CHAPTER 9

UNIT III
Cardiac Muscle; The Heart as a Pump and
Function of the Heart Valves

The heart, shown in Figure 9-­1, is actually two separate again. Note that cardiac muscle is striated in the same
pumps, a right heart that pumps blood through the lungs manner as in skeletal muscle. Furthermore, cardiac mus-
and a left heart that pumps blood through the systemic cle has typical myofibrils that contain actin and myosin
circulation that provides blood flow to the other organs filaments almost identical to those found in skeletal mus-
and tissues of the body. Each of these is a pulsatile, two-­ cle; these filaments lie side by side and slide during con-
chamber pump composed of an atrium and a ventricle. traction in the same manner as occurs in skeletal muscle
Each atrium is a weak primer pump for the ventricle, (see Chapter 6). In other ways, however, cardiac muscle is
helping to move blood into the ventricle. The ventricles quite different from skeletal muscle, as we shall see.
then supply the main pumping force that propels the
Left Ventricular Rotation (Twist) Aids Left Ventricular
blood either (1) through the pulmonary circulation by the
Ejection and Relaxation. The left ventricle is organized
right ventricle or (2) through the systemic circulation by
into complex muscle fiber layers that run in different di-
the left ventricle. The heart is surrounded by a two-­layer
rections and allow the heart to contract in a twisting mo-
sac called the pericardium, which protects the heart and
tion during systole. The subepicardial (outer) layer spirals
holds it in place.
in a leftward direction, and the subendocardial (inner)
Special mechanisms in the heart cause a continuing
layer spirals in the opposite direction (rightward), causing
succession of contractions called cardiac rhythmicity,
clockwise rotation of the apex of the heart and counter-
transmitting action potentials throughout the cardiac
clockwise rotation of the base of the left ventricle (Figure
muscle to cause the heart’s rhythmical beat. This rhyth-
9-­3). This causes a wringing motion of the left ventricle,
mical control system is discussed in Chapter 10. In this
pulling the base downward toward the apex during sys-
chapter, we explain how the heart operates as a pump,
tole (contraction). At the end of systole, the left ventricle
beginning with the special features of cardiac muscle
is similar to a loaded spring and recoils or untwists during
(Video 9-­1).
diastole (relaxation) to allow blood to enter the pumping
chambers rapidly.
PHYSIOLOGY OF CARDIAC MUSCLE
Cardiac Muscle Is a Syncytium. The dark areas crossing
The heart is composed of three major types of cardiac the cardiac muscle fibers in Figure 9-­2 are called interca-
muscle—atrial muscle, ventricular muscle, and special- lated discs; they are actually cell membranes that separate
ized excitatory and conductive muscle fibers. The atrial individual cardiac muscle cells from one another. That is,
and ventricular types of muscle contract in much the cardiac muscle fibers are made up of many individual cells
same way as skeletal muscle, except that the duration of connected in series and in parallel with one another.
contraction is much longer. The specialized excitatory At each intercalated disc, the cell membranes fuse with
and conductive fibers of the heart, however, contract fee- one another to form permeable communicating junctions
bly because they contain few contractile fibrils; instead, (gap junctions) that allow rapid diffusion of ions. There-
they exhibit automatic rhythmical electrical discharge in fore, from a functional point of view, ions move with ease
the form of action potentials or conduction of the action in the intracellular fluid along the longitudinal axes of the
potentials through the heart, providing an excitatory sys- cardiac muscle fibers so that action potentials travel easily
tem that controls the rhythmical beating of the heart. from one cardiac muscle cell to the next, past the interca-
lated discs. Thus, cardiac muscle is a syncytium of many
heart muscle cells in which the cardiac cells are so inter-
CARDIAC MUSCLE ANATOMY
connected that when one cell becomes excited, the action
Figure 9-­2 shows the cardiac muscle histology, demon- potential rapidly spreads to all of them.
strating cardiac muscle fibers arranged in a latticework, The heart actually is composed of two syncytia; the
with the fibers dividing, recombining, and then spreading atrial syncytium, which constitutes the walls of the two

113
UNIT III The Heart

HEAD AND UPPER EXTREMITY Endocardial fibers

Base

Aorta
Pulmonary artery
Superior
Lungs
vena cava

Right atrium Pulmonary

Pulmonary veins
valve Left atrium
Mitral valve Epicardial fibers Apex
Tricuspid
valve Aortic valve A B
Right ventricle Left Figure 9-­3. A, The left ventricular inner subendocardial fibers (laven-
ventricle der shade) run obliquely to the outer subepicardial fibers (red shade).
Inferior
vena cava B, The subepicardial muscle fibers are wrapped in a left-­handed helix
and subendocardial fibers are arranged in a right-­handed helix.

TRUNK AND Plateau

LOWER EXTREMITY
+20
0
Endocardium
–20
Myocardium –40
–60
Epicardium –80
Pericardium Pericardial space –100 Purkinje fiber
Millivolts

Parietal pericardium Plateau

Fibrous pericardium +20
Figure 9-­1. Structure of the heart and course of blood flow through 0
the heart chambers and heart valves. The heart consists of multiple –20
layers, including the inner endocardium, myocardium, and more out- –40
ward epicardium and pericardium layers. –60
–80
–100 Ventricular muscle

0 1 2 3 4
Seconds
Figure 9-­4. Rhythmical action potentials (in millivolts) from a Purkin-
je fiber and from a ventricular muscle fiber, recorded by microelec-
trodes.
Intercalated discs

fibers several millimeters in diameter that is discussed in

Chapter 10.
This division of the muscle of the heart into two func-
tional syncytia allows the atria to contract a short time
ahead of ventricular contraction, which is important for
the effectiveness of heart pumping.

Figure 9-­2. Syncytial interconnecting nature of cardiac muscle fibers.

ACTION POTENTIALS IN CARDIAC
MUSCLE
atria; and the ventricular syncytium, which constitutes
the walls of the two ventricles. The atria are separated The action potential recorded in a ventricular muscle
from the ventricles by fibrous tissue that surrounds the fiber, shown in Figure 9-­4, averages about 105 millivolts,
atrioventricular (A-­V ) valvular openings between the which means that the intracellular potential rises from a
atria and ventricles. Normally, potentials are not con- very negative value between beats, about −85 millivolts,
ducted from the atrial syncytium into the ventricular to a slightly positive value, about +20 millivolts, during
syncytium directly through this fibrous tissue. Instead, each beat. After the initial spike, the membrane remains
they are only conducted by way of a specialized conduc- depolarized for about 0.2 second, exhibiting a plateau, fol-
tive system called the A-­V bundle, a bundle of conductive lowed at the end of the plateau by abrupt repolarization.

114
 Chapter 9 Cardiac Muscle: The Heart as a Pump and Function of the Heart Valves

The presence of this plateau in the action potential causes

ventricular contraction to last as much as 15 times longer 20
1
in cardiac muscle than in skeletal muscle.

Membrane potential (millivolts)

2
0
What Causes the Long Action Potential and Plateau in

UNIT III
Cardiac Muscle? At least two major differences between -20
the membrane properties of cardiac and skeletal muscle ac-
count for the prolonged action potential and the plateau in -40 0 3
cardiac muscle. First, the action potential of skeletal muscle
is caused almost entirely by the sudden opening of large -60

numbers of fast sodium channels that allow tremendous

-80
numbers of sodium ions to enter the skeletal muscle fiber 4 4
from the extracellular fluid. These channels are called fast
-100
channels because they remain open for only a few thou-
0 100 200 300
sandths of a second and then abruptly close. At the end of
Time (milliseconds)
this closure, repolarization occurs, and the action potential
is over within about another thousandth of a second.
In cardiac muscle, the action potential is caused by Outward iK+
opening of two types of channels: (1) the same voltage-­
activated fast sodium channels as those in skeletal muscle; Ionic
and (2) another entirely different population of L-­type currents
calcium channels (slow calcium channels), which are also Inward iCa2+
called calcium-­sodium channels. This second population of
channels differs from the fast sodium channels in that they
are slower to open and, even more importantly, remain
iNa+
open for several tenths of a second. During this time, a large
quantity of both calcium and sodium ions flows through Figure 9-­5. Phases of action potential of cardiac ventricular muscle
these channels to the interior of the cardiac muscle fiber, cell and associated ionic currents for sodium (iNa+), calcium (iCa2+),
and this activity maintains a prolonged period of depolar- and potassium (iK+).
ization, causing the plateau in the action potential. Fur-
thermore, the calcium ions that enter during this plateau Phase 0 (Depolarization): Fast Sodium Channels
phase activate the muscle contractile process, whereas the Open. When the cardiac cell is stimulated and depolar-
calcium ions that cause skeletal muscle contraction are izes, the membrane potential becomes more positive.
derived from the intracellular sarcoplasmic reticulum. Voltage-­gated sodium channels (fast sodium channels)
The second major functional difference between car- open and permit sodium to rapidly flow into the cell and
diac muscle and skeletal muscle that helps account for depolarize it. The membrane potential reaches about +20
both the prolonged action potential and its plateau is that millivolts before the sodium channels close.
immediately after the onset of the action potential, the Phase 1 (Initial Repolarization): Fast Sodium Chan-
permeability of the cardiac muscle membrane for potas- nels Close. The sodium channels close, the cell begins to
sium ions decreases about fivefold, an effect that does not repolarize, and potassium ions leave the cell through open
occur in skeletal muscle. This decreased potassium perme- potassium channels.
ability may result from the excess calcium influx through Phase 2 (Plateau): Calcium Channels Open and Fast
the calcium channels just noted. Regardless of the cause, Potassium Channels Close. A brief initial repolarization
the decreased potassium permeability greatly decreases occurs and the action potential then plateaus as a result
the efflux of positively charged potassium ions during the of increased calcium ion permeability and decreased po-
action potential plateau and thereby prevents early return tassium ion permeability. The voltage-­gated calcium ion
of the action potential voltage to its resting level. When the channels open slowly during phases 1 and 0, and calcium
slow calcium-­sodium channels do close at the end of 0.2 enters the cell. Potassium channels then close, and the
to 0.3 second, and the influx of calcium and sodium ions combination of decreased potassium ion efflux and in-
ceases, the membrane permeability for potassium ions also creased calcium ion influx causes the action potential to
increases rapidly. This rapid loss of potassium from the plateau.
fiber immediately returns the membrane potential to its Phase 3 (Rapid Repolarization): Calcium Channels
resting level, thus ending the action potential. Close and Slow Potassium Channels Open. The closure
of calcium ion channels and increased potassium ion
Phases of Cardiac Muscle Action Potential. Figure 9-­5 permeability, permitting potassium ions to exit the cell
summarizes the phases of the action potential in cardiac rapidly, ends the plateau and returns the cell membrane
muscle and the ion flows that occur during each phase. potential to its resting level.

115
UNIT III The Heart

Refractory period discussed for skeletal muscle in Chapter 7. Again, there

Relative refractory
are differences in this mechanism in cardiac muscle that
Later premature have important effects on the characteristics of heart
Force of contraction

period
contraction muscle contraction.
Early premature
contraction As is true for skeletal muscle, when an action poten-
tial passes over the cardiac muscle membrane, the action
potential spreads to the interior of the cardiac muscle
fiber along the membranes of the transverse (T) tubules.
The T tubule action potentials then act on the membranes
of the longitudinal sarcoplasmic tubules to cause release
of calcium ions into the muscle sarcoplasm from the sar-
0 1 2 3
coplasmic reticulum. In another few thousandths of a
Seconds
second, these calcium ions diffuse into the myofibrils and
Figure 9-­6. Force of ventricular heart muscle contraction, showing catalyze the chemical reactions that promote sliding of
also the duration of the refractory period and relative refractory pe-
riod, plus the effect of premature contraction. Note that premature
the actin and myosin filaments along one another, which
contractions do not cause wave summation, as occurs in skeletal produces the muscle contraction.
muscle. Thus far, this mechanism of excitation-­ contraction
coupling is the same as that for skeletal muscle, but there
Phase 4 (Resting Membrane Potential):. This averages is a second effect that is quite different. In addition to
about−80 to −90 millivolts. the calcium ions that are released into the sarcoplasm
from the cisternae of the sarcoplasmic reticulum, cal-
Velocity of Signal Conduction in Cardiac Muscle. The cium ions also diffuse into the sarcoplasm from the T
velocity of conduction of the excitatory action potential tubules at the time of the action potential, which opens
signal along both atrial and ventricular muscle fibers is voltage-­dependent calcium channels in the membrane of
about 0.3 to 0.5 m/sec, or about 1/250 the velocity in very the T tubule (Figure 9-­7). Calcium entering the cell then
large nerve fibers and about 1/10 the velocity in skeletal activates calcium release channels, also called ryanodine
muscle fibers. The velocity of conduction in the special- receptor channels, in the sarcoplasmic reticulum mem-
ized heart conductive system—in the Purkinje fibers—is brane, triggering the release of calcium into the sarco-
as high as 4 m/sec in most parts of the system, allowing plasm. Calcium ions in the sarcoplasm then interact with
rapid conduction of the excitatory signal to the different troponin to initiate cross-­bridge formation and contrac-
parts of the heart, as explained in Chapter 10. tion by the same basic mechanism as that described for
skeletal muscle in Chapter 6.
Refractory Period of Cardiac Muscle. Cardiac muscle, Without the calcium from the T tubules, the
like all excitable tissue, is refractory to restimulation dur- strength of cardiac muscle contraction would be
ing the action potential. Therefore, the refractory period reduced considerably because the sarcoplasmic reticu-
of the heart is the interval of time, as shown to the left in lum of cardiac muscle is less well developed than that
Figure 9-­6, during which a normal cardiac impulse can- of skeletal muscle and does not store enough calcium
not re-­excite an already excited area of cardiac muscle. to provide full contraction. The T tubules of cardiac
The normal refractory period of the ventricle is 0.25 to muscle, however, have a diameter five times as great
0.30 second, which is about the duration of the prolonged as that of the skeletal muscle tubules, which means a
plateau action potential. There is an additional relative volume 25 times as great. Also, inside the T tubules is
refractory period of about 0.05 second during which the a large quantity of mucopolysaccharides that are elec-
muscle is more difficult to excite than normal but can be tronegatively charged and bind an abundant store of
excited by a very strong excitatory signal, as demonstrated calcium ions, keeping them available for diffusion to
by the early premature contraction in the second example the interior of the cardiac muscle fiber when a T tubule
of Figure 9-­6. The refractory period of atrial muscle is action potential appears.
much shorter than that for the ventricles (about 0.15 sec- The strength of contraction of cardiac muscle depends
ond for the atria compared with 0.25 to 0.30 second for to a great extent on the concentration of calcium ions in
the ventricles). the extracellular fluids. In fact, a heart placed in a calcium-­
free solution will quickly stop beating. The reason for this
response is that the openings of the T tubules pass directly
EXCITATION-­CONTRACTION COUPLING—
through the cardiac muscle cell membrane into the extra-
FUNCTION OF CALCIUM IONS AND THE
cellular spaces surrounding the cells, allowing the same
TRANSVERSE TUBULES
extracellular fluid that is in the cardiac muscle intersti-
The term excitation-­contraction coupling refers to the tium to percolate through the T tubules. Consequently,
mechanism whereby the action potential causes the the quantity of calcium ions in the T tubule system (i.e.,
myofibrils of muscle to contract. This mechanism was the availability of calcium ions to cause cardiac muscle

116
 Chapter 9 Cardiac Muscle: The Heart as a Pump and Function of the Heart Valves

Extracellular
fluid
Ca2+
Ca2+ Na+ K+
Sarcolemma

UNIT III
ATP

Ca2+ Na+
Cytoplasm

Sarcoplasmic Sarcoplasmic
reticulum L-type reticulum
Ca2+ Ca2+
channel Ca2+
RyR stores

Ca2+ T Tubule ATP

spark

Ca2+ SERCA2

Ca2+
signal
Ca2+
Contraction relaxation

Figure 9-­7. Mechanisms of excitation-­contraction coupling and relaxation in cardiac muscle. ATP, Adenosine triphosphate. RyR, ryanodine
receptor Ca2+ release channel; SERCA, sarcoplasmic reticulum Ca2+-­ATPase

contraction) depends to a great extent on the extracellular and continues to contract until a few milliseconds af-
fluid calcium ion concentration. ter the action potential ends. Therefore, the duration of
In contrast, the strength of skeletal muscle contrac- contraction of cardiac muscle is mainly a function of the
tion is hardly affected by moderate changes in extracel- duration of the action potential, including the plateau—
lular fluid calcium concentration. This is because skeletal about 0.2 second in atrial muscle and 0.3 second in ven-
muscle contraction is caused almost entirely by calcium tricular muscle.
ions released from the sarcoplasmic reticulum inside the
skeletal muscle fiber.
CARDIAC CYCLE
At the end of the plateau of the cardiac action poten-
tial, the influx of calcium ions to the interior of the muscle The cardiac events that occur from the beginning of
fiber is suddenly cut off, and calcium ions in the sarco- one heartbeat to the beginning of the next are called the
plasm are rapidly pumped back out of the muscle fibers cardiac cycle. Each cycle is initiated by the spontane-
into the sarcoplasmic reticulum and T tubule–extra- ous generation of an action potential in the sinus node,
cellular fluid space. Transport of calcium back into the as explained in Chapter 10. This node is located in the
sarcoplasmic reticulum is achieved with the help of a superior lateral wall of the right atrium near the open-
calcium–adenosine triphosphatase (ATPase) pump (the ing of the superior vena cava, and the action potential
sarcoplasmic endoplasmic reticulum calcium ATPase, travels from here rapidly through both atria and then
SERCA2; see Figure 9-­7). Calcium ions are also removed through the A-­V bundle into the ventricles. Because of
from the cell by a sodium-­calcium exchanger. The sodium this special arrangement of the conducting system from
that enters the cell during this exchange is then trans- the atria into the ventricles, there is a delay of more than
ported out of the cell by the sodium-­potassium ATPase 0.1 second during passage of the cardiac impulse from
pump. As a result, the contraction ceases until a new the atria into the ventricles. This delay allows the atria
action potential comes along. to contract ahead of ventricular contraction, thereby
pumping blood into the ventricles before the strong ven-
Duration of Contraction. Cardiac muscle begins to con- tricular contraction begins. Thus, the atria act as primer
tract a few milliseconds after the action potential begins pumps for the ventricles, and the ventricles in turn

117
UNIT III The Heart

Isovolumic
relaxation
Rapid inflow Atrial systole
Isovolumic Ejection
Diastasis
contraction

120 Aortic Aortic valve

valve closes
100

Pressure (mm Hg)

opens
Aortic pressure
80
60 A-V valve
A-V valve
40 closes opens

20 Atrial pressure
a c v
0 Ventricular pressure
130
Volume (ml)

Ventricular volume
90
R
Figure 9-­8. Events of the cardiac 50
P
cycle for left ventricular function, T Electrocardiogram
showing changes in left atrial pres- Q
1st 2nd 3rd S
sure, left ventricular pressure, aortic
pressure, ventricular volume, the Phonocardiogram
electrocardiogram, and the phono-
cardiogram. A-­V, Atrioventricular. Systole Diastole Systole

provide the major source of power for moving blood Relationship of the Electrocardiogram to
through the body’s vascular system. the Cardiac Cycle
The electrocardiogram in Figure 9-­8 shows the P, Q, R, S,
Diastole and Systole and T waves, discussed in Chapters 11 and 12. These are
The total duration of the cardiac cycle, including systole electrical voltages generated by the heart and recorded
and diastole, is the reciprocal of the heart rate. For exam- by the electrocardiogram from the surface of the body.
ple, if the heart rate is 72 beats/min, the duration of the The P wave is caused by the spread of depolarization
cardiac cycle is 1/72 min/beat—about 0.0139 min/beat, or through the atria and is followed by atrial contraction,
0.833 sec/beat. which causes a slight rise in the atrial pressure curve
Figure 9-­8 shows the different events during the car- immediately after the electrocardiographic P wave.
diac cycle for the left side of the heart. The top three About 0.16 second after the onset of the P wave, the
curves show the pressure changes in the aorta, left ventri- QRS waves appear as a result of electrical depolarization
cle, and left atrium, respectively. The fourth curve depicts of the ventricles, which initiates contraction of the ven-
the changes in left ventricular volume, the fifth depicts tricles and causes the ventricular pressure to begin ris-
the electrocardiogram, and the sixth depicts a phonocar- ing. Therefore, the QRS complex begins slightly before the
diogram, which is a recording of the sounds produced by onset of ventricular systole.
the heart—mainly by the heart valves—as it pumps. It is Finally, the ventricular T wave represents the stage
especially important that the reader study this figure in of repolarization of the ventricles when the ventricular
detail and understand the causes of all the events shown. muscle fibers begin to relax. Therefore, the T wave occurs
slightly before the end of ventricular contraction.
Increasing Heart Rate Decreases Duration of Cardiac
Cycle. When heart rate increases, the duration of each The Atria Function as Primer Pumps for
cardiac cycle decreases, including the contraction and the Ventricles
relaxation phases. The duration of the action potential Blood normally flows continually from the great veins
and systole also decrease, but not by as great a percent- into the atria; about 80% of the blood flows directly
age as diastole. At a normal heart rate of 72 beats/min, through the atria into the ventricles, even before the
systole comprises about 0.4 of the entire cardiac cycle. At atria contract. Then, atrial contraction usually causes
three times the normal heart rate, systole is about 0.65 of an additional 20% filling of the ventricles. Therefore, the
the entire cardiac cycle. This means that the heart beat- atria function as primer pumps that increase the ventric-
ing very rapidly does not remain relaxed long enough to ular pumping effectiveness as much as 20%. However,
allow complete filling of the cardiac chambers before the the heart can continue to operate under most condi-
next contraction. tions even without this extra 20% effectiveness because

118
 Chapter 9 Cardiac Muscle: The Heart as a Pump and Function of the Heart Valves

it normally has the capability of pumping 300% to 400% Outflow of Blood from the Ventricles
more blood than is required by the resting body. There- During Systole
fore, when the atria fail to function, the difference is Period of Isovolumic (Isometric) Contraction. Immedi-
unlikely to be noticed unless a person exercises; then, ately after ventricular contraction begins, the ventricular
symptoms of heart failure occasionally develop, espe- pressure rises abruptly, as shown in Figure 9-­8, causing

UNIT III
cially shortness of breath. the A-­V valves to close. Then, an additional 0.02 to 0.03
   second is required for the ventricle to build up sufficient
Pressure Changes in the Atria—a, c, and v Waves. In the pressure to push the semilunar (aortic and pulmonary)
atrial pressure curve of Figure 9-­8, three minor pressure el- valves open against the pressures in the aorta and pulmo-
evations, called a, c, and v atrial pressure waves, are shown. nary artery. Therefore, during this period, contraction is
The a wave is caused by atrial contraction. Ordinarily,
occurring in the ventricles, but no emptying occurs. This
the right atrial pressure increases 4 to 6 mm Hg during atri-
al contraction, and the left atrial pressure increases about 7
period is called the period of isovolumic or isometric con-
to 8 mm Hg. traction, meaning that cardiac muscle tension is increas-
The c wave occurs when the ventricles begin to contract; ing but little or no shortening of the muscle fibers is oc-
it is caused partly by slight backflow of blood into the atria curring.
at the onset of ventricular contraction, but mainly by bulg-
ing of the A-­V valves backward toward the atria because of Period of Ejection. When the left ventricular pressure
increasing pressure in the ventricles. rises slightly above 80 mm Hg (and the right ventricular
The v wave occurs toward the end of ventricular con- pressure rises slightly above 8 mm Hg), the ventricular
traction; it results from slow flow of blood into the atria pressures push the semilunar valves open. Immediately,
from the veins while the A-­V valves are closed during ven- blood is ejected out of the ventricles into the aorta and
tricular contraction. Then, when ventricular contraction is
pulmonary artery. Approximately 60% of the blood in the
over, the A-­V valves open, allowing this stored atrial blood
to flow rapidly into the ventricles, causing the v wave to
ventricles at the end of diastole is ejected during systole;
disappear. about 70% of this portion flows out during the first third
of the ejection period, with the remaining 30% emptying
during the next two thirds. Therefore, the first third is
called the period of rapid ejection, and the last two thirds
FUNCTION OF THE VENTRICLES AS PUMPS
is called the period of slow ejection.
The Ventricles Fill with Blood During Diastole.
During ventricular systole, large amounts of blood Period of Isovolumic (Isometric) Relaxation. At the
accumulate in the right and left atria because of the end of systole, ventricular relaxation begins suddenly, al-
closed A-­V valves. Therefore, as soon as systole is lowing both the right and left intraventricular pressures to
over, and the ventricular pressures fall again to their decrease rapidly. The elevated pressures in the distended
low diastolic values, the moderately increased pres- large arteries that have just been filled with blood from
sures that have developed in the atria during ven- the contracted ventricles immediately push blood back
tricular systole immediately push the A-­V valves open toward the ventricles, which snaps the aortic and pulmo-
and allow blood to flow rapidly into the ventricles, as nary valves closed. For another 0.03 to 0.06 second, the
shown by the rise of the left ventricular volume curve ventricular muscle continues to relax, even though the
in Figure 9-­8. This period is called the period of rapid ventricular volume does not change, giving rise to the pe-
filling of the ventricles. riod of isovolumic or isometric relaxation. During this pe-
In a healthy heart, the period of rapid filling lasts for riod, the intraventricular pressures rapidly decrease back
about the first third of diastole. During the middle third of to their low diastolic levels. Then, the A-­V valves open to
diastole, only a small amount of blood normally flows into begin a new cycle of ventricular pumping.
the ventricles. This is blood that continues to empty into the
atria from the veins and passes through the atria directly End-­
Diastolic Volume, End-­Systolic Volume, and
into the ventricles. During the last third of diastole, the atria Stroke Volume Output. During diastole, normal filling
contract and give an additional thrust to the inflow of blood of the ventricles increases the volume of each ventricle
into the ventricles. This mechanism accounts for about 20% to about 110 to 120 ml. This volume is called the end-­
of the filling of the ventricles during each heart cycle. diastolic volume. Then, as the ventricles empty during sys-
The ventricles stiffen with aging or diseases that tole, the volume decreases by about 70 ml, which is called
cause cardiac fibrosis such as high blood pressure or the stroke volume output. The remaining volume in each
diabetes mellitus. This causes less blood to fill the ventricle, about 40 to 50 ml, is called the end-­systolic vol-
ventricles in the early portion of diastole and requires ume. The fraction of the end-­diastolic volume that is eject-
more volume (preload; discussed later) or more filling ed is called the ejection fraction, usually equal to about 0.6
from the later atrial contraction to maintain adequate (or 60%). The ejection fraction percentage is often used
cardiac output. clinically to assess cardiac systolic (pumping) capability.

119
UNIT III The Heart

flow from a myocardial infarction, the valve bulges far

backward during ventricular contraction, sometimes so
MITRAL VALVE far that it leaks severely and results in severe or even lethal
cardiac incapacity.
Cusp

Aortic and Pulmonary Artery Valves. The aortic and

pulmonary artery semilunar valves function quite dif-
Chordae tendineae
ferently from the A-­V valves. First, the high pressures
in the arteries at the end of systole cause the semilunar
Papillary muscles
valves to snap closed, in contrast to the much softer
closure of the A-­V valves. Second, because of smaller
openings, the velocity of blood ejection through the
Cusp
aortic and pulmonary valves is much greater than that
through the much larger A-­V valves. Also, because of
the rapid closure and rapid ejection, the edges of the
AORTIC VALVE
aortic and pulmonary valves are subjected to much
greater mechanical abrasion than the A-­V valves. Fi-
nally, the A-­V valves are supported by the chordae
Figure 9-­9. Mitral and aortic valves (the left ventricular valves). tendineae, which is not true for the semilunar valves.
It is obvious from the anatomy of the aortic and pul-
When the heart contracts strongly, the end-­systolic monary valves (as shown for the aortic valve at the bot-
volume may decrease to as little as 10 to 20 ml. Con- tom of Figure 9-­9) that they must be constructed with
versely, when large amounts of blood flow into the ventri- an especially strong, yet very pliable, fibrous tissue to
cles during diastole, the ventricular end-­diastolic volumes withstand the extra physical stresses.
can become as much as 150 to 180 ml in the healthy heart.
By both increasing the end-­diastolic volume and decreas-
AORTIC PRESSURE CURVE
ing the end-­systolic volume, the stroke volume output can
be increased to more than double that which is normal. When the left ventricle contracts, the ventricular pressure
increases rapidly until the aortic valve opens. Then, after
the valve opens, the pressure in the ventricle rises much
THE HEART VALVES PREVENT BACKFLOW
less rapidly, as shown in Figure 9-­7, because blood imme-
OF BLOOD DURING SYSTOLE
diately flows out of the ventricle into the aorta and then
Atrioventricular Valves. The A-­V valves (i.e., the tricus- into the systemic distribution arteries.
pid and mitral valves) prevent backflow of blood from The entry of blood into the arteries during systole
the ventricles to the atria during systole, and the semilu- causes the walls of these arteries to stretch and the pres-
nar valves (i.e., the aortic and pulmonary artery valves) sure to increase to about 120 mm Hg. Next, at the end
prevent backflow from the aorta and pulmonary arteries of systole, after the left ventricle stops ejecting blood
into the ventricles during diastole. These valves, shown in and the aortic valve closes, the elastic walls of the arter-
Figure 9-­9 for the left ventricle, close and open passively. ies maintain a high pressure in the arteries, even during
That is, they close when a backward pressure gradient diastole.
pushes blood backward, and they open when a forward An incisura occurs in the aortic pressure curve when
pressure gradient forces blood in the forward direction. the aortic valve closes. This is caused by a short period of
For anatomical reasons, the thin A-­V valves require al- backward flow of blood immediately before closure of the
most no backflow to cause closure, whereas the much valve, followed by the sudden cessation of backflow.
heavier semilunar valves require rather rapid backflow for After the aortic valve closes, pressure in the aorta
a few milliseconds. decreases slowly throughout diastole because the blood
stored in the distended elastic arteries flows continually
Function of the Papillary Muscles. Figure 9-­9 also through the peripheral vessels back to the veins. Before
shows papillary muscles that attach to the vanes of the the ventricle contracts again, the aortic pressure usually
A-­V valves by the chordae tendineae. The papillary mus- has fallen to about 80 mm Hg (diastolic pressure), which
cles contract when the ventricular walls contract but, is two thirds the maximal pressure of 120 mm Hg (sys-
contrary to what might be expected, they do not help the tolic pressure) that occurs in the aorta during ventricular
valves to close. Instead, they pull the vanes of the valves contraction.
inward toward the ventricles to prevent their bulging too The pressure curves in the right ventricle and pulmo-
far backward toward the atria during ventricular contrac- nary artery are similar to those in the aorta, except that
tion. If a chorda tendina becomes ruptured, or if one of the pressures are only about one-sixth as great, as dis-
the papillary muscles becomes paralyzed due to low blood cussed in Chapter 14.
  
120
 Chapter 9 Cardiac Muscle: The Heart as a Pump and Function of the Heart Valves

Relationship of the Heart Sounds to Heart Pumping 300

Left intraventricular pressure (mm Hg)

Systolic pressure
When listening to the heart with a stethoscope, one does not
hear the opening of the valves because this is a relatively slow 250
process that normally makes no noise. However, when the
200 Isovolumic
valves close, the vanes of the valves and the surrounding fluids relaxation

UNIT III
vibrate under the influence of sudden pressure changes, giving
Period of ejection
off sound that travels in all directions through the chest. 150
When the ventricles contract, one first hears a sound
III Isovolumic
caused by closure of the A-­V valves. The vibration pitch is 100 contraction
low and relatively long-­lasting and is known as the first heart EW
sound (S1). When the aortic and pulmonary valves close at 50 IV
II Diastolic
the end of systole, one hears a rapid snap because these valves PE pressure
I
close rapidly, and the surroundings vibrate for a short period. 0
This sound is called the second heart sound (S2). The precise 0 50 100 150 200 250
causes of the heart sounds are discussed more fully in Chapter Period of filling Left ventricular volume (ml)
23 in relation to listening to the sounds with the stethoscope.
Figure 9-­10. Relationship between left ventricular volume and intra-
Work Output of the Heart ventricular pressure during diastole and systole. Also shown by the
red lines is the “volume-­pressure diagram,” demonstrating changes
The stroke work output of the heart is the amount of energy in intraventricular volume and pressure during the normal cardiac cy-
that the heart converts to work during each heartbeat while cle. EW, Net external work; PE, potential energy.
pumping blood into the arteries. Work output of the heart
is in two forms. First, the major proportion is used to move
Until the volume of the noncontracting ventricle
the blood from the low-­pressure veins to the high-­pressure
arteries. This is called volume-­pressure work or external
rises above about 150 ml, the diastolic pressure does
work. Second, a minor proportion of the energy is used to not increase much. Therefore, up to this volume, blood
accelerate the blood to its velocity of ejection through the can flow easily into the ventricle from the atrium. Above
aortic and pulmonary valves, which is the kinetic energy of 150 ml, the ventricular diastolic pressure increases rap-
blood flow component of the work output. idly, partly because of fibrous tissue in the heart that will
Right ventricular external work output is normally stretch no more, and partly because the pericardium that
about one-sixth the work output of the left ventricle be- surrounds the heart becomes filled nearly to its limit.
cause of the sixfold difference in systolic pressures pumped During ventricular contraction, the systolic pressure
by the two ventricles. The additional work output of each increases, even at low ventricular volumes, and reaches a
ventricle required to create kinetic energy of blood flow is maximum at a ventricular volume of 150 to 170 ml. Then,
proportional to the mass of blood ejected times the square
as the volume increases further, the systolic pressure actu-
of velocity of ejection.
Ordinarily, the work output of the left ventricle required
ally decreases under some conditions, as demonstrated
to create kinetic energy of blood flow is only about 1% of by the falling systolic pressure curve in Figure 9-­10. This
the total work output of the ventricle and therefore is ig- occurs because at these great volumes, the actin and myo-
nored in the calculation of the total stroke work output. In sin filaments of the cardiac muscle fibers are pulled apart
certain abnormal conditions, however, such as aortic ste- far enough that the strength of each cardiac fiber contrac-
nosis, in which blood flows with great velocity through the tion becomes less than optimal.
stenosed valve, more than 50% of the total work output may Note especially in the figure that the maximum sys-
be required to create kinetic energy of blood flow. tolic pressure for the normal left ventricle is between 250
and 300 mm Hg, but this varies widely with each person’s
heart strength and degree of heart stimulation by cardiac
GRAPHIC ANALYSIS OF VENTRICULAR nerves. For the normal right ventricle, the maximum sys-
PUMPING tolic pressure is between 60 and 80 mm Hg.
Figure 9-­10 shows a diagram that is especially useful in
explaining the pumping mechanics of the left ventricle. Volume-­Pressure Diagram During the Cardiac Cycle;
The most important components of the diagram are the Cardiac Work Output. The red lines in Figure 9-­10 form
two curves labeled “diastolic pressure” and “systolic pres- a loop called the volume-­pressure diagram of the cardiac
sure.” These curves are volume-­pressure curves. cycle for normal function of the left ventricle. A more de-
The diastolic pressure curve is determined by filling tailed version of this loop is shown in Figure 9-­11. It is
the heart with progressively greater volumes of blood and divided into four phases.
then measuring the diastolic pressure immediately before Phase I: Period of Filling. Phase I in the volume-­
ventricular contraction occurs, which is the end-­diastolic pressure diagram begins at a ventricular volume of about
pressure of the ventricle. 50 ml and a diastolic pressure of 2 to 3 mm Hg. The
The systolic pressure curve is determined by recording amount of blood that remains in the ventricle after the
the systolic pressure achieved during ventricular contrac- previous heartbeat, 50 ml, is called the end-­systolic vol-
tion at each volume of filling. ume. As venous blood flows into the ventricle from the

121
UNIT III The Heart

Period of ejection
120

Aortic valve
100 closes
D

Left intraventricular pressure (mm Hg)

EW
Aortic valve
80 opens
C
Isovolumetric
relaxation
60
Stroke volume Isovolumetric
contraction

40

20 End-systolic End-diastolic
Figure 9-­11. The volume-­pressure diagram dem- volume Period of volume B
onstrating changes in intraventricular volume and Mitral valve filling Mitral valve
opens A
pressure during a single cardiac cycle (red line). closes
The shaded area represents the net external work 0
(EW) output by the left ventricle during the cardiac 0 50 70 90 110 130
cycle. Left ventricular volume (ml)

left atrium, the ventricular volume normally increases to contraction, this diagram is used for calculating cardiac
about 120 ml, called the end-­diastolic volume, an increase work output.
of 70 ml. Therefore, the volume-­pressure diagram during When the heart pumps large quantities of blood, the
phase I extends along the line in Figure 9-­10 labeled “I” area of the work diagram becomes much larger. That is,
and from point A to point B in Figure 9-­11, with the vol- it extends far to the right because the ventricle fills with
ume increasing to 120 ml and the diastolic pressure rising more blood during diastole, it rises much higher because
to about 5 to 7 mm Hg. the ventricle contracts with greater pressure, and it usu-
Phase II: Period of Isovolumic Contraction. During ally extends farther to the left because the ventricle con-
isovolumic contraction, the volume of the ventricle does tracts to a smaller volume—especially if the ventricle is
not change because all valves are closed. However, the stimulated to increased activity by the sympathetic ner-
pressure inside the ventricle increases to equal the pres- vous system.
sure in the aorta, at a pressure value of about 80 mm Hg,
as depicted by point C (see Figure 9-­11). Concepts of Preload and Afterload. In assessing the
Phase III: Period of Ejection. During ejection, the contractile properties of muscle, it is important to specify
systolic pressure rises even higher because of still more the degree of tension on the muscle when it begins to con-
contraction of the ventricle. At the same time, the volume tract, called the preload, and to specify the load against
of the ventricle decreases because the aortic valve has which the muscle exerts its contractile force, called the
now opened, and blood flows out of the ventricle into the afterload.
aorta. Therefore, in Figure 9-­10, the curve labeled “III,” For cardiac contraction, the preload is usually con-
or “period of ejection,” traces the changes in volume and sidered to be the end-­diastolic pressure when the ven-
systolic pressure during this period of ejection. tricle has become filled. The afterload of the ventricle
Phase IV: Period of Isovolumic Relaxation. At the end is the pressure in the aorta leading from the ventricle.
of the period of ejection (point D, Figure 9-­11), the aortic In Figure 9-­10, this corresponds to the systolic pressure
valve closes, and the ventricular pressure falls back to the described by the phase III curve of the volume-­pressure
diastolic pressure level. The line labeled “IV” (Figure 9-­ diagram. (Sometimes the afterload is loosely considered
10) traces this decrease in intraventricular pressure with- to be the resistance in the circulation rather than the
out any change in volume. Thus, the ventricle returns to pressure.)
its starting point, with about 50 ml of blood left in the The importance of the concepts of preload and after-
ventricle at an atrial pressure of 2 to 3 mm Hg. load is that in many abnormal functional states of the
The area subtended by this functional volume-­ heart or circulation, the pressure during filling of the ven-
pressure diagram (the shaded area, labeled “EW”) repre- tricle (the preload), the arterial pressure against which the
sents the net external work output of the ventricle during ventricle must contract (the afterload), or both are altered
its contraction cycle. In experimental studies of cardiac from normal to a severe degree.
  
122
 Chapter 9 Cardiac Muscle: The Heart as a Pump and Function of the Heart Valves

Chemical Energy Required for Cardiac Contraction: (2) control of heart rate and heart strength by the auto-
Oxygen Utilization by the Heart nomic nervous system.
Heart muscle, like skeletal muscle, uses chemical energy
to provide the work of contraction. Approximately 70%
to 90% of this energy is normally derived from oxidative
INTRINSIC REGULATION OF HEART
PUMPING—THE FRANK-­STARLING

UNIT III
metabolism of fatty acids, with about 10% to 30% com-
ing from other nutrients, especially glucose and lactate. MECHANISM
Therefore, the rate of oxygen consumption by the heart In Chapter 20, we will learn that under most conditions,
is an excellent measure of the chemical energy liberated
the amount of blood pumped by the heart each minute is
while the heart performs its work. The different chemi-
normally determined almost entirely by the rate of blood
cal reactions that liberate this energy are discussed in
Chapters 68 and 69. flow into the heart from the veins, which is called venous
Experimental studies have shown that oxygen consump- return. That is, each peripheral tissue of the body controls
tion of the heart and the chemical energy expended during its own local blood flow, and all the local tissue flows com-
contraction are directly related to the total shaded area in bine and return by way of the veins to the right atrium.
Figure 9-­10. This shaded portion consists of the external The heart, in turn, automatically pumps this incoming
work (EW), as explained earlier, and an additional portion blood into the arteries so that it can flow around the cir-
called the potential energy, labeled “PE.” The potential ener- cuit again.
gy represents additional work that could be accomplished by This intrinsic ability of the heart to adapt to increasing
contraction of the ventricle if the ventricle could completely volumes of inflowing blood is called the Frank-­Starling
empty all the blood in its chamber with each contraction.
mechanism of the heart, named in honor of Otto Frank
Oxygen consumption has also been shown to be nearly
and Ernest Starling, two great physiologists. Basically, the
proportional to the tension that occurs in the heart mus-
cle during contraction multiplied by the duration of time Frank-­Starling mechanism means that the more the heart
that the contraction persists; this is called the tension-­time muscle is stretched during filling, the greater is the force
index. According to the law of Laplace, ventricular wall ten- of contraction, and the greater is the quantity of blood
sion (T) is related to the left ventricular pressure (P) and the pumped into the aorta. Or, stated another way—within
radius (r): T = P × r. physiological limits, the heart pumps all the blood that
Because tension is high when systolic pressure (and returns to it by way of the veins.
therefore left ventricular pressure) is high, correspondingly
more oxygen is used. When systolic pressure is chroni- What Is the Explanation of the Frank-­Starling Mech-
cally elevated, wall stress and cardiac workload are also in- anism? When an extra amount of blood flows into the
creased, inducing thickening of the left ventricular walls,
ventricles, the cardiac muscle is stretched to a greater
which can reduce the ventricular chamber radius (concen-
length. This stretching causes the muscle to contract with
tric hypertrophy) and at least partially relieve the increased
wall tension. Also, much more chemical energy is expend- increased force because the actin and myosin filaments
ed, even at normal systolic pressures, when the ventricle are brought to a more nearly optimal degree of overlap
is abnormally dilated (eccentric hypertrophy) because the for force generation. Therefore, the ventricle, because of
heart muscle tension during contraction is proportional to its increased pumping, automatically pumps the extra
pressure times the radius of the ventricle. This becomes es- blood into the arteries. This ability of stretched muscle,
pecially important in heart failure when the heart ventricle up to an optimal length, to contract with increased work
is dilated and, paradoxically, the amount of chemical en- output is characteristic of all striated muscle, as explained
ergy required for a given amount of work output is greater in Chapter 6, and is not simply a characteristic of cardiac
than normal, even though the heart is already failing. muscle.
Cardiac Efficiency. During heart muscle contraction, In addition to the important effect of lengthening the
most of the expended chemical energy is converted into heat,
heart muscle, another factor increases heart pumping
and a much smaller portion is converted into work output.
when its volume is increased. Stretch of the right atrial
Cardiac efficiency is the ratio of work output to total chemi-
cal energy used to perform the work. Maximum efficiency of wall directly increases the heart rate by 10% to 20%, which
the normal heart is between 20% and 25%. In persons with also helps increase the amount of blood pumped each
heart failure, this efficiency can decrease to as low as 5%. minute, although its contribution is much less than that
of the Frank-­Starling mechanism. As discussed in Chapter
18, stretch of the atrium also activates stretch receptors
and a nervous reflex, the Bainbridge reflex, that is trans-
REGULATION OF HEART PUMPING
mitted by the vagus nerve and may increase heart rate an
When a person is at rest, the heart pumps only 4 to 6 additional 40% to 60%.
liters of blood each minute. During strenuous exercise,
the heart may pump four to seven times this amount. The Ventricular Function Curves
basic mechanisms for regulating heart pumping are as fol- One of the best ways to express the functional ability of
lows: (1) intrinsic cardiac pumping regulation in response the ventricles to pump blood is by ventricular function
to changes in volume of blood flowing into the heart; and curves. Figure 9-­12 shows a type of ventricular function

123
UNIT III The Heart

Left ventricular Right ventricular Vagi

stroke work stroke work
(gram-meters) (gram-meters)
40 4
30 3
Sympathetic
20 2 chain
10 1 S-A
node A-V
0 0 node
0 10 20 0 10 20
Left mean atrial Right mean atrial
pressure pressure
(mm Hg) (mm Hg)
Figure 9-­12. Left and right ventricular function curves recorded from
dogs, depicting ventricular stroke work output as a function of left
and right mean atrial pressures. (Data from Sarnoff SJ: Myocardial
contractility as described by ventricular function curves. Physiol Rev
35:107, 1955.)

Sympathetic nerves
15
Ventricular output (L/min)

Right ventricle Figure 9-­14. Cardiac sympathetic and parasympathetic nerves. (The
vagus nerves to the heart are parasympathetic nerves.) A-­V, Atrioven-
10 tricular; S-­A, sinoatrial.
Left ventricle

increased more than 100% by sympathetic stimulation. By

5 contrast, the output can be decreased to almost zero by
vagal (parasympathetic) stimulation.
0
–4 0 +4 +8 +12 +16
Mechanisms of Excitation of the Heart by the Sym-
Atrial pressure (mm Hg) pathetic Nerves. Strong sympathetic stimulation can
increase the heart rate in young adult humans from the
Figure 9-­13. Approximate normal right and left ventricular volume
output curves for the normal resting human heart as extrapolated normal rate of 70 beats/min up to 180 to 200 beats/min
from data obtained in dogs and data from humans. and, rarely, even 250 beats/min. Also, sympathetic stimu-
lation may double the force of heart contraction, thereby
curve called the stroke work output curve. Note that as increasing the volume of blood pumped and increasing the
atrial pressure for each side of the heart increases, stroke ejection pressure. Thus, sympathetic stimulation often can
work output for that side increases until it reaches the increase the maximum cardiac output as much as twofold
limit of the ventricle’s pumping ability. to threefold, in addition to the increased output caused by
Figure 9-­13 shows another type of ventricular func- the Frank-­Starling mechanism already discussed.
tion curve called the ventricular volume output curve. The Conversely, inhibition of the sympathetic nerves to the
two curves of this figure represent function of the two heart can decrease cardiac pumping to a moderate extent.
ventricles of the human heart based on data extrapolated Under normal conditions, the sympathetic nerve fibers
from experimental animal studies. As the right and left to the heart discharge continuously at a slow rate that
atrial pressures increase, the respective ventricular vol- maintains pumping at about 30% above that with no sym-
ume outputs per minute also increase. pathetic stimulation. Therefore, when sympathetic ner-
Thus, ventricular function curves are another way of vous system activity is depressed below normal, both the
expressing the Frank-­Starling mechanism of the heart. heart rate and strength of ventricular muscle contraction
That is, as the ventricles fill in response to higher atrial decrease, thereby decreasing the level of cardiac pumping
pressures, each ventricular volume and strength of car- by as much as 30% below normal.
diac muscle contraction increase, causing the heart to
pump increased quantities of blood into the arteries. Parasympathetic (Vagal) Stimulation Reduces Heart
Rate and Strength of Contraction. Strong stimulation
Control of the Heart by the Sympathetic of the parasympathetic nerve fibers in the vagus nerves
and Parasympathetic Nerves to the heart can stop the heartbeat for a few seconds, but
The pumping effectiveness of the heart also is controlled then the heart usually “escapes” and beats at a rate of 20
by the sympathetic and parasympathetic (vagus) nerves, to 40 beats/min as long as the parasympathetic stimula-
which abundantly supply the heart, as shown in Figure tion continues. In addition, strong vagal stimulation can
9-­14. For given levels of atrial pressure, the amount of decrease the strength of heart muscle contraction by 20%
blood pumped each minute (cardiac output) often can be to 30%.

124
 Chapter 9 Cardiac Muscle: The Heart as a Pump and Function of the Heart Valves

25
Maximum sympathetic ions in the extracellular fluids have important effects on
stimulation cardiac pumping.

Effect of Potassium Ions. Excess potassium in the ex-

20
tracellular fluids causes the heart to become dilated and

UNIT III
flaccid and also slows the heart rate. Large quantities of
Cardiac output (L/min)

Normal sympathetic potassium also can block conduction of the cardiac im-
15
stimulation pulse from the atria to the ventricles through the A-­V
bundle. Elevation of potassium concentration to only 8
Zero sympathetic
to 12 mEq/L—two to three times the normal value—can
10 stimulation cause severe weakness of the heart, abnormal rhythm,
(Parasympathetic and death.
stimulation) These effects result partially from the fact that a
5
high potassium concentration in the extracellular fluids
decreases the resting membrane potential in the car-
diac muscle fibers, as explained in Chapter 5. That is, a
0
–4 0 +4 +8
high extracellular fluid potassium concentration partially
Right atrial pressure (mm Hg)
depolarizes the cell membrane, causing the membrane
potential to be less negative. As the membrane poten-
Figure 9-­15. Effect on the cardiac output curve of different degrees
of sympathetic or parasympathetic stimulation.
tial decreases, the intensity of the action potential also
decreases, which makes contraction of the heart progres-
sively weaker.
The vagal fibers are distributed mainly to the atria and
not much to the ventricles, where the power contrac- Effect of Calcium Ions. Excess calcium ions cause effects
tion of the heart occurs. This distribution explains why almost exactly opposite to those of potassium ions, caus-
the effect of vagal stimulation is mainly to decrease the ing the heart to move toward spastic contraction. This ef-
heart rate rather than to decrease greatly the strength fect is caused by a direct effect of calcium ions to initiate
of heart contraction. Nevertheless, the great decrease in the cardiac contractile process, as explained earlier in this
heart rate, combined with a slight decrease in heart con- chapter.
traction strength, can decrease ventricular pumping by Conversely, deficiency of calcium ions causes cardiac
50% or more. weakness, similar to the effect of high potassium. For-
tunately, calcium ion levels in the blood normally are
Effect of Sympathetic or Parasympathetic Stimula- regulated within a very narrow range. Therefore, cardiac
tion on the Cardiac Function Curve. Figure 9-­15 shows effects of abnormal calcium concentrations are seldom of
four cardiac function curves. These curves are similar to clinical concern.
the ventricular function curves of Figure 9-­13. However,
they represent function of the entire heart rather than
EFFECT OF TEMPERATURE ON HEART
that of a single ventricle. They show the relationship be-
FUNCTION
tween right atrial pressure at the input of the right heart
and cardiac output from the left ventricle into the aorta. Increased body temperature, such as that which occurs
The curves of Figure 9-­15 demonstrate that at any during fever, greatly increases the heart rate, sometimes
given right atrial pressure, the cardiac output increases to double the normal rate. Decreased temperature greatly
during increased sympathetic stimulation and decreases decreases the heart rate, which may fall to as low as a
during increased parasympathetic stimulation. These few beats per minute when a person is near death from
changes in output caused by autonomic nervous system hypothermia in the body temperature range of 60° to 70°F
stimulation result from changes in heart rate and from (15.5°–21°C). These effects presumably result from the
changes in contractile strength of the heart. fact that heat increases the permeability of the cardiac
muscle membrane to ions that control heart rate, result-
ing in acceleration of the self-­excitation process.
EFFECT OF POTASSIUM AND CALCIUM
Contractile strength of the heart often is enhanced
IONS ON HEART FUNCTION
temporarily by a moderate increase in temperature, such
In our discussion of membrane potentials in Chapter 5, as that which occurs during body exercise, but prolonged
we pointed out that potassium ions have a marked effect temperature elevation exhausts the metabolic systems of
on membrane potentials, and in Chapter 6 we noted that the heart and eventually causes weakness. Therefore, opti-
calcium ions play an especially important role in activat- mal heart function depends greatly on proper control of
ing the muscle contractile process. Therefore, it is not body temperature by the control mechanisms explained
surprising that the concentrations of each of these two in Chapter 74.

125
UNIT III The Heart

Normal range Dewenter M, von der Lieth A, Katus HA, Backs J: Calcium signal-
ing and transcriptional regulation in cardiomyocytes. Circ Res
Cardiac output (L/min) 5 121:1000, 2017.
Doenst T, Nguyen TD, Abel ED: Cardiac metabolism in heart failure:
4 implications beyond ATP production. Circ Res 113:709, 2013.
Eisner DA, Caldwell JL, Kistamás K, Trafford AW: Calcium and
3
excitation-­contraction coupling in the heart. Circ Res 121:181,
2 2017.
Finkel T, Menazza S, Holmström KM, et al: The ins and outs of mito-
1 chondrial calcium. Circ Res 116:1810, 2015.
Guyton AC, Jones CE, Coleman TG: Circulatory Physiology: Cardiac
0
0 50 100 150 200 250 Output and Its Regulation, 2nd ed. Philadelphia: WB Saunders,
1973.
Arterial pressure (mm Hg)
Kho C, Lee A, Hajjar RJ: Altered sarcoplasmic reticulum calcium cy-
Figure 9-­16. Constancy of cardiac output up to a pressure level of cling—targets for heart failure therapy. Nat Rev Cardiol 9:717, 2012.
160 mm Hg. Only when the arterial pressure rises above this normal Lewis GA, Schelbert EB, Williams SG, et al: Biological phenotypes of
limit does the increasing pressure load cause the cardiac output to heart failure with preserved ejection fraction. J Am Coll Cardiol
fall significantly. 70:2186, 2017.
Luo M, Anderson ME: Mechanisms of altered Ca2+ handling in heart
failure. Circ Res 113:690, 2013.
INCREASING THE ARTERIAL PRESSURE Mangoni ME, Nargeot J: Genesis and regulation of the heart automa-
LOAD (UP TO A LIMIT) DOES NOT ticity. Physiol Rev 88:919, 2008.
DECREASE CARDIAC OUTPUT Marks AR: Calcium cycling proteins and heart failure: mechanisms
and therapeutics. J Clin Invest 123:46, 2013.
Note in Figure 9-­16 that increasing the arterial pressure Mayourian J, Ceholski DK, Gonzalez DM, et al: Physiologic, patho-
in the aorta does not decrease cardiac output until the logic, and therapeutic paracrine modulation of cardiac excitation-­
contraction coupling. Circ Res 122:167, 2018.
mean arterial pressure rises above about 160 mm Hg. In Omar AM, Vallabhajosyula S, Sengupta PP: Left ventricular twist and
other words, during normal heart function at normal sys- torsion: research observations and clinical applications. Circ Car-
tolic arterial pressures (80–140 mm Hg), cardiac output diovasc Imaging 8:74, 2015.
is determined almost entirely by the ease of blood flow Puglisi JL, Negroni JA, Chen-­Izu Y, Bers DM: The force-­frequency re-
through the body’s tissues, which in turn controls venous lationship: insights from mathematical modeling. Adv Physiol Educ
37:28, 2013.
return of blood to the heart. This mechanism is the prin- Sarnoff SJ: Myocardial contractility as described by ventricular func-
cipal subject of Chapter 20. tion curves. Physiol Rev 35:107, 1955.
Starling EH: The Linacre Lecture on the Law of the Heart. London:
Longmans Green, 1918.
Bibliography ter Keurs HE: The interaction of Ca2+ with sarcomeric proteins: role
Bell V, Mitchell GF: Influence of vascular function and pulsatile hemo- in function and dysfunction of the heart. Am J Physiol Heart Circ
dynamics on cardiac function. Curr Hypertens Rep 17: 580, 2015. Physiol 302:H38, 2012.
Bertero E, Maack C: Calcium signaling and reactive oxygen species in Triposkiadis F, Pieske B, Butler J, et al: Global left atrial failure in heart
mitochondria. Circ Res 122: 1460, 2018 failure. Eur J Heart Fail 18:1307, 2016.
Cingolani HE, Pérez NG, Cingolani OH, Ennis IL: The Anrep effect: Vega RB, Kelly DP: Cardiac nuclear receptors: architects of mitochon-
100 years later. Am J Physiol Heart Circ Physiol 304:H175, 2013. drial structure and function. J Clin Invest 127:1155, 2017.

126