

72 beats/min up to 180 to 200 beats/min—and (2) it
increases the strength of heart contraction (which is
called increased “contractility”) to twice its normal

nervous excitation of the heart can raise the plateau
level of the cardiac output curve to almost twice the

–4.

muscle to increase in mass and contractile strength in
the same way that heavy exercise causes skeletal

the hearts of marathon runners to be increased in mass

and therefore allows the heart to pump much greater
than usual amounts of cardiac output.

total effect can allow the heart to pump as much 30 to

of pumping is one of the most important factors in
determining the runner’

Any factor that decreases the heart’s ability to pump

can do this are the following:

“heart

attack”

Inhibition of nervous excitation of the heart
Pathological factors that cause abnormal heart

rhythm or rate of heartbeat

Increased arterial pressure against which the

Congenital heart disease
Myocarditis
Cardiac hypoxia

Cardiac Output?

–5 shows an important difference in cardiac

output control with and without a functioning auto-

the effect in the normal dog of intense dilation of
the peripheral blood vessels caused by administering

lism of virtually all tissues of the body about fourfold.
Note that with nervous control to keep the arterial

vessels caused almost no change in arterial pressure
but increased the cardiac output almost fourfold.

tory reflexes for maintaining the arterial pressure

dinitrophenol (dashed curves) then caused a profound

the cardiac output rose only 1.6-fold instead of 4-fold.

the nervous refl

when the peripheral tissues dilate their vessels to
increase the venous return.

Increase the Arterial Pressure

During Exercise.

metabolism in active skeletal muscles acts directly on
the muscle arterioles to relax them and to allow ade-
quate oxygen and other nutrients needed to sustain

brain activity that sends motor signals to the muscles
sends simultaneous signals into the autonomic nervous

changes acting together increase the arterial pressure

thereby increase venous return and cardiac output

/min)

Cardiac output

Arterial pressure

(mm Hg)

100

With pressure control

Dinitrophenol

Without pressure control

Minutes

very little. (Drawn from experiments by Dr. M. Banet.)

sure control, the arterial pressure falls and the cardiac output rises

increases cardiac output greatly; without pres-

dinitrophenol

output control. Note that with pressure control, the metabolic stim-

maintenance of the arterial pressure as a prerequisite for cardiac

Experiment in a dog to demonstrate the importance of nervous

Figure 20–5

ulant

these is reduced viscosity of the blood, resulting

decrease the total peripheral resistance. One of

In anemia, two peripheral effects greatly

consequently, the venous return and cardiac output

Therefore, the total peripheral resistance decreases

vasodilator products are released from the tissues.

greatly increased. Oxygen usage increases, and

In hyperthyroidism, the

likewise, increases the venous return and cardiac

from the artery into the vein. This, too, greatly

vein, tremendous amounts of blood

stula (also called an AV

Earlier, we pointed

Arteriovenous fistula (shunt).

to as little as one-half normal. Consequently, the

of the tissues to use some cellular nutrients, and the

diet. Lack of this vitamin causes diminished ability

This disease is caused by insuf

sequently. For the present, let us look at some of the

excitation of the heart itself, which we will explain sub-

eral resistance.

they all result from chronically reduced total periph-

The left side of Figure 20

by Reduced Total Peripheral

important of these are shown in Figure 20

either high or low cardiac outputs. Some of the more

However, multiple clinical abnormalities can cause

surprisingly constant from one person to another.

In healthy human beings, the cardiac outputs are

Cardiac Outputs

even above normal, which serves to increase the

exercise, the nervous system goes even further, pro-

from falling to disastrously low levels. In fact, during

above normal, the nervous system plays an exceed-

236

Unit IV

The Circulation

ingly important role in preventing the arterial pressure

viding additional signals to raise the arterial pressure

cardiac output an extra 30 to 100 per cent.

Pathologically High and
Pathologically Low

–6.

High Cardiac Output Caused

Resistance

–6 identifies conditions that

commonly cause cardiac outputs higher than normal.
One of the distinguishing features of these conditions is
that

None of them result from excessive

conditions that can decrease the peripheral resistance

and at the same time increase the cardiac output to
above normal.
1. Beriberi.

ficient

quantity of the vitamin thiamine (vitamin B

) in the

local tissue blood flow mechanisms in turn cause
marked compensatory peripheral vasodilation.
Sometimes the total peripheral resistance decreases

long-term levels of venous return and cardiac
output also often increase to twice normal.

out that whenever a fi
shunt) occurs between a major artery and a major

flow directly

decreases the total peripheral resistance and,

output.

3. Hyperthyroidism.

metabolism of most tissues of the body becomes

markedly because of the local tissue blood
flow control reactions throughout the body;

often increase to 40 to 80 per cent above normal.

4. Anemia.

from the decreased concentration of red blood

/min/

Average 45-year-old adult

raumatic shock (4)

shunts (33)

Beriberi (5)

Hyperthyroidism (29)

Anemia (75)

Anxiety (21)

Pulmonary disease (29)

Pregnancy (46)

Paget

’s disease (9)

Control (young adults) (308)

Hypertension (47)

Mild valve disease (31)

Myocardial infarction (22)

Mild shock (4)

Severe valve disease (29)

Cardiac shock (7)

Control (young adults)

200

175

150

125

100

Cardiac output

(per cent of control)

Cardiac index

)

(Redrawn from Guyton AC, Jones CE, Coleman TB: Circulatory Physiology: Cardiac Output and Its Regulation. 2nd ed. Philadelphia:

Cardiac output in different pathological conditions. The numbers in parentheses indicate number of patients studied in each con

Figure 20–6

dition.

WB Saunders Co, 1973.)

50 mm Hg during strenuous breathing.

2 mm Hg during

, which are about

Cyclical changes of intrapleural pressure during

4 mm Hg, which shifts

2 mm Hg requires a 6 mm Hg increase in right

of the heart. Likewise, an increase in intrapleural pres-

with blood requires an extra 2 mm Hg right atrial pres-

This shift occurs because to

2 mm Hg, shifts the entire

intrapleural pressure, to

4 mm Hg. Note in the

nal cardiac pressure on the cardiac output curve. The

Figure 20

Curves.

the heart, as explained in the next section.

4. However, an additional set of

shown in Figure 20

venous return, and right atrial pressure at the same time.

Then one can put these

venous return curves.

ow of blood from the veins into the heart, as repre-

, and (2) the peripheral factors that affect

cardiac

pumping ability of the heart, as represented by

concerned with cardiac output regulation: (1) the

To perform the more quantitative analysis, it is nec-

sections.

cardiac failure, and circulatory shock, a more complex

stressful situations, such as the extremes of exercise,

cardiac output in most simple conditions. However, to

of Cardiac Output Regulation

A More Quantitative Analysis

within a few minutes to a few hours. Circulatory shock

This condition can be lethal

circulatory shock.

for adequate nutrition of the tissues, the person is said

whether it be a peripheral factor or a cardiac factor, if

ow needs of the muscles, resulting in

turn, decreases the total oxygen consumption and

reduction in the size of the skeletal muscles. This, in

periods of physical inactivity, there is usually a

With normal aging or with prolonged

muscle mass.

Consequently, the cardiac output falls markedly.

obstructed, so that the blood in the peripheral

On rare occasions,

Obstruction of the large veins.

result, the blood

accid peripheral blood vessels. As a

veins, to dilate markedly. This decreases the

the peripheral capacitative vessels, especially the

sympathetic nervous system activity, which causes

system suddenly becomes inactive. For instance,

peripheral veins become acutely vasodilated. This

On some occasions, the

output: Loss of blood decreases the

volume, resulting most often from hemorrhage.

By far, the most

Decreased blood volume.

cardiac output. Some of these factors are the following:

Factors—Decreased Venous Return.

cussed fully in Chapter 22 in relation to cardiac failure.

This is dis-

cardiac shock.

ciency, the condition is called

When the cardiac output falls so low that the tissues

6, demonstrating the low cardiac outputs that

Figure 20

The effects of several of these are shown on the right in

cardiac metabolic derangements.

, and (5)

cardiac

, (4)

myocarditis

, (3)

, (2)

blockage and consequent myocardial infarction

ow to the tissues. Some

of the cause, its limited level of pumping may fall below

ever the heart becomes severely damaged, regardless

When-

low.

fall into two categories: (1) those abnormalities that

cause abnormally low cardiac output. These conditions

Figure 20

consequence, the cardiac output increases greatly.

the tissues, which causes local vasodilation. As a

cells. The other is diminished delivery of oxygen to

Cardiac Output, Venous Return, and Their Regulation

Chapter 20

237

Any other factor that decreases the total peripheral

resistance chronically also increases the cardiac output.

Low Cardiac Output

–6 shows at the far right several conditions that

cause the pumping effectiveness of the heart to fall too
low and (2) those that cause venous return to fall too

Decreased Cardiac Output Caused by Cardiac Factors.

that needed for adequate blood fl
examples of this include (1) severe coronary blood vessel

severe valvular heart disease
tamponade

–

result.

throughout the body begin to suffer nutritional defi-

Decrease in Cardiac Output Caused by Non-cardiac Peripheral

Anything that inter-

feres with venous return also can lead to decreased

common non-cardiac peripheral factor that leads
to decreased cardiac output is decreased blood

It is clear why this condition decreases the cardiac

filling of the

vascular system to such a low level that there is not
enough blood in the peripheral vessels to create
peripheral vascular pressures high enough to push
the blood back to the heart.

2. Acute venous dilation.

results most often when the sympathetic nervous

fainting often results from sudden loss of

filling

pressure of the vascular system because the blood
volume can no longer create adequate pressure
in the now fl

“pools” in the vessels and does not

return to the heart.

the large veins leading into the heart become

vessels cannot flow back into the heart.

4. Decreased tissue mass, especially decreased skeletal

blood fl
decreases in skeletal muscle blood flow and cardiac
output.

Regardless of the cause of low cardiac output,

ever the cardiac output falls below that level required

to suffer

is such an important clinical problem that it is discussed
in detail in Chapter 24.

Our discussion of cardiac output regulation thus far is
adequate for understanding the factors that control

understand cardiac output regulation in especially

quantitative analysis is presented in the following

essary to distinguish separately the two primary factors

output curves
fl
sented by
curves together in a quantitative way to show how they
interact with each other to determine cardiac output,

Cardiac Output Curves Used in the
Quantitative Analysis

Some of the cardiac output curves used to depict quan-
titative heart pumping effectiveness have already been

–

curves is required to show the effect on cardiac output
caused by changing external pressures on the outside of

Effect of External Pressure Outside the Heart on Cardiac Output

–7 shows the effect of changes in exter-

normal external pressure is equal to the normal
intrapleural pressure (the pressure in the chest cavity),
which is

figure that a rise in

cardiac output curve to the right by the same amount.

fill the cardiac chambers

sure to overcome the increased pressure on the outside

sure to

atrial pressure from the normal

the entire cardiac output curve 6 mm Hg to the right.

Some of the factors that can alter the intrapleural

pressure and thereby shift the cardiac output curve are
the following:
1.

respiration

normal breathing but can be as much as
±

and causing venous stasis, pumping by the heart also

bag, so that any increase in back pressure causes blood

7 mm Hg. Such a slight rise in

nervous circulatory reflexes are prevented from acting

pressure to rise, the backward force of the rising atrial

curve. This curve shows that when heart pumping capa-

9 is the

The curve in Figure 20

levels of right atrial pressure.

that is, the venous

pumping of blood by the heart to right atrial pressure,

Normal Venous Return Curve

sections.

venous return curve,

These factors can all be expressed quantitatively

Resistance to blood flow

2. Degree of

, which exerts a backward force

heart from the systemic circulation. They are as follows:

different circulatory states. In these studies, one

venous pressure in the right atrium, are altered to

such blood volume, vascular resistances, and central

cial oxygenator system. Then, different factors,

circulation, we

can be achieved. To analyze the function of the systemic

There remains the entire systemic circulation that must

Venous Return Curves

heart to pump blood by a single cardiac output curve.

as a pump, one can express the momentary ability of the

a pump. Thus, by knowing what is happening to the

Figure 20

Combinations of Different Patterns of Cardiac Output Curves.

right. Note in Figure 20

, which means accumulation of

Cardiac tamponade

cardiac output curve to the right 4 mm Hg.

intrapleural pressure to 0 mm Hg and shifts the

, which increases the

, which shifts the curve to

Positive pressure breathing

, which shifts

238

Unit IV

The Circulation

2. Breathing against a negative pressure

the curve to a more negative right atrial pressure
(to the left).

the right.

4. Opening the thoracic cage

a large quantity of fluid in the pericardial cavity
around the heart with resultant increase in external
cardiac pressure and shifting of the curve to the

–7 that cardiac tamponade

shifts the upper parts of the curves farther to the
right than the lower parts because the external
“tamponade” pressure rises to higher values as the
chambers of the heart fill to increased volumes
during high cardiac output.

–8 shows that the final cardiac output curve can

change as a result of simultaneous changes in (a) exter-
nal cardiac pressure and (b) effectiveness of the heart as

external pressure as well as to the capability of the heart

be considered before total analysis of cardiac regulation

first remove the heart and lungs from the

circulation of an animal and replace them with a pump
and artifi

determine how the systemic circulation operates in

finds

three principal factors that affect venous return to the

1. Right atrial pressure

on the veins to impede flow of blood from the
veins into the right atrium.

filling of the systemic circulation

(measured by the mean systemic filling pressure),
which forces the systemic blood toward the heart
(this is the pressure measured everywhere in the
systemic circulation when all flow of blood is
stopped—we discuss this in detail later).

between the peripheral

vessels and the right atrium.

by the

as we explain in the next

In the same way that the cardiac output curve relates

the venous return curve relates venous return also to
right atrial pressure—

flow of blood

into the heart from the systemic circulation at different

–

normal venous return

bility becomes diminished and causes the right atrial

pressure on the veins of the systemic circulation
decreases venous return of blood to the heart. If all

venous return decreases to zero when the right atrial
pressure rises to about

right atrial pressure causes a drastic decrease in venous
return because the systemic circulation is a distensible

to dam up in this bag instead of returning to the heart.

At the same time that the right atrial pressure is rising

+12

Cardiac output (L

/min)

–4

Right atrial pressure (mm Hg)

Car

diac

tam

pona

–

)

–5

–

Cardiac Output and Its Regulation. 2nd ed. Philadelphia: WB

Guyton AC, Jones CE, Coleman TB: Circulatory Physiology:

and at different degrees of cardiac tamponade. (Redrawn from

Cardiac output curves at different levels of intrapleural pressure

Figure 20–7

Saunders Co, 1973.)

Hypoeffective

Hypereffective

+12

Cardiac output (L

/min)

–4

Right atrial pressure (mm Hg)

Normal

–increased

intrapleural pressure

–reduced

intrapleural pressure

Jones CE, Coleman TB: Circulatory Physiology: Cardiac Output

effectiveness of the heart as a pump. (Redrawn from Guyton AC,

showing the effect of alterations in both extracardiac pressure and

Combinations of two major patterns of cardiac output curves

Figure 20–8

and Its Regulation. 2nd ed. Philadelphia: WB Saunders Co, 1973.)

about 17 mm Hg.

pressure from 7 mm Hg to about 2.5 times that value, or

increased. At normal blood volume, maximal sympa-

blood volume, the mean circulatory

capacity of the system decreases, so that at each level of

and even the chambers of the heart. Therefore, the

lling pressure. Strong sympa-

10 show the effects, respectively,

in Figure 20

The

Mean Circulatory Filling Pressure.

Effect of Sympathetic Nervous Stimulation of the Circulation on

lling pressure increases almost linearly.

of 7 mm Hg. Similarly, at still higher volumes, the mean

of 5000 milliliters, the

of the circulation, but at a volume

blood volume of about 4000 milliliters, the mean circu-

lling pressure. Note that at a

in Figure 20

ture. The

The greater the volume of blood in the circulation, the

Effect of Blood Volume on Mean Circulatory Filling Pressure.

mean circulatory filling pressure.

become equal. This equilibrated pressure level is called

ow, the pressures everywhere in the circulation

the circulation ceases a few seconds later.Without blood

stopped in any other way,

When heart pumping is stopped by shocking the heart

Pressure, and Their Effect on Venous Return

Mean Circulatory Filling Pressure and Mean Systemic Filling

0 mm Hg.

veins. Consequently, even very negative pressures in the

veins together where they enter the chest, which pre-

entering the chest. Neg-

50 mm Hg, or even further.This plateau

20 mm Hg,

return will have reached a plateau. It remains at this

2 mm Hg, the venous

return almost ceases. And by the time the right atrial

that is, below

below

When the

Pressures—Caused by Collapse of the Large Veins.

Plateau in the Venous Return Curve at Negative Atrial

nition, is

ceases at a pressure of 7 mm Hg, which, by de

Cardiac Output, Venous Return, and Their Regulation

Chapter 20

239

approaches zero because of decreasing venous return.
Both the arterial and the venous pressures come to
equilibrium when all flow in the systemic circulation

the mean systemic filling pressure (Psf).

right atrial pressure falls

zero—

atmospheric pressure—further increase in venous

pressure has fallen to about

plateau level even though the right atrial pressure falls
to

is caused by collapse of the veins
ative pressure in the right atrium sucks the walls of the

vents any additional flow of blood from the peripheral

right atrium cannot increase venous return significantly
above that which exists at a normal atrial pressure of

with electricity to cause ventricular fibrillation or is

flow of blood everywhere in

the

greater is the mean circulatory filling pressure because
extra blood volume stretches the walls of the vascula-

red curve

–10 shows the approxi-

mate normal effect of different levels of blood volume
on the mean circulatory fi

latory filling pressure is close to zero because this is the
“unstressed volume”

filling pressure is the normal value

circulatory fi

green curve and blue

curve

–

of high and low levels of sympathetic nervous activity
on the mean circulatory fi
thetic stimulation constricts all the systemic blood
vessels as well as the larger pulmonary blood vessels

filling pressure is

thetic stimulation increases the mean circulatory filling

Venous return (L

/min)

–8

–

Transitional zone

Plateau

Down slo

Mean

systemic

filling

pressure

Right atrial pressure (mm Hg)

mean systemic filling pressure.

atrial pressure rises to equal the

becomes zero when the right

Note also that venous return

below atmospheric pressure.

when the right atrial pressure falls

venous return curve

Normal

Figure 20–9

. The

plateau is caused by collapse of
the large veins entering the chest

1000 2000 3000 4000 5000 6000 7000

–

Volume (ml)

Mean circulatory filling pressure (mm Hg)

Strong sympathetic
stimulation

Normal circulatory
system

Complete sympathetic
inhibition

Normal volume

culatory system). These curves also show the effects of strong

(i.e., “volume-pressure curves” for the entire cir-

filling pressure

mean circulatory

Effect of changes in total blood volume on the

Figure 20–10

sympathetic stimulation and complete sympathetic inhibition.

ow.

7 mm Hg, right atrial pressure equals 0 mm Hg, and

equals 5 L/min, mean systemic

adult, the values for these are as follows: venous return

is resistance to venous return. In the healthy human

lling pressure, PRA is right atrial pressure, and RVR

in which VR is venous return, Psf is mean systemic

Venous return can be calculated by the following

artery resistance.

ance, and about one third by the arteriolar and small

come much of the increased resistance. Mathematically,

the veins. Therefore, even slight accumulation of blood

resistances increase, blood accumulates in the arteries,

drastically. Conversely, when arteriolar and small artery

ance, and blood

are highly distensible. Therefore, this rise in venous

to be dammed up, mainly in the veins themselves. But

when the resistance in the veins increases, blood begins

ing the resistance to venous return? The answer is that

Why is venous resistance so important in determin-

occurs in the veins, although some occurs in the arteri-

ow of blood. It is called the

periphery toward the heart, there is also resistance to

Resistance to Venous Return

. Therefore, the difference between these

11. That is,

venous return curves in Figure 20

proportionately, as one can see by studying any of the

lling pressure, the

back to the right atrium. However, when the right atrial

vessels and the right atrium. Consequently, there can no

lling pressure, there is no

When the right atrial pressure rises

Is No Venous Return.

“Pressure Gradient for Venous Return”—When This Is Zero, There

lling, the more dif

The less the

lled, the easier it is for blood to

To express this another way, the greater the system is

downward

lling pressure,

Conversely, the lower the mean systemic

upward

decreased to 3.5 mm Hg. These curves demonstrate that

14 mm Hg, and for the lowermost curve, has been

gure,

7 mm Hg. Then, for the uppermost curve in the

lling pressure (Psf). Note in Figure

Figure 20

Effect on the Venous Return Curve of Changes in Mean Systemic

one tenth as much blood volume.

is almost always nearly

however

impossible to measure in the living animal, is the impor-

lation. The mean systemic pressure, although almost

by clamping the large blood vessels at the heart, so that

pressure. It is the pressure measured everywhere

Psf, is slightly different from the mean circulatory

The

tory Filling Pressure.

pressure.

steep the curves are. This means that even slight changes

10, note speci

Hg. Before leaving Figure 20

heart, decreasing the mean circulatory

Conversely, complete inhibition of the sympathetic

240

Unit IV

The Circulation

nervous system relaxes both the blood vessels and the

filling pressure

from the normal value of 7 mm Hg down to about 4 mm

–

fically how

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

Mean Systemic Filling Pressure and Its Relation to Mean Circula-

mean systemic filling pressure,

filling

in the

systemic circulation after blood flow has been stopped

the pressures in the systemic circulation can be meas-
ured independently from those in the pulmonary circu-

tant pressure for determining venous return. The mean
systemic filling pressure,

equal to the mean circulatory filling pressure because the
pulmonary circulation has less than one eighth as much
capacitance as the systemic circulation and only about

Filling Pressure.

–11 shows the effects on the

venous return curve caused by increasing or decreasing
the mean systemic fi
20–11 that the normal mean systemic filling pressure is

the mean systemic filling pressure has been increased to

the greater the mean systemic filling pressure (which
also means the greater the “tightness” with which the
circulatory system is filled with blood) the more the
venous return curve shifts

and to the right.

the more the curve shifts

and to the left.

flow into the heart.

ficult it is for blood to

flow into the heart.

to equal the mean systemic fi
longer any pressure difference between the peripheral

longer be any blood flow from any peripheral vessels

pressure falls progressively lower than the mean sys-
temic fi

flow to the heart increases

–

the greater

the difference between the mean systemic filling pressure
and the right atrial pressure, the greater becomes the
venous return
two pressures is called the pressure gradient for venous
return.

In the same way that mean systemic filling pressure rep-
resents a pressure pushing venous blood from the

this venous fl

resistance to

venous return. Most of the resistance to venous return

oles and small arteries as well.

the venous pressure rises very little because the veins

pressure is not very effective in overcoming the resist-

flow into the right atrium decreases

which have a capacitance only 1/30 as great as that of

in the arteries raises the pressure greatly—30 times as
much as in the veins—and this high pressure does over-

it turns out that about two thirds of the so-called “resist-
ance to venous return” is determined by venous resist-

formula:

filling pressure equals

resistance to venous return equals 1.4 mm Hg per liter
of blood fl

Psf

PRA

RVR

+12

Venous return (L

/min)

–

Right atrial pressure (mm Hg)

Normal

Psf = 3.5

Psf = 7

Psf = 14

Cardiac Output and Its Regulation. 2nd ed. Philadelphia: WB

Guyton AC, Jones CE, Coleman TB: Circulatory Physiology:

of altering the Psf to either 3.5 or 14 mm Hg. (Redrawn from

systemic filling pressure (Psf) is 7 mm Hg, and showing the effect

Venous return curves showing the normal curve when the mean

Figure 20–11

Saunders Co, 1973.)

venous return curve of Figure 20

the curve upward. As a result of these two effects, the

reducing the resistance to venous return, which rotates

vessels, thus reducing their resistance and thereby

time, the increased blood volume distends the blood

shifts the venous return curve to the right. At the same

lling pressure (Psf) to increase to 16 mm Hg, which

diately on infusing the large quantity of extra blood, the

14. Imme-

analysis of this effect is shown in Figure 20

the cardiac output to about 2.5 to 3 times normal. An

Effect of Increased Blood Volume on Cardiac Output.

, giving a normal

point A, called the

cardiac output, and venous return are all depicted by

fore, in the normal circulation, the right atrial pressure,

for both the heart and the systemic circulation. There-

point A, at which the venous return equals the cardiac

There is only one point on the graph,

normal cardiac

Two curves in the

against each other, as shown in Figure 20

venous return curve; and (3)

this in the form of a cardiac output curve; (2) determine

right atrial pressure in the following way: (1) Determine

Therefore, one can predict the cardiac output and

circulation must operate together. This means that (1)

In the complete circulation, the heart and the systemic

Venous Return Curves

Simultaneous Cardiac Output and

Right Atrial Pressure, Using

Analysis of Cardiac Output and

both these factors can operate simultaneously.

and resistance to venous return, demonstrating that

Figure 20

Combinations of Venous Return Curve Patterns.

lling pressure.

regardless of how much the heart might fail, is equal to

highest level to which the right atrial pressure can rise

ow is still zero. Therefore,

is in the circulation; the

ow of blood, it makes no difference what the resistance

lling pressure, venous return

a slope.

rotates the curve downward

a slope. Conversely, an

rotates the curve upward

and, therefore,

return curve, showing that a

Figure 20

Curve.

Effect of Resistance to Venous Return on the Venous Return

Cardiac Output, Venous Return, and Their Regulation

Chapter 20

241

–12 demonstrates the effect of different

levels of resistance to venous return on the venous

decrease in this resistance

to one-half normal allows twice as much flow of blood

to twice as great

increase in resistance to twice

normal

to one-half as great

Note also that when the right atrial pressure rises to

equal the mean systemic fi
becomes zero at all levels of resistance to venous return
because when there is no pressure gradient to cause
fl

the

the mean systemic fi

–13

shows effects on the venous return curve caused by
simultaneous changes in mean systemic pressure (Psf)

the venous return from the systemic circulation must

equal the cardiac output from the heart and (2) the right
atrial pressure is the same for both the heart and the
systemic circulation.

the momentary pumping ability of the heart and depict

the momentary state of flow from the systemic circula-
tion into the heart and depict this in the form of a

“equate” these curves

–14.

figure depict the

output curve (red line) and the normal venous return
curve (blue line).

output and at which the right atrial pressure is the same

equilibrium point

value for cardiac output of 5 liters per minute and a
right atrial pressure of 0 mm Hg .

A sudden

increase in blood volume of about 20 per cent increases

–

increased filling of the system causes the mean systemic
fi

–14 is shifted to the

2 resistance

Venous return (L

/min)

–

Right atrial pressure (mm Hg)

Norm

al r

sista

nce

resistanc

Psf = 7

Physiology: Cardiac Output and Its Regulation. 2nd ed. Philadel-

(Redrawn from Guyton AC, Jones CE, Coleman TB: Circulatory

ance to venous return.” Psf, mean systemic filling pressure.

Venous return curves depicting the effect of altering the “resist-

Figure 20–12

phia: WB Saunders Co, 1973.)

Venous return (L

/min)

–4

+12

Right atrial pressure (mm Hg)

Normal resistance

resistance

1/2 resistance

1/3 resistance

Psf = 10

Psf = 7

Psf = 2.3

Psf = 10.5

Physiology: Cardiac Output and Its Regulation. 2nd ed. Philadel-

(Redrawn from Guyton AC, Jones CE, Coleman TB: Circulatory

filling pressure (Psf) and in “resistance to venous return.”

showing the effects of simultaneous changes in mean systemic

Combinations of the major patterns of venous return curves,

Figure 20–13

phia: WB Saunders Co, 1973.)

1. The two red curves crossing at point A show the

stula, that is, after

Figure 20

cardiac output falls from point A to point B, which is a

. The

inhibition caused by total spinal anesthesia, demon-

curves in Figure 20

signals through the autonomic ganglia. The lowermost

, that blocks transmission of nerve

or by using some drug, such as

The sym-

occur within seconds or minutes.

, until other compensatory effects

Thus, differ-

the right atrial pressure hardly changes.

heart by nearly 100 per cent. As a result, the cardiac

the zero venous return level).And the sympathetic stim-

pressure of 0 min Hg. Note in the

each other at point A, which represents a normal venous

venous return curves are depicted; these equate with

15, the

In Figure 20

(2) In the systemic circulation, it

temic circulation: (1) It

ally, over a period of 10 to 40 minutes, the cardiac output

the systemic circulation to constrict. Therefore, gradu-

. These

autoregulatory increase in the peripheral resistance,

. (3) The excess

reservoirs, such as the liver and spleen, to distend, thus

, especially causing the venous blood

returning the blood volume toward normal. (2) The

transude out of the capillaries into the tissues, thereby

ately begin to occur: (1) The increased cardiac output

The greatly increased cardiac output

Blood Volume.

Further Compensatory Effects Initiated in Response to Increased

8 mm Hg.

venous return increase 2.5 to 3 times, and that the right

curve at point B, showing that the cardiac output and

right. This new curve equates with the cardiac output

242

Unit IV

The Circulation

atrial pressure rises to about

caused by increased blood volume lasts for only a few
minutes because several compensatory effects immedi-

increases the capillary pressure so that fluid begins to

increased pressure in the veins causes the veins to
continue distending gradually by the mechanism called
stress-relaxation

reducing the mean systemic pressure
blood flow through the peripheral tissues causes

thus increasing the resistance to venous return
factors cause the mean systemic filling pressure to
return back toward normal and the resistance vessels of

returns almost to normal.

Effect of Sympathetic Stimulation on Cardiac Output.

Sympa-

thetic stimulation affects both the heart and the sys-

makes the heart a stronger pump.

increases the mean

systemic filling pressure because of contraction of
the peripheral vessels—especially the veins—and it
increases the resistance to venous return.

–

normal cardiac output and

return and cardiac output of 5 L/min and a right atrial

figure that maximal

sympathetic stimulation (green curves) increases the
mean systemic filling pressure to 17 mm Hg (depicted
by the point at which the venous return curve reaches

ulation also increases pumping effectiveness of the

output rises from the normal value at equilibrium point
A to about double normal at equilibrium point D—and
yet
ent degrees of sympathetic stimulation can increase the
cardiac output progressively to about twice normal for
short periods of time

Effect of Sympathetic Inhibition on Cardiac Output.

pathetic nervous system can be blocked by inducing
total spinal anesthesia
hexamethonium

–15 show the effect of sympathetic

strating that (1) the mean systemic filling pressure falls
to about 4 mm Hg and (2) the effectiveness of the heart
as a pump decreases to about 80 per cent of normal

decrease to about 60 per cent of normal.

Effect of Opening a Large Arteriovenous Fistula.

–16

shows various stages of circulatory changes that occur
after opening a large arteriovenous fi
making an opening directly between a large artery and
a large vein.

normal condition.

Psf = 7

Psf = 16

+12

+16

Cardiac output and venous return (L

/min)

–

Right atrial pressure (mm Hg)

systemic filling pressure.

and right atrial pressure shift from point A to point B. Psf, mean

curve to become the dashed curve; as a result, the cardiac output

equal to 20 per cent of the blood volume causes the venous return

curves are normal. Transfusion of blood

venous return

(red line)

and right atrial pressure when the cardiac output

The two solid curves demonstrate an analysis of cardiac output

Figure 20–14

and

(blue line)

+12

+16

Cardiac output and venous return (L

/min)

–

Right atrial pressure (mm Hg)

Maximal sympathetic
stimulation
Moderate sympathetic
stimulation

Spinal anesthesia

Normal

Jones CE, Coleman TB: Circulatory Physiology: Cardiac Output

by total spinal anesthesia (point B). (Redrawn from Guyton AC,

thetic stimulation (from point A to point C), (2) maximal sympa-

Analysis of the effect on cardiac output of (1) moderate sympa-

Figure 20–15

thetic stimulation (point D), and (3) sympathetic inhibition caused

and Its Regulation. 2nd ed. Philadelphia: WB Saunders Co, 1973.)

return to zero.

systole reverses for a fraction of a second. This reverse

rapidly to a peak during systole, and then at the end of

owmeter. It demonstrates that the blood

17 shows a recording in a dog of blood

Figure 20

Pulsatile Output of the Heart as

oxygen Fick method

surgery. Two of the methods commonly used are the

In the human, except in rare instances, cardiac output

ter. An electromagnetic or ultrasonic

monary artery, or great veins entering the heart and

In animal experiments, one can cannulate the aorta, pul-

Cardiac Output

presented, and in Chapter 22, analyses of cardiac output

In Chapter 21,

pressure of about 6 mm Hg.

still further. Therefore, point D shows a cardiac

slightly, raising the level of the cardiac output curve

Also, the prolonged increased workload on the

12 mm Hg, shifting the

kidney output of urine. The mean systemic

By this time, the blood volume has increased

4. Point D shows the effect after several more weeks.

pressure to about 4 mm Hg.

rises to almost 16 L/min, and the right atrial

excitation of the heart. The cardiac output now

right, and (2) further elevation of the cardiac

all veins and arteries) from 7 to 9 mm Hg, thus

two other effects: (1) an increase in the mean

exes have restored

3. Point C represents the effects about 1 minute later,

3 mm Hg

from 5 L/min up to 13 L/min

increase in cardiac output

depicted by point B, is an

the heart can pump more easily. The net result,

the cardiac output curve

circulation, and (2) a

arteries into the venous system, bypassing most

. The principal effects are (1) a sudden and

2. The curves crossing at point B show the circulatory

Cardiac Output, Venous Return, and Their Regulation

Chapter 20

243

condition immediately after opening the large
fistula
precipitous rotation of the venous return curve
upward caused by the large decrease in resistance to
venous return when blood is allowed to flow with
almost no impediment directly from the large

of the resistance elements of the peripheral

slight increase in the level of

because opening the fistula

decreases the peripheral resistance and allows
an acute fall in arterial pressure against which

and an increase in

right atrial pressure to about

after the sympathetic nerve refl
the arterial pressure almost to normal and caused

systemic filling pressure (because of constriction of

shifting the venous return curve 2 mm Hg to the

output curve because of sympathetic nervous

because the slight reduction in arterial pressure and
the sympathetic stimulation have both reduced

filling

pressure has now risen to

venous return curve another 3 mm Hg to the right.

heart has caused the heart muscle to hypertrophy

output now of almost 20 L/min and a right atrial

Other Analyses of Cardiac Output Regulation.

analysis of cardiac output regulation during exercise is

regulation at various stages of congestive heart failure
are shown.

Methods for Measuring

measure the cardiac output using any type of flowme-

flowmeter can also

be placed on the aorta or pulmonary artery to measure
cardiac output.

is measured by indirect methods that do not require

and the indicator dilution method.

Measured by an Electromagnetic or
Ultrasonic Flowmeter

–

flow

in the root of the aorta made using an electromagnetic
fl

flow rises

flow causes the aortic valve to close and the flow to

+12

Cardiac output and venous return (L

/min)

–

Right atrial pressure (mm Hg)

Physiology: Cardiac Output and Its Regulation. 2nd ed. Philadel-

(Redrawn from Guyton AC, Jones CE, Coleman TB: Circulatory

volume has increased and the heart has begun to hypertrophy.

reflexes have become active; and D, several weeks after the blood

opening the AV fistula; C, 1 minute or so after the sympathetic

equilibrium points, are A, normal conditions; B, immediately after

pressure in a human being after a large arteriovenous (AV) fistula

Analysis of successive changes in cardiac output and right atrial

Figure 20–16

is suddenly opened. The stages of the analysis, as shown by the

phia: WB Saunders Co, 1973.)

Seconds

Flow (L/min)

20
15
10

5
0

tromagnetic flowmeter.

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

Figure 20–17

meter.

oxygen from the respired air, using any type of oxygen

rate of oxygen absorption

artery in the body. The

the right ventricle or pulmonary artery. And

nally, into

clavian vein, down to the right atrium, and,

up the brachial vein of the forearm, through the sub-

mixed venous

cardiac output in the human being,

In applying this Fick procedure for measuring

a measure of the cardiac output. Thus, the cardiac

through the lungs each minute is 5 liters, which is also

oxygen. Therefore, the quantity of blood

the blood from the lungs each minute is 200 milliliters,

per liter of blood. From these data, one can calculate

liters per liter of blood, whereas that leaving the left

each minute. It also shows that the blood entering the

18. This

The Fick principle is explained by Figure 20

Measurement of Cardiac Output Using

244

Unit IV

The Circulation

the Oxygen Fick Principle

–

figure shows that 200 milliliters of oxygen are being
absorbed from the lungs into the pulmonary blood

right heart has an oxygen concentration of 160 milli-

heart has an oxygen concentration of 200 milliliters

that each liter of blood passing through the lungs
absorbs 40 milliliters of oxygen.

Because the total quantity of oxygen absorbed into

dividing 200 by 40 calculates a total of five 1-liter por-
tions of blood that must pass through the pulmonary
circulation each minute to absorb this amount of

flowing

output can be calculated by the following formula:

blood is usually obtained through a catheter inserted

systemic

arterial blood can then be obtained from any systemic

the lungs is measured by the rate of disappearance of

Arteriovenous O difference ml L of blood

O absorbed per minute by the lungs ml min

Cardiac output L min

(

)

(

)

(

)

19, this was done by measuring the area under the

of the curve. For instance, in the top example of Figure

been determined, one then calculates the mean con-

curve. In this way, the

zero point, as shown by the dashed portion of each

rise again. For the purpose of calculation, it is necessary

sequently, the dye concentration in the artery began to

and returned through the heart for a second time. Con-

reached zero, some of the dye had already circulated all

concentration fell rapidly, but before the concentration

to a maximum in about 6 to 7 seconds. After that, the

arterial tree until about 3 seconds after the injection, but

In the top recording, none of the dye passed into the

ligrams of Cardio-Green dye was injected at zero time.

19. In each of these instances, 5 mil-

shown in Figure 20

through one of the peripheral arteries, giving a curve as

nally, into the systemic arterial system. The con-

vessels of the lungs, through the left side of the heart

the right side of the heart, then through the blood

ably, into the right atrium. This passes rapidly through

a dye, is injected into a large systemic vein or, prefer-

, such as

To measure cardiac output by the so-called

Indicator Dilution Method for
Measuring Cardiac Output

“indicator

dilution method,” a small amount of indicator

and, fi
centration of the dye is recorded as the dye passes

–

then the arterial concentration of the dye rose rapidly

the way through some of the peripheral systemic vessels

to extrapolate the early down-slope of the curve to the

extrapolated time-concentration

curve of the dye in the systemic artery without recircu-
lation can be measured in its first portion and estimated
reasonably accurately in its latter portion.

Once the extrapolated time-concentration curve has

centration of dye in the arterial blood for the duration

20–

160 ml/L

right heart

200 ml/L
left heart

Oxygen used = 200 ml/min

LUNGS

Cardiac output =

5000 ml/min

Fick principle for determining cardiac output.

Figure 20–18

Dye concentration in artery (mg/dl)

0.1

0.2

0.3

0.4

0.5

Seconds

0.1

0.2

0.3

0.4

0.5

5 mg

injected

5 mg

injected

rial blood for the durations of the respective extrapolated curves.)

areas are the calculated average concentrations of dye in the arte-

arate cardiac outputs by the dilution method. (The rectangular

Figure 20–19

Extrapolated dye concentration curves used to calculate two sep-

and diastolic heart failure. Annu Rev Med. 55:373, 2004.

Gaasch WH, Zile MR: Left ventricular diastolic dysfunction

94:849, 2003.

atrial pressure determines venous return. J Appl Physiol

Brengelmann GL: A critical analysis of the view that right

19. To summarize, the cardiac output can be

Figure 20

10 L/min. We leave it to the reader to calculate the

be the same as a cardiac output of 2 L/12 sec, or

through the heart during the 12 seconds, which would

dye through the heart and lungs in 12 seconds, a total

experiment. For blood carrying only 0.25 milligram of

of this average value was 12 seconds. A total of 5 mil-

Cardiac Output, Venous Return, and Their Regulation

Chapter 20

245

entire initial and extrapolated curve and then averaging
the concentration of dye for the duration of the curve;
one can see from the shaded rectangle straddling the
curve in the upper figure that the average concentration
of dye was 0.25 mg/dl of blood and that the duration

ligrams of dye had been injected at the beginning of the

dye in each deciliter to carry the entire 5 milligrams of

of 20 1-deciliter portions of blood would have passed

cardiac output from the bottom extrapolated curve of

–

determined using the following formula:

References

Milligrams of dye injected 60

Cardiac output ml min

Average concentration of dye

in each milliliter of blood

for the duration of the curve

Duration of

the curve

in seconds

(

)

˜ ¥

nisms in the conscious state. N Engl J Med 293:970, 1975.

Vatner SF, Braunwald E: Cardiovascular control mecha-

Physiol 286:H2376, 2004.

work of circulatory equilibrium. Am J Physiol Heart Circ

Uemura K, Sugimachi M, Kawada T, et al: A novel frame-

9:706-718, 1953.

left ventricular function curves in the dog. Circulation

of the heart, studied by means of simultaneous right and

Sarnoff SJ, Berglund E: Ventricular function. 1. Starling

Physiol Rev 63:1281, 1983.

ex control of veins and vascular capacitance.

Rothe CF: Re

measurement. J Appl Physiol 74:499, 1993.

lling pressure: its meaning and

Rothe CF: Mean circulatory

415:206, 2002.

brane-spanning receptors and heart function. Nature

Rockman HA, Koch WJ, Lefkowitz RJ: Seven-transmem-

naling. Annu Rev Physiol 62:237, 2000.

Koch WJ, Lefkowitz RJ, Rockman HA: Functional conse-

factors on cardiac output. Am J Physiol 180:463-468, 1955.

Guyton AC, Lindsey AW, Kaufmann BN: Effect of mean cir-

Saunders Co, 1973.

Cardiac Output and Its Regulation. Philadelphia: WB

Guyton AC, Jones CE, Coleman TG: Circulatory Physiology:

regulation. Annu Rev Physiol 34:13, 1972.

Guyton AC, Coleman TG, Granger HJ: Circulation: overall

Rev 35:123, 1955.

venous return curves with cardiac response curves. Physiol

Guyton AC: Determination of cardiac output by equating

Wilkins, 1963, p 1099.

book of Physiology. Sec 2, Vol. 2. Baltimore, Williams &

Guyton AC: Venous return. In: Hamilton WF (ed): Hand-

culatory filling pressure and other peripheral circulatory

quences of altering myocardial adrenergic receptor sig-

’s law