CHAPTER 20

Cardiac Output, Venous Return,

UNIT IV
and Their Regulation

Cardiac output is the quantity of blood pumped into the Effect of Age on Cardiac Output. Figure 20-­1 shows
aorta each minute by the heart. This is also the quantity of the cardiac output, expressed as cardiac index, at differ-
blood that flows through the circulation. Because cardiac ent ages. The cardiac index rises rapidly to a level greater
output is the sum of the blood flow to all the tissues of the than 4 L/min/m2 at age 10 years and declines to about 2.4
body, it is one of the most important factors to consider in L/min/m2 at age 80 years. We explain later in this chapter
relation to function of the cardiovascular system. that the cardiac output is regulated throughout life almost
Venous return is equally important because it is the directly in proportion to overall metabolic activity. There-
quantity of blood flowing from the veins into the right fore, the declining cardiac index is indicative of declining
atrium each minute. The venous return and the cardiac activity and/or declining muscle mass with age.
output must equal each other except for a few heartbeats
when blood is temporarily stored in or removed from the CONTROL OF CARDIAC OUTPUT BY
heart and lungs. VENOUS RETURN—FRANK-­STARLING
MECHANISM OF THE HEART
NORMAL VALUES FOR CARDIAC Although heart function is obviously crucial in determin-
OUTPUT AT REST AND DURING ing cardiac output, the various factors of the peripheral
ACTIVITY circulation that affect flow of blood into the heart from
Cardiac output varies widely with the level of activity of the veins, called venous return, are normally the primary
the body. The following factors, among others, directly controllers of cardiac output.
affect cardiac output: (1) the basic level of body metabo- The main reason why peripheral factors are usually so
lism; (2) whether the person is exercising; (3) the person’s important in controlling cardiac output is that the heart
age; and (4) the size of the body. has a built-­in mechanism that normally allows it to pump
For young healthy men, resting cardiac output averages automatically the amount of blood that flows from the
about 5.6 L/min. For women, this value is about 4.9 L/min. veins into the right atrium. This mechanism, called the
When one considers the factor of age as well—because Frank-­Starling law of the heart, was discussed in Chapter
with increasing age, body activity and mass of some tis- 9. Basically, this law states that when increased quanti-
sues (e.g., skeletal muscle) diminish—the average cardiac ties of blood flow into the heart, the increased volume
output for the resting adult, in round numbers, is often of blood stretches the walls of the heart chambers. As a
stated to be about 5 L/min. However, cardiac output var- result of the stretch, the cardiac muscle contracts with
ies considerably among healthy men and women depend- increased force, and this action ejects the extra blood that
ing on muscle mass, adiposity, physical activity, and other has entered from the systemic circulation. Therefore, the
factors that influence metabolic rate and nutritional needs blood that flows into the heart is automatically pumped
of the tissues. without delay into the aorta and flows again through the
circulation.
Cardiac Index Another important factor, discussed in Chapters 10 and
18, is that stretching the heart causes an increased heart rate.
Experiments have shown that the cardiac output increases
approximately in proportion to the surface area of the body. Stretch of the sinus node in the wall of the right atrium has
Therefore, cardiac output is frequently stated in terms of a direct effect on the rhythmicity of the node to increase the
the cardiac index, which is the cardiac output per square heart rate as much as 10% to 15%. In addition, the stretched
meter of body surface area. The average person who weighs right atrium initiates a nervous reflex called the Bainbridge
70 kilograms has a body surface area of about 1.7 square reflex, passing first to the vasomotor center of the brain and
meters, which means that the normal average cardiac index then back to the heart by way of the sympathetic nerves and
for adults is about 3 L/min/m2 of body surface area. vagi, which also increases the heart rate.

245
UNIT IV The Circulation

Cardiac output = Total tissue blood flow

Cardiac index (L/min/m2) 4 4

3 3
Right heart Lungs Left heart

2 2 14%
Brain

4%
Heart
1 1 Venous Cardiac
return Splanchnic 27% output
(vena cava) circulation (aorta)

0 0 22%
Kidneys
(years) 0 10 20 30 40 50 60 70 80
Age 15%
Muscle
Figure 20-­1. Cardiac index for a person—cardiac output per square (inactive)
meter of surface area—at different ages. (Modified from Guyton AC,
Jones CE, Coleman TG: Circulatory Physiology: Cardiac Output and Its 18%
Skin, other
Regulation, 2nd ed. Philadelphia: WB Saunders, 1973.) tissues

Figure 20-­2. Cardiac output is equal to venous return and is the sum
Under most normal unstressed conditions, the cardiac of tissue and organ blood flows. Except when the heart is severely
output is controlled mainly by peripheral factors that weakened and unable to pump the venous return adequately, cardiac
determine venous return. However, as we discuss later output (total tissue blood flow) is determined mainly by the metabolic
in the chapter, if the returning blood does become more needs of the tissues and organs of the body.
than the heart can pump, then the heart becomes the lim-
iting factor that determines cardiac output. Cardiac output
35 and cardiac index

Oxygen consumption (L/min)

Cardiac Output Is the Sum of All Tissue Oxygen
Cardiac output (L/min)

30
Cardiac index (L/min/m2)

Blood Flows—Tissue Metabolism 15 consumption 4

25
Regulates Most Local Blood Flow
20 3
The venous return to the heart is the sum of all the local 10
15
blood flow through all the individual tissue segments of 2
the peripheral circulation (Figure 20-­2). Therefore, it fol- 5 10
1
lows that cardiac output regulation is normally the sum of 5
all the local blood flow regulations. 0 0 0
The mechanisms of local blood flow regulation were 0 400 800 1200 1600
discussed in Chapter 17. In most tissues, blood flow Work output during exercise (kg-m/min)
increases mainly in proportion to each tissue’s metab- Figure 20-­3. Effect of increasing levels of exercise to increase car-
olism. For example, local blood flow almost always diac output (red solid line) and oxygen consumption (blue dashed
increases when tissue oxygen consumption increases; this line). (Modified from Guyton AC, Jones CE, Coleman TG: Circulatory
effect is demonstrated in Figure 20-­3 for different lev- Physiology: Cardiac Output and Its Regulation, 2nd ed. Philadelphia:
WB Saunders, 1973.)
els of exercise. Note that at each increasing level of work
output during exercise, oxygen consumption and cardiac
output increase in parallel to each other. output control: Under many conditions, the long-­term
To summarize, cardiac output is usually determined cardiac output level varies reciprocally with changes in
by the sum of all the various factors throughout the body total peripheral vascular resistance as long as the arterial
that control local blood flow. All the local blood flows pressure is unchanged. Note in Figure 20-­4 that when
summate to form the venous return, and the heart auto- the total peripheral resistance is exactly normal (at the
matically pumps this returning blood back into the arter- 100% mark in the figure), the cardiac output is also nor-
ies to flow around the system again. mal. Then, when the total peripheral resistance increases
above normal, the cardiac output falls; conversely, when
Cardiac Output Varies Inversely With Total Peripheral the total peripheral resistance decreases, the cardiac out-
Resistance When Arterial Pressure Is Unchanged. Fig- put increases. One can easily understand this phenom-
ure 20-­3 is the same as Figure 19-­5. It is repeated here enon by reconsidering one of the forms of Ohm’s law, as
to illustrate an extremely important principle in cardiac expressed in Chapter 14:

246
 Chapter 20 Cardiac Output, Venous Return, and Their Regulation

25

Removal of both arms and legs

Beriberi

Hyperthyroidism
AV shunts

Pulmonary disease
Paget’s disease
20
200 Hypereffective
Arterial pressure or cardiac output

Cardiac output (L/min)

Hypothyroidism

UNIT IV
15

Ca
150 ia Normal

rd
c
(% of normal)

Normal
Anemia
100 10
out
put
Hypoeffective

50 5

0 0
40 60 80 100 120 140 160 −4 0 +4 +8
Total peripheral resistance Right atrial pressure (mm Hg)
(% of normal)
Figure 20-­5. Cardiac output curves for the normal heart and for
Figure 20-­4. Chronic effect of different levels of total peripheral hypoeffective and hypereffective hearts. (Modified from Guyton AC,
resistance on cardiac output, showing a reciprocal relationship be- Jones CE, Coleman TG: Circulatory Physiology: Cardiac Output and Its
tween total peripheral resistance and cardiac output. AV, Atrioven- Regulation, 2nd ed. Philadelphia: WB Saunders, 1973.)
tricular. (Modified from Guyton AC: Arterial Pressure and Hyperten-
sion. Philadelphia: WB Saunders, 1980.)
Nervous Excitation Can Increase Heart Pumping.
Arterial pressure In Chapter 9, we saw that a combination of sympathet-
Cardiac output =
Total peripheral resistance ic stimulation and parasympathetic inhibition does two
things to increase the pumping effectiveness of the heart:
Thus, any time the long-­term level of total peripheral (1) it greatly increases the heart rate—sometimes, in
resistance changes (but no other functions of the circula- young people, from the normal level of 72 beats/min up to
tion change), the cardiac output changes quantitatively in 180 to 200 beats/min—and (2) it increases the strength of
exactly the opposite direction. heart contraction (called increased contractility) to twice
its normal strength. Combining these two effects, maxi-
Limits for the Cardiac Output mal nervous excitation of the heart can raise the plateau
There are definite limits to the amount of blood that the level of the cardiac output curve to almost twice the pla-
heart can pump, which can be expressed quantitatively in teau of the normal curve, as shown by the 25-­L/min level
the form of cardiac output curves. of the uppermost curve in Figure 20-­5.
Figure 20-­5 demonstrates the normal cardiac output
curve, showing the cardiac output per minute at each level Heart Hypertrophy Can Increase Pumping Effectiveness.
of right atrial pressure. This is one type of cardiac func- A long-­term increased workload, but not so much excess
tion curve, which was discussed in Chapter 9. Note that load that it damages the heart, causes the heart muscle to
the plateau level of this normal cardiac output curve is increase in mass and contractile strength in the same way
about 13 L/min, 2.5 times the normal cardiac output of that heavy exercise causes skeletal muscles to hypertrophy.
about 5 L/min. This means that the normal human heart, For example, the hearts of marathon runners may be in-
functioning without any special stimulation, can pump a creased in mass by 50% to 75%. This factor increases the
venous return up to about 2.5 times the normal venous plateau level of the cardiac output curve, sometimes 60% to
return before the heart becomes a limiting factor in the 100%, and therefore allows the heart to pump much greater
control of cardiac output. than the usual amounts of cardiac output.
Shown in Figure 20-­5 are several other cardiac output When one combines nervous excitation of the heart and
curves for hearts that are not pumping normally. The upper- hypertrophy, as occurs in marathon runners, the total effect
most curves are for hypereffective hearts that are pumping can allow the heart to pump as much 30 to 40 L/min, about
better than normal. The lowermost curves are for hypoeffec- 2.5 times the level that can be achieved in the average person.
tive hearts that are pumping at levels below normal. This increased level of pumping is one of the most important
factors in determining the runner’s running time.
Factors That Cause a Hypereffective Heart
Two general types of factors that can make the heart a Factors That Cause a Hypoeffective Heart
stronger pump than normal are nervous stimulation and Any factor that decreases the heart’s ability to pump
hypertrophy of the heart muscle. blood causes hypoeffectivity. Some of the factors that

247
UNIT IV The Circulation

can decrease the heart’s ability to pump blood are the Chapter 18, is essential to achieve high cardiac outputs
following: when the peripheral tissues dilate their blood vessels to
• Increased arterial pressure against which the heart increase the venous return.
must pump, such as in severe hypertension
• Inhibition of nervous excitation of the heart Effect of Nervous System to Increase Arterial Pressure
• Pathological factors that cause abnormal heart During Exercise. During exercise, intense increases in
rhythm or rate of heartbeat metabolism in active skeletal muscles cause relaxation
• Coronary artery blockage, causing a heart attack of muscle arterioles to allow adequate oxygen and oth-
• Valvular heart disease er nutrients needed to sustain muscle contraction. This
• Congenital heart disease greatly decreases the total peripheral resistance, which
• Myocarditis, an inflammation of the heart muscle normally would decrease the arterial pressure as well.
• Cardiac hypoxia However, the nervous system immediately compensates.
The same brain activity that sends motor signals to the
muscles sends simultaneous signals into the autonomic
NERVOUS SYSTEM REGULATION OF
nervous centers of the brain to excite circulatory activity,
CARDIAC OUTPUT
causing large vein constriction, increased heart rate, and
Importance of Nervous System For Maintaining Ar- increased contractility of the heart. All these changes act-
terial Pressure When Peripheral Blood Vessels Are ing together increase the arterial pressure above normal,
Dilated and Venous Return and Cardiac Output In- which in turn forces still more blood flow through the ac-
crease. Figure 20-­6 shows an important difference in tive muscles.
cardiac output control with and without a functioning In summary, when local tissue blood vessels dilate and
autonomic nervous system. The solid curves demon- increase venous return and cardiac output above normal,
strate the effect in the normal dog of intense dilation of the nervous system plays a key role in preventing the arte-
the peripheral blood vessels caused by administering the rial pressure from falling to disastrously low levels. During
drug dinitrophenol, which increased the metabolism of exercise, the nervous system goes even further, providing
virtually all tissues of the body about fourfold. With nerv- additional signals to raise the arterial pressure above nor-
ous control mechanisms intact, dilating all the peripheral mal, which serves to increase the cardiac output an extra
blood vessels caused almost no change in arterial pressure 30% to 100%.
but increased the cardiac output almost fourfold. How-
ever, after autonomic control of the nervous system was Pathologically High or Low Cardiac Outputs
blocked, vasodilation of the blood vessels with dinitro-
Multiple clinical abnormalities can cause either high or low
phenol (dashed curves) then caused a profound fall in ar-
cardiac outputs. Some of the more important of these ab-
terial pressure to about one-­half normal, and the cardiac normal cardiac outputs are shown in Figure 20-­7.
output increased only 1.6-­fold instead of fourfold.
Thus, maintenance of a normal arterial pressure by High Cardiac Output Caused by Reduced Total
the nervous system reflexes, by mechanisms explained in Peripheral Resistance
The left side of Figure 20-­7 identifies conditions that cause
With nervous control abnormally high cardiac outputs. One of the distinguish-
Without nervous control ing features of these conditions is that they all result from
6
Dinitrophenol chronically reduced total peripheral resistance None of
Cardiac output

5 them result from excessive excitation of the heart itself,

(L/min)

4 which we will explain subsequently. Let us consider some

3 of the conditions that can decrease the peripheral resist-
2 ance and at the same time increase the cardiac output to
0 above normal.
1. Beriberi. This disease is caused by insufficient quantity
Arterial pressure

100 of the vitamin thiamine (vitamin B1) in the diet. Lack

(mm Hg)

75 of this vitamin causes diminished ability of the tis-

sues to use some cellular nutrients, and the local tissue
50
blood flow control mechanisms in turn cause marked
0 compensatory peripheral vasodilation. Sometimes the
0 10 20 30 total peripheral resistance decreases to as little as half-­
Minutes normal. Consequently, the long-­term levels of venous
Figure 20-­6. Experiment in a dog to demonstrate the importance return and cardiac output also may increase to twice the
of nervous maintenance of the arterial pressure as a prerequisite for normal value.
cardiac output control. Note that with pressure control, the meta- 2. Arteriovenous (AV) fistula (shunt). Earlier, we pointed out
bolic stimulant dinitrophenol increased cardiac output greatly; with- that whenever a fistula (also called an AV shunt) occurs
out pressure control, the arterial pressure fell, and the cardiac output between a major artery and major vein, large amounts
increased very little. (Drawn from experiments by Dr. M. Banet.)

248
 Chapter 20 Cardiac Output, Venous Return, and Their Regulation

of blood flow directly from the artery into the vein. This (4) cardiac tamponade; and (5) cardiac metabolic derange-
also greatly decreases the total peripheral resistance and, ments. The effects of several of these conditions are shown
likewise, increases the venous return and cardiac output. on the right in Figure 20-­7, demonstrating the low cardiac
3. 
Hyperthyroidism. In hyperthyroidism, the metabolism outputs that result.
of most tissues of the body becomes greatly increased. When the cardiac output falls so low that the tissues
Oxygen usage increases, and vasodilator products are throughout the body begin to suffer nutritional deficiency,

UNIT IV
released from the tissues. Therefore, total peripheral the condition is called cardiac shock. This condition is dis-
resistance decreases markedly because of local tissue cussed in Chapter 22 in relationship to cardiac failure.
blood flow control reactions throughout the body; con- Decreased Cardiac Output Caused by Noncardiac
sequently, venous return and cardiac output often in- Peripheral Factors—Decreased Venous Return. Anything
crease to 40% to 80% above normal. that interferes with venous return also can lead to decreased
4. 
Anemia. In anemia, two peripheral effects greatly de- cardiac output. Some of these factors are as follows:
crease total peripheral resistance. One of these effects 1. 
Decreased blood volume. The most common noncardiac
is reduced viscosity of the blood, resulting from the peripheral factor that leads to decreased cardiac output
decreased concentration of red blood cells. The other is decreased blood volume, often from hemorrhage.
effect is diminished delivery of oxygen to the tissues, Loss of blood may decrease the filling of the vascular
which causes local vasodilation. As a consequence, car- system to such a low level that there is not enough blood
diac output increases greatly. in the peripheral vessels to create peripheral vascular
Any other factor that decreases total peripheral resist- pressures high enough to push the blood back to the
ance chronically also increases cardiac output if arterial heart.
pressure does not decrease too much. 2. 
Acute venous dilation. Acute venous dilation results
most often when the sympathetic nervous system sud-
Low Cardiac Output
denly becomes inactive. For example, fainting often
Figure 20-­7 shows at the far right several conditions that results from sudden loss of sympathetic nervous sys-
cause abnormally low cardiac output. These conditions fall tem activity, which causes the peripheral capacitative
into two categories: (1) abnormalities that decrease pump- vessels, especially the veins, to dilate markedly. This
ing effectiveness of the heart; and (2) those that decrease dilation decreases the filling pressure of the vascular
venous return. system because the blood volume can no longer create
Decreased Cardiac Output Caused by Cardiac Factors. adequate pressure in the now flaccid peripheral blood
Whenever the heart becomes severely damaged, regardless vessels. As a result, the blood pools in the vessels and
of the cause, its limited level of pumping may fall below does not return to the heart as rapidly as normal.
that needed for adequate blood flow to the tissues. Some 3. 
Obstruction of the large veins. On rare occasions, the large
examples of this condition include the following: (1) severe veins leading into the heart become obstructed, and the
coronary blood vessel blockage and consequent myocardial blood in the peripheral vessels cannot flow back into the
infarction; (2) severe valvular heart disease; (3) myocarditis; heart. Consequently, the cardiac output falls markedly.

200 7

175 6

150
5

125
Cardiac output
(% of control)

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)

Paget’s disease (9)

2
Traumatic shock (4)

50
Hypertension (47)
Pregnancy (46)
AV shunts (33)

Cardiac shock (7)

Mild shock (4)
Anemia (75)

Anxiety (21)
Beriberi (5)

1
25

0 0
Figure 20-­7. Cardiac output in different pathological conditions. The numbers in parentheses indicate the number of patients studied in each
condition. AV, Atrioventricular. (Modified from Guyton AC, Jones CE, Coleman TG: Circulatory Physiology: Cardiac Output and Its Regulation,
2nd ed. Philadelphia: WB Saunders, 1973.)

249
UNIT IV The Circulation

4. Decreased tissue mass, especially decreased skeletal shifts the entire cardiac output curve to the right by the
muscle mass. With normal aging or with prolonged pe- same amount. This shift occurs because filling the car-
riods of physical inactivity, a reduction in the size of the diac chambers with blood requires an extra 2 mm Hg
skeletal muscles usually occurs. This reduction, in turn, of right atrial pressure to overcome the increased pres-
decreases the total oxygen consumption and blood flow
sure on the outside of the heart. Likewise, an increase in
needs of the muscles, resulting in decreases in skeletal
intrapleural pressure to +2 mm Hg requires a 6 m ­ m Hg
muscle blood flow and cardiac output.
5. Decreased metabolic rate of the tissues. If the tissue met- increase in right atrial pressure from the normal −4 mm
abolic rate is reduced, as occurs in skeletal muscle dur- Hg, which shifts the entire cardiac output curve 6 mm
ing prolonged bed rest, the oxygen consumption and Hg to the right.
nutrition needs of the tissues will also be lower, which Some factors that can alter the external pressure on the
decreases blood flow to the tissues, resulting in reduced heart and thereby shift the cardiac output curve are the
cardiac output. Other conditions, such as hypothyroid- following:
ism, may also reduce metabolic rate and therefore tissue 1. Cyclical changes of intrapleural pressure during res-
blood flow and cardiac output. piration, which are about ±2 mm Hg during normal
Regardless of the cause of low cardiac output, whether it breathing but can be as much as ±50 mm Hg during
is a peripheral factor or a cardiac factor, if the cardiac out-
strenuous breathing
put ever falls below the level required for adequate nutrition
2. Breathing against a negative pressure, which shifts
of the tissues, the person is said to experience circulatory
shock. This condition can be lethal within a few minutes to the curve to a more negative right atrial pressure (to
a few hours. Circulatory shock is such an important clinical the left).
problem that it is discussed in detail in Chapter 24. 3. Positive-­pressure breathing, which shifts the curve
to the right
4. Opening the thoracic cage, which increases the in-
trapleural pressure to 0 mm Hg and shifts the car-
CARDIAC OUTPUT CURVES USED IN
diac output curve to the right by 4 mm Hg
QUANTITATIVE ANALYSIS OF CARDIAC
5. Cardiac tamponade, which means accumulation
OUTPUT REGULATION
of a large quantity of fluid in the pericardial cavity
Our discussion of cardiac output regulation thus far around the heart with a resultant increase in exter-
is adequate for understanding the factors that control nal cardiac pressure and shifting of the curve to the
cardiac output in most simple conditions. However, to right
understand cardiac output regulation in especially stress- Note in Figure 20-­8 that cardiac tamponade shifts
ful situations, such as the extremes of exercise, cardiac the upper parts of the curves farther to the right than
failure, and circulatory shock, a more complex quantita- the lower parts because the external tamponade pressure
tive analysis is presented in the following sections. rises to higher values as the chambers of the heart fill to
To perform the more quantitative analysis, it is nec- increased volumes during high cardiac output.
essary to distinguish separately the two primary factors
concerned with cardiac output regulation: (1) the pump- Combinations of Different Patterns of Cardiac Output
ing ability of the heart, as represented by cardiac output Curves. Figure 20-­9 shows that the final cardiac output
curves; and (2) the peripheral factors that affect flow curve can change as a result of simultaneous changes
of blood from the veins into the heart, as represented in the following: (1) external cardiac pressure; and (2)
by venous return curves. Then we can put these curves effectiveness of the heart as a pump. For example, the
together in a quantitative way to show how they inter-
act with each other to determine cardiac output, venous
15
return, and right atrial pressure at the same time. Hg
m 4) g
Cardiac output (L/min)

Some of the cardiac output curves used to depict m

=– Hg
H

e
onad
mm
res .5

e
mm

quantitative heart pumping effectiveness have already amp

5

iac t
r
=–
su

Card
= +2
–2

10
been shown in Figure 20-­5. However, an additional set
sure

ure =
ural p

of curves is required to show the effect on cardiac output

ssur
al pres

press
aple

caused by changing external pressures on the outside of

l pre
pleur

5
l (intr

the heart, as explained in the next section.

ural

a
leur
Intra

aple
r ma

rap
Intr
No

Effect of External Pressure Outside the Heart on

Int

0
Cardiac Output Curves. Figure 20-­8 shows the effect
–4 0 +4 +8 +12
of changes in external cardiac pressure on the cardiac
Right atrial pressure (mm Hg)
output curve. The normal external pressure is equal to
Figure 20-­8. Cardiac output curves at different levels of intrapleural
the normal intrapleural pressure (the pressure in the pressure and different degrees of cardiac tamponade. (Modified from
chest cavity), which is about −4 mm Hg. Note in the fig- Guyton AC, Jones CE, Coleman TG: Circulatory Physiology: Cardiac
ure that a rise in intrapleural pressure, to −2 mm Hg, Output and Its Regulation, 2nd ed. Philadelphia: WB Saunders, 1973.)

250
 Chapter 20 Cardiac Output, Venous Return, and Their Regulation

Hypereffective + increased Transitional

Venous return (L/min)

intrapleural pressure Plateau zone
15 Mean
Normal 5 Do systemic
Cardiac output (L/min) wn
slo filling
pe pressure
10

UNIT IV
0
Hypoeffective + reduced –8 –4 0 +4 +8
5
intrapleural pressure Right atrial pressure (mm Hg)
Figure 20-­10. Normal venous return curve. The plateau is caused
by collapse of the large veins entering the chest when the right atrial
0 pressure falls below atmospheric pressure. Note also that venous re-
–4 0 +4 +8 +12
turn becomes zero when the right atrial pressure rises to equal the
Right atrial pressure (mm Hg) mean systemic filling pressure.
Figure 20-­9. Combinations of two major patterns of cardiac output
curves showing the effect of alterations in both extracardiac pressure
and effectiveness of the heart as a pump. (Modified from Guyton AC,
Normal Venous Return Curve
Jones CE, Coleman TG: Circulatory Physiology: Cardiac Output and Its In the same way that the cardiac output curve relates
Regulation, 2nd ed. Philadelphia: WB Saunders, 1973.) pumping of blood by the heart to right atrial pressure,
the venous return curve relates venous return also to right
combination of a hypereffective heart and increased in- atrial pressure—that is, the venous flow of blood into the
trapleural pressure would lead to an increased maximum heart from the systemic circulation at different levels of
level of cardiac output due to the increased pumping ca- right atrial pressure.
pability of the heart, but the cardiac output curve would The curve in Figure 20-­10 is the normal venous
be shifted to the right (to higher atrial pressures) because return curve. This curve shows that when heart pump-
of the increased intrapleural pressure. Thus, by knowing ing capability becomes diminished and causes the right
what is happening to the external pressure, and to the ca- atrial pressure to rise, the backward force of the rising
pability of the heart as a pump, one can express the mo- atrial pressure on the veins of the systemic circulation
mentary ability of the heart to pump blood by a single decreases venous return of blood to the heart. If all
cardiac output curve. nervous circulatory reflexes are prevented from acting,
venous return decreases to zero when the right atrial
pressure rises to about +7 mm Hg. Such a slight rise in
VENOUS RETURN CURVES
right atrial pressure causes a drastic decrease in venous
The entire systemic circulation must be considered before return because any increase in back pressure causes
complete analysis of cardiac regulation can be achieved. blood to dam up in the systemic circulation instead of
To analyze the function of the systemic circulation exper- returning to the heart.
imentally, the heart and lungs were removed from the At the same time that the right atrial pressure is ris-
circulation of an animal and replaced with a pump and ing and causing venous stasis, pumping by the heart also
artificial oxygenator system. Then, different factors, such approaches zero because of decreasing venous return.
as blood volume, vascular resistances, and central venous Both the arterial and venous pressures reach equilibrium
pressure in the right atrium, were altered to determine when all flow in the systemic circulation ceases at a pres-
how the systemic circulation operates in different circu- sure of 7 mm Hg, which, by definition, is the mean sys-
latory states. From these studies, one finds the following temic filling pressure.
three principal factors that affect venous return to the
heart from the systemic circulation: Plateau in Venous Return Curve at Negative Atrial
1. Right atrial pressure, which exerts a backward force Pressures Caused by Collapse of the Large Veins.
on the veins to impede flow of blood from the veins When the right atrial pressure falls below zero—that is,
into the right atrium. below atmospheric pressure—any further increase in ve-
2. Degree of filling of the systemic circulation (meas- nous return almost ceases, and by the time the right atrial
ured by the mean systemic filling pressure), which pressure has fallen to about −2 mm Hg, the venous return
forces the systemic blood toward the heart (this is reaches a plateau. It remains at this plateau level, even
the pressure measured everywhere in the systemic though the right atrial pressure falls to −20 mm Hg, −50
circulation when all flow of blood is stopped, dis- mm Hg or even further. This plateau is caused by collapse
cussed in detail later). of the veins entering the chest. Negative pressure in the
3. Resistance to blood flow between the peripheral ves- right atrium sucks the walls of the veins together where
sels and the right atrium. they enter the chest, which prevents any additional flow of
These factors can all be expressed quantitatively by the blood from the peripheral veins. Consequently, even very
venous return curve, as we explain in the next sections. negative pressures in the right atrium cannot increase

251
UNIT IV The Circulation

venous return significantly above that which exists at a chambers of the heart. Therefore, the capacity of the sys-
normal atrial pressure of 0 mm Hg. tem decreases so that at each level of blood volume, the
mean circulatory filling pressure is increased. At normal
Mean Circulatory Filling Pressure, Mean blood volume, maximal sympathetic stimulation increas-
Systemic Filling Pressure—Effects on es the mean circulatory filling pressure from 7 mm Hg to
Venous Return about twice that value or about 14 mm Hg.
When heart pumping is stopped by shocking the heart Conversely, complete inhibition of the sympathetic
with electricity to cause ventricular fibrillation or is nervous system relaxes both the blood vessels and heart,
stopped in any other way, flow of blood everywhere in decreasing the mean circulatory filling pressure from the
the circulation ceases a few seconds later. Without blood normal value of 7 mm Hg down to about 4 mm Hg. Note
flow, the pressures everywhere in the circulation become in Figure 20-­11 how steep the curves are, which means
equal. This equilibrated pressure level is called the mean that even slight changes in blood volume or capacity of the
circulatory filling pressure. system caused by various levels of sympathetic activity can
have large effects on the mean circulatory filling pressure.
Increased Blood Volume Raises Mean Circulatory Filling
Pressure. The greater the volume of blood in the circula- Mean Systemic Filling Pressure and Relationship to
tion, the greater is the mean circulatory filling pressure Mean Circulatory Filling Pressure. The mean systemic
because extra blood volume stretches the walls of the filling pressure (Psf ) is slightly different from the mean
vasculature. The red curve in Figure 20-­11 shows the ap- circulatory filling pressure. It is the pressure measured
proximate normal effect of different levels of blood vol- everywhere in the systemic circulation after blood flow
ume on the mean circulatory filling pressure. Note that has been stopped by clamping the large blood vessels at
at a blood volume of about 4000 ml, the mean circula- the heart, so the pressures in the systemic circulation can
tory filling pressure is close to zero because this is the un- be measured independently from those in the pulmonary
stressed volume of the circulation but, at a volume of 5000 circulation. The mean systemic filling pressure, although
ml, the filling pressure is the normal value of 7 mm Hg. almost impossible to measure in a live animal, is almost
Similarly, at still higher volumes, the mean circulatory fill- always nearly equal to the mean circulatory filling pres-
ing pressure increases almost linearly. sure, because the pulmonary circulation has less than
one-eighth as much capacitance as the systemic circula-
Sympathetic Nervous Stimulation Increases Mean tion and only about one-tenth as much blood volume.
Circulatory Filling Pressure. The green curve and blue
curve in Figure 20-­11 show the effects, respectively, of Effect on Venous Return Curve of Changes in Mean
high and low levels of sympathetic nervous activity on Systemic Filling Pressure. Figure 20-­12 shows the ef-
the mean circulatory filling pressure. Strong sympathetic fects on the venous return curve caused by increasing or
stimulation constricts all the systemic blood vessels, as decreasing Psf. Note that the normal Psf is about 7 mm
well as the larger pulmonary blood vessels and even the Hg. Then, for the uppermost curve in the figure, Psf has
been increased to 14 mm Hg and, for the lowermost curve,
it has decreased to 3.5 mm Hg. These curves demonstrate
Strong sympathetic
stimulation that the higher the Psf (which also means the greater the
14
“tightness” with which the circulatory system is filled with
Mean circulatory filling pressure (mm Hg)

Normal circulatory
system blood), the more the venous return curve shifts upward
12
Complete sympathetic and to the right. Conversely, the lower the Psf, the more
inhibition the curve shifts downward and to the left.
10
Normal volume

8
Venous return (L/min)

10
6 Psf = 3.5
Psf = 7
4 5 No Psf = 14
rm
al
2
0
0 –4 0 +4 +8 +12
0 1000 2000 3000 4000 5000 6000 7000 Right atrial pressure (mm Hg)
Volume (milliliters) Figure 20-­12. Venous return curves showing the normal curve when
Figure 20-­11. Effect of changes in total blood volume on the mean the mean systemic filling pressure (Psf) is 7 mm Hg and the effect of
circulatory filling pressure (volume-­pressure curve for the entire circulatory altering the Psf to 3.5, 7, or 14 mm Hg. (Modified from Guyton AC,
system). These curves also show the effects of strong sympathetic Jones CE, Coleman TG: Circulatory Physiology: Cardiac Output and Its
stimulation and complete sympathetic inhibition. Regulation, 2nd ed. Philadelphia: WB Saunders, 1973.)

252
 Chapter 20 Cardiac Output, Venous Return, and Their Regulation

Expressing this another way, the greater the degree to 20

which the system is filled, the easier it is for blood to flow
into the heart. The lesser the degree to which the system is
filled, the more difficult it is for blood to flow into the heart.
15

Venous return (L/min)

UNIT IV
When Pressure Gradient for Venous Return Is Zero
There Is No Venous Return. When the right atrial pres-
sure rises to equal the Psf, there is no longer any pres-

1/
10

2
sure difference between the peripheral vessels and right

re
sis
atrium. Consequently, there can no longer be any blood

ta
n
ce
Norm
flow from peripheral vessels back to the right atrium. al r
es
However, when the right atrial pressure falls progressive- 5 ista
nc Psf = 7
ly lower than the Psf, blood flow to the heart increases 2  resis e
tance
proportionately, as can be seen by studying any of the ve-
nous return curves in Figure 20-­12. That is, the greater
0
the difference between the Psf and right atrial pressure, the –4 0 +4 +8
greater becomes the venous return. Therefore, the differ- Right atrial pressure (mm Hg)
ence between these two pressures is called the pressure Figure 20-­13. Venous return curves depicting the effect of altering
gradient for venous return. the resistance to venous return. Psf, Mean systemic filling pressure.
(Modified from Guyton AC, Jones CE, Coleman TG: Circulatory Physi-
Resistance to Venous Return ology: Cardiac Output and Its Regulation, 2nd ed. Philadelphia: WB
In the same way that Psf represents a pressure pushing Saunders, 1973.)
venous blood from the periphery toward the heart, there
is also resistance to this venous flow of blood. This is called Effect of Resistance to Venous Return on the Venous
the resistance to venous return. Most of the resistance to Return Curve. Figure 20-­13 demonstrates the effect
venous return occurs in the veins, although some occurs of different levels of resistance to venous return on the
in the arterioles and small arteries as well. venous return curve, showing that a decrease in this
Why is venous resistance so important in determining resistance to half-­normal allows twice as much flow of
the resistance to venous return? The answer is that when blood and, therefore, rotates the curve upward to twice
the resistance in the veins increases, blood begins to be as great a slope. Conversely, an increase in resistance
dammed up, mainly in the veins themselves. However, to twice normal rotates the curve downward to half as
the venous pressure rises very little because the veins are great a slope.
highly distensible. Therefore, this rise in venous pressure is Note also that when the right atrial pressure rises to
not very effective in overcoming the resistance, and blood equal the Psf, venous return becomes zero at all levels of
flow into the right atrium decreases drastically. Conversely, resistance to venous return because there is no pressure
when arteriolar and small artery resistances increase, blood gradient to cause flow of blood. Therefore, the highest
accumulates in the arteries, which have a capacitance only level to which the right atrial pressure can rise, regardless
one thirtieth as great as that of the veins. Therefore, even of how much the heart might fail, is equal to the Psf.
slight accumulation of blood in the arteries raises the pres-
Combinations of Venous Return Curve Patterns. Fig-
sure greatly—30 times as much as in the veins—and this
ure 20-­14 shows the effects on the venous return curve
high pressure overcomes much of the increased resistance.
caused by simultaneous changes in Psf and resistance to
Mathematically, it turns out that about two-thirds of the
venous return, demonstrating that both these factors can
so-­called resistance to venous return is determined by
operate simultaneously.
venous resistance, and about one-third is determined by
the arteriolar and small artery resistance.
ANALYSIS OF CARDIAC OUTPUT
Venous return can be calculated by the following
AND RIGHT ATRIAL PRESSURE BY
formula:
SIMULTANEOUS CARDIAC OUTPUT AND
Psf − PRA
VR = VENOUS RETURN CURVES
RVR
In the complete circulation, the heart and the systemic
in which VR is venous return, Psf is mean systemic filling circulation must operate together. This requirement
pressure, PRA is right atrial pressure, and RVR is resis- means that (1) the venous return from the systemic circu-
tance to venous return. In the healthy adult, the approxi- lation must equal the cardiac output from the heart and
mate values for these are as follows: venous return = 5 (2) the right atrial pressure is the same for the heart and
L/min, Psf = 7 mm Hg, right atrial pressure = 0 mm Hg, systemic circulation.
and resistance to venous return = 1.4 mm Hg/L/min of Therefore, one can predict the cardiac output and right
blood flow. atrial pressure in the following way:

253
UNIT IV The Circulation

Normal resistance
heart and systemic circulation. Therefore, in the normal
15
circulation, the right atrial pressure, cardiac output, and
2  resistance
1/2 resistance
venous return are all depicted by point A, called the equi-
librium point, giving a normal value for cardiac output of
Venous return (L/min)

1/3 resistance
5 L/min and a right atrial pressure of 0 mm Hg.
10
Effect of Increased Blood Volume on Cardiac Output.
A sudden increase in blood volume of about 20% increas-
es the cardiac output to about 2.5 to 3 times normal. An
5
Psf = 10.5 analysis of this effect is shown in Figure 20-­15. Imme-
Psf = 10 diately on infusing the large quantity of extra blood, the
Psf = 2.3 increased filling of the system causes the Psf to increase
Psf = 7 to 16 mm Hg, which shifts the venous return curve to
0
–4 0 +4 +8 +12 the right. At the same time, the increased blood volume
Right atrial pressure (mm Hg) distends the blood vessels, reducing their resistance and
Figure 20-­14. Combinations of the major patterns of venous return thereby reducing the resistance to venous return, which
curves showing the effects of simultaneous changes in the mean sys- rotates the curve upward. As a result of these two effects,
temic filling pressure (Psf) and in resistance to venous return. (Modi- the venous return curve of Figure 20-­15 is shifted to the
fied from Guyton AC, Jones CE, Coleman TG: Circulatory Physiology: right. This new curve equates with the cardiac output
Cardiac Output and Its Regulation, 2nd ed. Philadelphia: WB Saun-
ders, 1973.)
curve at point B, showing that the cardiac output and ve-
nous return increase 2.5 to 3 times and that the right atrial
pressure rises to about +8 mm Hg.
Cardiac output and venous return (L/min)

20
Compensatory Effects Initiated in Response to Increased
Blood Volume. The greatly increased cardiac output
15 caused by increased blood volume lasts for only a few
B minutes because several compensatory effects immedi-
ately begin to occur:
10 1. The increased cardiac output increases the capillary
pressure so that fluid begins to transude out of the
A capillaries into the tissues, thereby returning the
5 Psf = 7 Psf = 16
blood volume toward normal.
2. The increased pressure in the veins causes the veins
0 to continue distending gradually by the mechanism
−4 0 +4 +8 +12 +16 called stress-­relaxation, especially causing the ve-
Right atrial pressure (mm Hg) nous blood reservoirs, such as the liver and spleen,
Figure 20-­15. The two solid curves demonstrate an analysis of car- to distend, thus reducing the Psf.
diac output and right atrial pressure when the cardiac output (red 3. The excess blood flow through the peripheral tissues
line) and venous return (blue line) curves are normal. Transfusion of causes an autoregulatory increase in the peripheral
blood equal to 20% of the blood volume causes the venous return vascular resistance, thus increasing the resistance to
curve to become the dashed curve. As a result, the cardiac output
venous return.
and right atrial pressure shift from point A to point B. Psf, Mean
systemic filling pressure. These factors cause the Psf to return toward normal
and the resistance vessels of the systemic circulation to
constrict. Therefore, gradually, over a period of 10 to 40
1. Determine the momentary pumping ability of the minutes, the cardiac output returns almost to normal.
heart, and depict this ability in the form of a cardiac
output curve. Effect of Sympathetic Stimulation on Cardiac Output.
2. Determine the momentary state of flow from the Sympathetic stimulation affects the heart and systemic
systemic circulation into the heart, and depict this circulation: (1) it makes the heart a stronger pump; and (2)
state of flow in the form of a venous return curve. in the systemic circulation, it increases the Psf because of
3. Equate these curves against each other, as shown in contraction of the peripheral vessels, especially the veins,
Figure 20-­15. and it increases the resistance to venous return.
Two curves in the figure depict the normal cardiac out- In Figure 20-­16, the normal cardiac output and
put curve (red line) and the normal venous return curve venous return curves are depicted; these equate with
(blue line). There is only one point on the graph, point A, each other at point A, which represents a normal venous
at which the venous return equals the cardiac output and return, cardiac output of 5 L/min. and right atrial pressure
at which the right atrial pressure is the same for both the of 0 mm Hg. Note in the figure that maximal sympathetic

254
 Chapter 20 Cardiac Output, Venous Return, and Their Regulation

Maximal sympathetic D
25 20
stimulation

Cardiac output and venous return (L/min)

Cardiac output and venous return (L/min)

Moderate sympathetic C
20 stimulation
15
B

UNIT IV
15
Normal
Spinal anesthesia 10
10 D

C
A A
5 5

B
0
−4 0 +4 +8 +12 +16 0
Right atrial pressure (mm Hg) −4 0 +4 +8 +12

Figure 20-­16. Analysis of the effect on cardiac output of (1) moder- Right atrial pressure (mm Hg)
ate sympathetic stimulation (from point A to point C), (2) maximal Figure 20-­17. Analysis of successive changes in cardiac output and
sympathetic stimulation (point D), and (3) sympathetic inhibition right atrial pressure in a human after a large arteriovenous (AV) fis-
caused by total spinal anesthesia (point B). (Modified from Guyton tula is suddenly opened. The stages of the analysis, as shown by the
AC, Jones CE, Coleman TG: Circulatory Physiology: Cardiac Output equilibrium points, are as follows: A, normal conditions; B, immedi-
and Its Regulation, 2nd ed. Philadelphia: WB Saunders, 1973.) ately after opening the AV fistula; C, 1 minute or so after the sym-
pathetic reflexes have become active; and D, several weeks after the
blood volume has increased and the heart has begun to hypertrophy.
stimulation (green curves) increases the Psf to 17 mm Hg (Modified from Guyton AC, Jones CE, Coleman TG: Circulatory Physi-
(depicted by the point at which the venous return curve ology: Cardiac Output and Its Regulation, 2nd ed. Philadelphia: WB
reaches the zero venous return level). Sympathetic stimu- Saunders, 1973.)
lation also increases pumping effectiveness of the heart
by nearly 100%. As a result, the cardiac output rises from The principal effects are as follows: (a) a sudden and
the normal value at equilibrium point A to about double precipitous rotation of the venous return curve up-
normal at equilibrium point D, and yet the right atrial ward caused by the large decrease in resistance to
pressure hardly changes. Thus, different degrees of sym- venous return when blood is allowed to flow with
pathetic stimulation can increase the cardiac output pro- almost no impediment directly from the large arter-
gressively to about twice normal for short periods, until ies into the venous system, bypassing most of the
other compensatory effects occur within seconds or min- resistance elements of the peripheral circulation;
utes to return cardiac output to nearly normal. and (b) a slight increase in the level of the cardiac
output curve because opening the fistula decreases
Effect of Sympathetic Inhibition on Cardiac Output. the peripheral resistance and allows an acute fall in
The sympathetic nervous system can be blocked by in- arterial pressure against which the heart can pump
ducing total spinal anesthesia or by using a drug, such as more easily. The net result, depicted by point B, is
hexamethonium, that blocks transmission of nerve signals an increase in cardiac output from 5 L/min up to
through the autonomic ganglia. The lowermost curves in 13 L/min and an increase in right atrial pressure to
Figure 20-­16 show the effect of sympathetic inhibition about +3 mm Hg.
caused by total spinal anesthesia, demonstrating the fol- 3. Point C represents the effects about 1 minute later,
lowing: (1) the Psf falls to about 4 mm Hg; and (2) the ef- after the sympathetic nerve reflexes have restored
fectiveness of the heart as a pump decreases to about 80% the arterial pressure almost to normal and caused
of normal. The cardiac output falls from point A to point two other effects: (a) an increase in the Psf (because
B, which is a decrease to about 60% of normal. of constriction of all veins and arteries) from 7 to
9 mm Hg, thus shifting the venous return curve 2
Effect of Opening a Large Arteriovenous Fistula. Fig- mm Hg to the right; and (b) further elevation of the
ure 20-­17 shows various stages of circulatory changes cardiac output curve because of sympathetic nerv-
that occur after opening a large AV fistula—that is, after ous excitation of the heart. The cardiac output now
making an opening directly between a large artery and a rises to almost 16 L/min, and the right atrial pres-
large vein. sure rises to about 4 mm Hg.
1. The two red curves crossing at point A show the 4. Point D shows the effect after several more weeks.
normal condition. By this time, the blood volume has increased be-
2. The curves crossing at point B show the circulatory cause the slight reduction in arterial pressure and
condition immediately after opening the large fistula. the sympathetic stimulation have both transiently

255
UNIT IV The Circulation

reduced the kidney output of urine, causing salt oxygen concentration of 160 ml/L of blood, whereas that
and water retention. The Psf has now risen to +12 leaving the left heart has an oxygen concentration of 200
mm Hg, shifting the venous return curve another 3 ml/L of blood. From these data, one can calculate that
mm Hg to the right. Also, the prolonged increased each liter of blood passing through the lungs absorbs 40 ml
workload on the heart has caused the heart muscle of oxygen.
to hypertrophy slightly, raising the level of the car- Because the total quantity of oxygen absorbed into the
diac output curve still further. Therefore, point D blood from the lungs each minute is 200 ml, dividing 200
shows a cardiac output that is now almost 20 L/min by 40 calculates to a total of 5 liters of blood that must
and a right atrial pressure of about 6 mm Hg. pass through the pulmonary circulation each minute to
absorb this amount of oxygen. Therefore, the quantity of
Other Analyses of Cardiac Output Regulation.
blood flowing through the lungs each minute is 5 liters,
In Chapter 21, analysis of cardiac output regulation dur-
which is also a measure of the cardiac output. Thus, the
ing exercise is presented. In Chapter 22, analyses of cardi-
cardiac output can be calculated by the following formula:
ac output regulation at various stages of congestive heart
failure are discussed. Cardiac output (L min )
O absorbed per minute by the lungs (ml min)
= 2
Arteriovenous O2 difference (ml L of blood)
METHODS FOR MEASURING CARDIAC
OUTPUT
In applying this Fick procedure for measuring cardiac
Accurate assessment of cardiac output is vitally impor- output in humans, mixed venous blood is usually obtained
tant in modern medical practice, especially in critically through a catheter inserted up the brachial vein of the
ill patients or in high-­risk patients undergoing surgery. In forearm, through the subclavian vein, down to the right
animal experiments, one can measure the cardiac output atrium and, finally, into the right ventricle or pulmonary
using an electromagnetic or ultrasonic flowmeter placed artery. Systemic arterial blood can then be obtained from
on the aorta or pulmonary artery to measure cardiac out- any systemic artery in the body. The rate of oxygen absorp-
put. In humans, however, cardiac output is usually mea- tion by the lungs is measured by the rate of disappearance
sured by indirect methods that do not require surgery. of oxygen from the respired air, using any type of oxygen
meter.
Pulsatile Output of the Heart Measured
by Electromagnetic or Ultrasonic Indicator Dilution Method
Flowmeter To measure cardiac output by the indicator dilution
Figure 20-­18 shows a recording in a dog of blood flow method, a small amount of indicator, such as a dye, is
in the root of the aorta; this recording was made using injected into a large systemic vein or, preferably, into the
an electromagnetic flowmeter. It demonstrates that the right atrium. This indicator passes rapidly through the
blood flow rises rapidly to a peak during systole and then, right side of the heart, then through the blood vessels of
at the end of systole, it reverses for a fraction of a second. the lungs, through the left side of the heart, and finally into
This reverse flow causes the aortic valve to close and the the systemic arterial system. The concentration of the dye
flow to return to zero. is recorded as the dye passes through one of the periph-
eral arteries, giving a curve as shown in Figure 20-­20. In
Measurement of Cardiac Output Using each of these cases, 5 milligrams of Cardiogreen dye were
the Oxygen Fick Principle injected at zero time. In the top recording, none of the dye
The Fick principle is explained by Figure 20-­19. This passed into the arterial tree until about 3 seconds after the
figure shows that 200 ml of oxygen are being absorbed injection, but then the arterial concentration of the dye
from the lungs into the pulmonary blood each minute. It
also shows that the blood entering the right heart has an
LUNGS

20
Flow (L/min)

15 Oxygen used = 200 ml/min

10
5
0
Cardiac output =
O2 = 5000 ml/min O2 =
0 1 2 160 ml/L 200 ml/L
Seconds right heart left heart
Figure 20-­18. Pulsatile blood flow in the root of the aorta recorded
using an electromagnetic flowmeter. Figure 20-­19. Fick principle for determining cardiac output.

256
 Chapter 20 Cardiac Output, Venous Return, and Their Regulation

5 mg Cardiac output (ml min ) =

injected
Milligrams of dye injected × 60
 Average concentration of dye  Duration of 
Dye concentration in artery (mg/100 ml)
0.5
0.4  in each milliliter of blood  ×  the curve 
0.3  for the du
uration of the curve   in seconds 
0.2

UNIT IV
0.1
0 Echocardiography
0 10 20 30
5 mg
Cardiac output can also be estimated by echocardiogra-
0.5 injected phy, a method that uses ultrasound waves from a trans-
0.4 ducer placed on the chest wall or passed into the patient’s
0.3 esophagus to measure the size of the heart’s chambers and
0.2 the velocity of blood flowing from the left ventricle into
0.1
the aorta. Stroke volume is calculated from the velocity of
0
0 10 20 30 blood flowing into the aorta, and the aorta cross-­sectional
Seconds area is determined from the aorta diameter measured by
Figure 20-­20. Extrapolated dye concentration curves used to calcu-
ultrasound imaging. Cardiac output is then calculated
late two separate cardiac outputs by the dilution method. The rectan- from the product of the stroke volume and heart rate.
gular areas are the calculated average concentrations of dye in the
arterial blood for the durations of the respective extrapolated curves. Thoracic Electrical Bioimpedance Method
Impedance cardiography, also known as thoracic elec-
rose rapidly to a maximum in about 6 to 7 seconds. After trical bioimpedance, is a noninvasive technology used
that, the concentration fell rapidly, but before the concen- to measure changes in total electrical conductivity of
tration reached zero, some of the dye had already circu- the thorax as an indirect assessment of hemodynamic
lated all the way through some of the peripheral systemic parameters such as cardiac output. This method detects
vessels and returned through the heart for a second time. the impedance changes caused by a high-­frequency, low-­
Consequently, the dye concentration in the artery began magnitude current flowing through the thorax between
to rise again. For the purpose of calculation, it is neces- additional two pairs of electrodes located outside the
sary to extrapolate the early downslope of the curve to the measured segment. Electrical impedance is the opposi-
zero point, as shown by the dashed portion of each curve. tion that a circuit presents to a current when a voltage is
In this way, the extrapolated time-­concentration curve of applied. With each heartbeat, blood volume and veloc-
the dye in the systemic artery without recirculation can ity in the aorta change, and the corresponding change
be measured in its first portion and estimated reasonably in impedance and its timing are measured and used to
accurately in its latter portion. estimate cardiac output.
Once the extrapolated time-­concentration curve has Although some studies have suggested that imped-
been determined, the mean concentration of dye in the ance cardiography may provide reasonable assessments
arterial blood for the duration of the curve can then be of cardiac output under some conditions, this method is
calculated. For example, in the top example of Figure also subject to several potential sources of error, including
20-­20, this calculation was done by measuring the area electrical interferences, motion artifacts, fluid accumula-
under the entire initial and extrapolated curve and then tion around the heart and in the lungs, and arrhythmias.
averaging the concentration of dye for the duration of Some studies have suggested that the average error with
the curve. One can see from the shaded rectangle strad- this method may be as high as 20% to 40%.
dling the curve in the upper figure that the average con- Accurate assessment of cardiac output provides insight
centration of dye was 0.25 mg/dl of blood and that the into heart function and tissue perfusion because cardiac
duration of this average value was 12 seconds. A total of output represents the sum of blood flows to all the organs
5 milligrams of dye had been injected at the beginning and tissues of the body. Thus, noninvasive methods for
of the experiment. For blood carrying only 0.25 milli- more accurate measurements of cardiac output are con-
gram of dye in each 100 milliliters to carry the entire tinuously being developed for managing patients with cir-
5 milligrams of dye through the heart and lungs in 12 culatory distress.
seconds, a total of 20 portions, each with 100 milliliters
of blood, would have passed through the heart during Bibliography
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257
UNIT IV The Circulation

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258