NROSCI/BIOSC 1070 and MSNBIO 2070
September 21 & 23, 2015
Cardiovascular 3 & 4: Mechanical Actions of the Heart and Determinants
of Cardiac Output
An essential component for the operation of the heart is the action of the valves. The valves insure that
blood moves in only one direction. The opening and closing of the heart valves is controlled simply
by the pressure gradients on the two sides of the valves.
The two arteriovenous (AV) valves, the tricuspid and mitral
valves, are comprised of flaps of connective tissue. On the
ventricular side, the valves are attached to collagen cords
called the cordae tendinae. The opposite ends of the cords
are attached to the moundlike extensions of ventricular muscle
called papillary muscles. The cordae tendinae prevent the
flaps of the valve from getting stuck against the ventricular wall
during ventricular filling and from being forced into the atria
during ventricular systole. In contrast, the aortic and pulmonary
semilunar valves have three cuplike leaflets that fill with blood,
and which snap closed when backward pressure is placed on
them. Special tethering such as the chordae tendinae are not
required to insure that the semilunar valves close properly.
The closing of the heart valves generates vibrations, which result in the heart sounds that physicians
often monitor during examinations. The major heart sounds are commonly referred to as “lub-dub”.
The softer “lub” is associated with closing of the tricuspid and mitral valves, and the “dub” comes from
the closing of the semilunar valves.
Careful assessment of the heart sounds can be done using a stethoscope; the procedure is referred
to a auscultation. Through careful monitoring, two additional heart sounds are revealed. The third
heart sound is associated with turbulent blood flow into the ventricle near the beginning of ventricular
filling, and the fourth heart sound is produced by additional turbulent flow into the ventricle during
atrial contraction.
The heart sounds become abnormal if the valves are diseased. Two general types of abnormal heart
sounds can be classified: a murmur and a gallop. Murmurs are heart sounds in addition to the four
that are normally present, and gallops are augmented third or fourth heart sounds. Murmurs often
occur when valves fail to close properly, producing regurgitation or movement of blood in the wrong
direction. For example, if an AV valve does not close properly, blood will move from the ventricle into
the atrium during systole. This turbulent movement of blood can be heard as an additional heart sound.
Gallops often occur when the AV valves do not open properly or are narrowed (stenosed), resulting
in excessive turbulence during movement of blood from the atria into the ventricles. Gallops can also
occur when the ventricles are very stiff.
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Clinical Notes: Echocardiography
The beating heart can be imaged in real time using echocardiography. This technique employs ultrasound that is emitted from a piezoelectric crystal. The waves are reflected back to the crystal, and result in the production of electric impulses that are recorded. The characteristics of the reflected waves
are dependent on the properties of the tissue that the waves pass through. A computer can interpret the
electrical impulses generated by the vibrating pizoelectric crystal, and construct an image from these
signals.
There are three general placements for the echocardiograph transducer:
•
•
•
Transthoracic echocardiogram (TTE), in which a transducer is moved over different locations on the chest or abdomen.
Transesophageal echocardiogram (TEE), in which the transducer is passed down
the esophagus to provide clearer pictures of the heart.
Intracardiac echocardiogram, in which the transducer is inserted into the cardiac
vessels.
The following diagram shows two common planes imaged using transthoracic echocardiography:
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Another way of describing the cardiac cycle is through a pressure-volume graph. Between points A and B
in this graph, the ventricles are filling with blood.
The AV valves open when the pressure in the atria
exceeds that in the ventricles. After the AV valves
open, ventricular pressure increases slightly as volume increases. At the end of this part of the cardiac
cycle, the atria contract and the ventricles contain the
maximal amount of blood that they will have during
the cardiac cycle (end diastolic volume, shown at
point B). Note that although end diastolic volume is
typically about 135 ml, it can be more or less under
certain conditions. For example, when heart rate
is very high (and filling time is low), end diastolic
volume often drops. When cardiac return increases,
EDV also increases.
In the next phase of the cardiac cycle, the ventricles begin to contract. Very rapidly, pressure in the
ventricles exceeds that in the atria and the AV valves close. Subsequently, ventricular pressure increases
but ventricular volume stays constant (hence, an isovolumetric contraction). When pressure in the
ventricles is great enough, the semilunar valves open and blood is ejected into the aorta and pulmonary
arteries (point C). Ventricular pressure continues to increase while ventricular volume drops. Eventually,
the ventricles begin to relax, and the semilunar valves close. Note that ventricular volume is not zero
at this time, but instead end-systolic volume is about 65 ml. This volume is variable, however, and can
decrease if ventricular contractility increases. The ventricle then relaxes, but because the ventricular
pressure exceeds atrial pressure the AV valves are closed. This is the isovolumetric relaxation phase
of the cardiac cycle. When ventricular pressure drops below atrial pressure, the AV valves open and
ventricular filling starts again.
Note that if MAP increases, more pressure is needed in the left ventricle to open the aortic valve.
Ejection fraction (EF) is defined as the fraction of end diastolic volume that is ejected out of the
ventricle during each contraction.
EF = SV/EDV If SV=70ml and EDV=135ml Then EF=70/135 or 0.52
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Yet another means of depicting the cardiac cycle is shown above. This diagram includes both electrical
and mechanical events that occur in the heart. Such a diagram is called the “Wiggers diagram” after
the physiologist who first published it (Carl Wiggers).
We have not discussed one pressure tracing in the Wigger’s diagram: a recording of pressure in the left
atrium. Three waves are evident: the a, c, and v waves. The a wave is caused by atrial contraction.
The c wave is caused by ventricular contraction, and is due to 1) the small backflow of blood from
the ventricle to the atrium when the mitral valve closes and 2) the bulging of the closed mitral valve
backward into the atrium when ventricle pressure increases. The v wave is due to blood flowing from
the veins into the atrium during ventricular contraction, which cannot leave because the mitral valve is
shut. When the mitral valve opens, atrial pressure drops, demarking the peak of the v wave.
It is important for you to understand the relationships between MAP, aortic valve opening, and end
systolic volume. If total peripheral resistance increases, then the pressure in the left ventricle must
increase more to open the aortic valve (since MAP is higher [MAP=CO*TPR], and the pressure in the
left ventricle must exceed that in the aorta for the valve to open). In addition, the valve closes earlier
when the ventricle begins to relax. As a consequence, stroke volume diminishes.
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When stroke volume diminishes, there is more blood left in the ventricle at the end of systole (end
systolic volume increases). This increased volume is added to the volume transferred from the left
atrium to left ventricle after the mitral valve opens. As a consequence, end diastolic volume increases.
Thus, the next ventricular contraction is stronger due to the Frank-Starling effect.
In essence, if TPR is high, then the heart must work harder and use more ATP to maintain constant
cardiac output.
Cardiac output is the amount of blood pumped from the ventricles per unit time. As mentioned in
the first lecture, cardiac output at rest is about 5 L/min. This value is derived through the following
calculation. The resting heart beats at about 70 times/min, and each ventricular ejection is about 70 ml
(EDV-ESV). Thus, 70 beats/min * 0.07 L/beat = 4.9 L/min. You should be familiar with the formula
to compute cardiac output, and how cardiac output relates to mean arterial pressure.
MAP = CO * TPR
MAP=(SV*HR) * TPR
SV= Stroke Volume
HR=Heart Rate
MAP=((EDV-ESV)*HR) * TPR
Cardiac output can be changed tremendously during some conditions. For example, during exercise it
can rise from 5 L/min to 35 L/min. Let us consider how this happens. Obviously, an increase in stroke
volume or heart rate can increase cardiac output. During the last lecture, we noted that intrinsic heart rate
is actually 90-100 beats/min, but is tonically suppressed to about 70 beats/minute by the parasympathetic
nervous system. Thus, one way of increasing heart rate is by “withdrawing” parasympathetic drive on
the heart. Heart rate can be increased further by the actions of the sympathetic nervous system. Recall
that binding of NE or EPI to beta receptors on autorhythmic cells increases their firing rate, driving
heart rate faster. Furthermore, the catecholamines enhance conduction through the AV node, bundle
of His, and Purkinje fibers.
However, there is an upward limit on heart rate. If the heart beats too rapidly, there is insufficient time
for filling. This condition is called tachycardia. This begins to happen when heart rate exceeds ~170
beats/min. A limit on heart rate is imposed by the delay in conduction through the AV node as well as
the long refractory period of myocardial cells. This limitation helps to insure that the heart will not beat
too rapidly to effectively pump out blood. However, under certain pathological conditions tachycardia
becomes so severe that circulatory collapse occurs.
So, an increase in heart rate alone cannot explain the seven-fold increase in cardiac output that can occur
during exercise. Stroke volume must also increase in order to amplify cardiac output. As noted in the last
lecture, binding of catecholamines to beta-receptors on myocardial cells increases how powerfully they
will contract. In other words, the sympathetic nervous system acts to enhance contractility. Obviously,
increasing contractility tends to reduce end systolic volume, thereby increasing stroke volume. Any
agent that increases cardiac contractility is called an inotropic agent.
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Another way of enhancing stroke volume is to increase venous return (thereby increasing end
diastolic volume). As noted previously, under physiological conditions the heart will pump
out as much blood as it receives (the Frank-Starling Law of the Heart). This enhanced
cardiac output during increased cardiac return is due to the fact that myocardial cells are
stretched, which places their actin and myosin into a more efficient arrangement for contraction.
In addition to mechanically affecting contraction strength by altering the relationship between the
contractile proteins actin and myosin in cardiac muscle cells, stretch of a ventricle affects the sensitivity
of the calcium-binding protein troponin for calcium. This heightened sensitivity increases the rate of
cross-bridge attachment and detachment, and the amount of tension developed by the muscle fiber .
These two adaptations result in a more intense ventricular contraction when the chamber’s filling with
blood increases. Thus, an increase in end diastolic volume insures that cardiac output will also increase.
There are important limitations to consider in the relationships diagrammed above. When heart rate
increases, there is a decrease in filling time for the ventricles, which tends to decrease stroke volume
(Frank-Starling effect). However, this is offset by the Bowditch effect if increases in heart rate are only
moderate. At heart rates > 140 bpm, filling time is so limited that cardiac output declines precipitously.
There are also limits to ventricular filling. When the ventricle is full, pressure increases as more blood
enters the ventricle. The pressure in the ventricle soon is equal to atrial pressure, such that there is no
driving force for blood to enter the ventricle.
The Notions of Preload and Afterload
Preload is the pressure stretching the ventricle of the heart, after passive filling of the ventricle and
subsequent atrial contraction. All the factors that increase venous return will also serve to increase
preload. As noted previously, preload is a major factor that augments cardiac output, via the FrankStarling mechanism.
Afterload is the mean tension produced by a chamber of the heart in order to eject blood. Another
way of looking at afterload is the force that must be overcome to eject blood from the ventricle.
A major factor contributing to afterload is aortic pressure: an increase in peripheral
resistance increases afterload.
As a consequence, the aortic valve closes earlier
during the cardiac cycle, cardiac output is reduced, and end systolic volume increases.
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However, other factors can also contribute to afterload. For example, aortic valve stenosis and an
increase in ventricular stiffness due to pathological changes in wall properties also increase afterload.
Note that increasing afterload produces a secondary increase in preload. The increased end systolic
volume is added to normal venous return. This increase in preload activates the Frank-Starling
mechanism to partially compensate for the reduction in stroke volume caused by the increase in
afterload.
The interaction between afterload and preload is utilized in the treatment following a heart attack, where
the left ventricle in damaged. Vasodilator drugs are used to augment stroke volume by decreasing
afterload, and at the same time, reduce ventricular preload. When arterial pressure is reduced, the
ventricle can eject blood more rapidly, which increases the stroke volume and thereby decreases the
end-systolic volume.
Because less blood remains in the ventricle after
systole, the ventricle will not fill to the same enddiastolic volume found before the afterload reduction. As a consequence, higher stroke volumes can
be sustained by weaker ventricular contractions, diminishing the risk of congestive heart failure.
Determinants of Cardiac Output
Cardiac output is influenced both by factors intrinsic to the heart (heart rate and
contractility) and factors extrinsic to the
heart (preload and afterload). If afterload
increases, then cardiac output drops unless
heart rate and contractility also increase. If
preload increases then cardiac output increases without any changes in heart rate
and contractility.
Hence Cardiac Output is dependent on the
interactions between the cardiac and vascular components.
Guyton and his colleagues conducted seminal experiments in the 1950s and 1960s to understand the
interactions between the heart and the vasculature, and how they influence cardiac output. These
interactions can be described through two equations that are plotted as the vascular function curve
(sometimes called the venous return curve) and cardiac function curve. These curves consider the
systemic circulation: a single pump and set of pipes.
The vascular function curve determines how systemic venous pressure (Pv), which is the same as right
atrial pressure, varies with changes in flow (Q) through the vasculature (or cardiac output). In other
words, the vascular function curve considers how pressure in the circulation is affected by the vasculature. In contrast, the cardiac function curve considers how changes in systemic venous pressure (Pv)
affects cardiac output.
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This analysis is undoubtedly artificial, since it discounts the effects of factors such as gravity and skeletal muscle pumping on the cardiovascular system. However, it does provide some important insights,
as noted below.
The analysis makes the following assumptions:
Q
(R)
Pv
Q
Cardiac Output = Venous Return
Central Venous Pressure = Right Atrial Pressure
Pa
Using the model to understand differences in arterial and venous pressures
As discussed in the first lecture, R = ΔP/Q (Ohm’s Law)
Thus, R=(Pa – Pv)/Q (ΔP must be the difference between arterial and venous pressures)
Assume that R = 20 mm Hg/L/min and Q = CO = 5 L/min
Then, 20 mm Hg/L/min = (Pa – Pv)/5 L/min
100 mm Hg = Pa – Pv
Pa = 100 mm Hg + Pv (in other words, Pa is 100 mm Hg greater than Pv).
Systemic Filling Pressure (Psf)
Normal
Heart Stopped
Q=5 L/min
Pv=2 mm Hg
Pa=102 mm Hg
Q=0 L/min
Pv=7 mm Hg
Pa=7 mm Hg
Guyton conducted experiments where the heart was transiently stopped in experimental animals. Immediately afterwards, pressures in the veins and arteries became equal. This pressure is known as
systemic filling pressure (Psf), which can be thought as the effective pressure head in the systemic
circulation pushing the blood back into the heart.
In mammals, Psf is approximately 7 mm Hg, which is much closer to normal venous pressure than to
normal arterial pressure. Why is this the case?
The answer relates to the fact that venous compliance is about 19 times higher than arterial compliance. The effects of vascular compliance on Psf can be determined quantitatively, as shown below.
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During the first lecture, we learned that: ΔP = ΔV/C or C = ΔV/ΔP
In the model:
Ca = ΔVa/ΔPa
Cv = ΔVv/ΔPv
We also know that: Cv=19Ca or Cv/Ca = 19
When the heart is stopped, blood volume moves between the arterial and venous compartments, and
the amount of blood moved is equal in the two compartments (the volume removed from one is placed
in the other): ΔVa = ΔVv
Hence:
CaΔPa = CvΔPv
CaΔPa = 19CaΔPv
ΔPa = 19ΔPv
In other words, the change in arterial pressure is much larger (19 times) than the change in venous
pressure. The resulting pressure must be much closer to the original arterial pressure.
For example, if the original Pa=102 mm Hg and the original Pv=2 mm Hg, then:
ΔPa = 102-X
ΔPv = X-2
(102-X) = 19(X-2)
(102-X)=19X-38
140-X=19X
140=20X
7=X = Psf
The Vascular Function or Venous Return Curve
The vascular function curve is derived based on the notion that the volumes of blood moving between
the arterial and venous compartments is equal: ΔVa = – ΔVv .
We have previously noted that: C = ΔV/ΔP so Ca = ΔVa/ΔPa and Cv = ΔVv/ΔPv
Applying algebra: Ca* ΔPa = ΔVa and Cv* ΔPv= ΔVv
Ca* ΔPa = – Cv* ΔPv
ΔPv/ΔPa = – Ca/Cv
We have also previously noted that: ΔPa = Pa – Psf and ΔPv = Pv – Psf
And Ohm’s law stipulates that: R = (Pa – Pv)/Q
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Using this information and applying algebra, the equations underlying the vascular function curve can
" R*C a %
! R*C v $
be derived:
Pv = Psf − $
Pa = Psf + #
'Q
&Q
# Ca + Cv &
" Ca + Cv %
This equation provides the relationship between:
Cardiac Factors
Pv, venous pressure (same as right atrial pressure)
Q, flow through the vascular system (same as venous return or cardiac output)
and Vascular Factors
R (peripheral resistance), Ca, Cv, and Psf.
The graphical depiction of this equation is called the vascular function curve or venous return curve.
This curve relates venous return (or cardiac
output) to right atrial pressure. As right atrial (venous) pressure increases, venous return
(or cardiac output) decreases and vice versa.
When right atrial pressure equals Psf, venous
return (or cardiac output) is zero, since there
is no pressure difference to drive blood flow.
Note that there is little additional venous return between a right atrial pressure of 0 mmHg and -8
mmHg (or any negative right atrial pressure). This is because the negative right atrial pressure tends
to suck together the walls of the large veins near the heart, which limits any further increase in blood
flow.
The major concept to learn from the vascular function curve is the following: Right atrial pressure
decreases as flow through the cardiovascular system (either venous return or cardiac output) increases.
This relationship is determined by vascular properties (R, Ca, Cv, and Psf).
Resistance to Vascular Return
Resistance to vascular return is essentially the resistance to movement of blood through the vasculature (essentially the same as total peripheral resistance, with the additional consideration of compliance of the vasculature). This value can be calculated using the model as follows:
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" R*Ca %
Pv = Psf − $
'Q
C
+
C
# a v&
so
and
! R*Ca $
RVR = #
&
" Ca + Cv %
so
" R*Ca %
Psf − Pv = $
'Q
C
+
C
# a v&
(Psf − Pv ) " R*Ca %
=$
'
Q
# Ca + Cv &
(Psf − Pv )
= RVR
Q
Note that vascular compliance has a major impact on retarding return of blood flow to the heart.
Note that the slope of the linear portion of the vascular function curve is 1/RVR.
Thus, for typical physiological values of Psf = 7 mm Hg, Pv = 2 mm Hg, and Q = 5 L/min:
(Psf − Pv )
= RVR
Q
(7 − 2 mmHg)
= 1 mmHg • min/L
5 L/min
The slope of the linear portion of the vascular function
curve is 1/RVR. Hence, as RVR increases, the slope
decreases.
This means that a given change in right atrial (venous)
pressure causes a smaller change in cardiac output (or
venous return) at higher RVR.
In addition, maximal cardiac output (or venous return)
is lower when RVR is high.
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The relative compliance of the venous and arterial vessels
has a major impact on relative pressures in the two types
of vessels, as illustrated in the graph to the left for different cardiac outputs.
As we have discussed,
CaΔPa = CvΔPv
Let us assume that Cv = 19Ca, so
CaΔPa = 19CaΔPv
ΔPa = 19ΔPv
At Q = 0, Pv = Pa = Psf = 7 mm Hg
At Q = 5 L/min, Pv = 2 mm Hg
thus
ΔPv = 5 mm Hg (= 7 – 2)
A small change in circulatory blood volume results in a
huge change in Psf, as reflected in the sharp steepness of
the curve relating the two parameters.
At a circulatory blood volume of 4 L, Psf is 0; this is the
unstressed volume, which is insufficient to contribute to
pressure because there is insufficient stretch of the vessel
walls. Any additional volume inside the cardiovascular
system above the unstressed volume is called the stressed
volume.
At a circulatory blood volume of 5 L, Psf = 7 mm Hg. If
blood volume increases by 10%, Psf doubles!
Changes in Psf produced by alterations in
circulatory volume have a huge impact
on cardiac output and venous return, as
illustrated in the graph to the left. An increase in Psf causes the vascular function
curve to shift upwards and to the right.
Consequently, at a particular right atrial
pressure, cardiac output and venous return are much larger.
In other words, when circulatory blood volume increases, it is much easier for the heart to fill with
blood, and cardiac output increases.
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Cardiac Function Curve
Now we will look at the effects of manipulating right atrial pressure on cardiac output. In essence, this
approach measures the effects of changing preload on cardiac output and blood pressure, and produces
the cardiac function curve.
In the experiments we will be discussing, cardiac contractile state and heart rate are maintained constant, as is arterial pressure (afterload).
The cardiac function curve is illustrated to the left. When right atrial
pressure is low, cardiac output is 0, since there is too little blood in
the cardiac chambers to generate pressure during systole. When
right atrial pressure increases above ~4 mm Hg, cardiac output is
maximum. This is because the ventricle fulls maximally, and thus
cannot accommodate more blood (the factors that limit ventricle
filling are discussed below).
The cardiac function curves to the left show the effect of increasing
heart rate on cardiac output. Modest increases in heart rate facilitate
cardiac output, despite a shorter ventricular filling time, due to the
Bowditch effect. However, large increases in heart rate shorten
filling time so much that cardiac output plummets.
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The cardiac output produced by a particular right atrial pressure is
altered if the ventricle is hypereffective or hypoeffective.
A hypereffective ventricle is present when sympathetic activity is
high, or the ventricle is hypertrophied (the muscle mass has increased due to factors such as chronic exercise). In addition, the
ventricle is hypereffective when afterload is low.
A hypoeffective ventricle is present when there is no sympathetic
stimulation, the ventricle is damaged, or afterload increases.
It is possible to plot the vascular function and cardiac function curves
on the same axes, as shown to the left. The two curves intersect
at one point, called the equilibrium point. This point indicates the
cardiac output, venous return, and right atrial pressure under this
particular physiological condition. In the adjacent graph, point A
shows the “normal” equilibrium point, when right atrial pressure is
near 0 and cardiac output and venous return are near 5 L/min. The
dashed line indicates the effect of increasing blood volume by 20%.
The vascular function curve shifts but the cardiac function curve
doesn’t. Note that Psf increases to about 16 mm Hg, right atrial
pressure is near 8 mm Hg, and cardiac output is ~13 L/min.
Under most conditions, both the cardiac output and vascular function curves shift during a manipulation.
For example, sympathetic nervous system activity causes the cardiac function curve to shift upwards
and a bit to the left, while the vascular function curve shifts upwards and to the right, as illustrated
below.
These effects are due to the following actions of the
sympathetic nervous system:
1) Increased cardiac contractility
2) Increased heart rate
3) Decreased venous compliance
4) Increased total peripheral resistance.
Note that afterload increases during sympathetic
stimulation, and this opposes a shift in the vascular function
curve. Consequently, cardiac output just rises to 10 L/min
during maximal sympathetic stimulation.
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During exercise, the shift in the venous return curve is considerably
different than during sympathetic stimulation. Why? First,
afterload decreases as arterioles in skeletal muscle dilate (the
mechanisms involved will be discussed in subsequent lectures).
In addition, skeletal muscle pumping contributes to an increase
in venous return. Cumulatively, these factors in addition to the
actions of the sympathetic nervous system cause cardiac output to
increase to ~20 L/min.
Using the Pressure Volume Relationship to Understand Cardiac Dynamics
We previously considered the functional pressure-volume
curve, as shown on the left. Such curves can be used to
determine a number of parameters regarding the cardiovascular
system, and even to diagnose diseases. As such, it is important
to understand these curves and the principles they reveal.
The functional pressure-volume curve is shown in the area labeled
by “EW” in the curve to the left (EW stands for “external work”, as
discussed later in this lecture). The pressure-volume curves can also
be used to describe all physiological events in the heart.
The diastolic pressure curve is determined by filling the heart
with progressively greater volumes of blood and then measuring
the diastolic pressure immediately before ventricular contraction
occurs, which is the end-diastolic pressure of the ventricle. Thus
curve is often called the end diastolic pressure-volume relationship
(EDPVR).
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Until the volume of the noncontracting ventricle rises above about 150 ml, the “diastolic” pressure
does not increase greatly. Therefore, up to this volume, blood can flow easily into the ventricle from
the atrium. Above 150 ml, the ventricular diastolic pressure increases rapidly, partly because of fibrous
tissue in the heart that will stretch no more and partly because the pericardium that surrounds the heart
becomes filled nearly to its limit.
The systolic pressure curve represents the maximal pressure that can be developed at a particular
filling volume of the ventricle. During ventricular contraction, the “systolic” pressure increases even
at low ventricular volumes and reaches a maximum at a ventricular volume of 150 to 170 ml. Then, as
the volume increases still further, the systolic pressure actually decreases: at these great volumes, the
actin and myosin filaments of the cardiac muscle fibers are pulled apart far enough that the strength of
each cardiac fiber contraction becomes less than optimal.
The systolic pressure curve is usually referred to as the end systolic pressure-volume relationship
(ESPVR). Under physiological conditions, ESPVR is a line that intersects the upper left corner of the
functional pressure volume curve.
It is common for pressure-volume loops to be constructed
from data collected from either experimental animals or
human patients. In patients, a device that measures flow
rates and pressures can be inserted via the femoral artery into
the aorta and then the left ventricle to obtain the necessary
data. It is also possible to obtain the volume of blood in
the ventricle via echocardiography (although pressure
must be measured invasively). As venous return varies
spontaneously, many curves can be generated and plotted
on the same axes. A line is then drawn connecting the upper
left corner of each curve, which is ESPVR.
The upper left corner of the functional pressure-volume curve represents aortic valve closure.
Interestingly, the pressure at this point is generally near mean arterial pressure. Thus, ESPVR shows
the mean arterial pressure generated at different ventricular volumes.
The slope of ESPVR is dependent on the contractility
of the ventricle. Under sympathetic stimulation, the
slope becomes steeper, such that a particular ventricular
volume the pressure is greater. By comparing a normal
pressure-volume loop with one generated at the same
end diastolic volume but under sympathetic stimulation,
the changes in stroke volume resulting from the
manipulation can be determined.
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An increase in contractility has a complex
effect on cardiac output. This is because
mean arterial pressure (and thus afterload)
increases along with the increase in cardiac
output. Hence, an increase in contractility
both facilitates and opposes an increase in
cardiac output. As a result, the increase in
cardiac output is relatively modest.
Increased
Afterload
However, the effects of increased afterload on stroke volume
are ameliorated when contractility increases along with the
afterload, as shown in the graph to the left. In this example,
stroke volume is identical in the normal state and in the state
with combined increases in contractility and afterload.
Inc
rea
sed
Co
ntr
act
ilit
y
The graph to the left shows the effect of a selective
increase in afterload (e.g., resulting from the
Increased administration of an alpha-receptor agonist) on cardiac
Afterload output. Note that ventricular pressure must become
much higher before the aortic valve opens, and the
valve closes much earlier. Consequently, stroke
volume is reduced appreciably.
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An increase in preload results in more filling of the ventricle
during diastole. Consequently, stroke volume increases in
accordance with the additional filling, due to the Frank-Starling
Law of the Heart.
As noted in previous lectures, a variety of factors can contribute
to an increase in preload. They include:
1. Decreased venous compliance (venoconstriction)
Increased
2. Decreased resistance to venous return (RVR)
Preload
3. Increased blood volume
4. Negative intrathoracic pressure
5. Decreased heart rate
6. Decreased ventricular stiffness
7. Supine posture
8. Increased skeletal muscle pumping
Diagnosing Cardiovascular Disease Using the Pressure-Volume Relationship
A number of medical conditions can result in restrictive
cardiomyopathy, or scarring and stiffening of the left
ventricle without a loss of contractility. This condition
results in the EDPVR curve shifting upwards (dashed
line is normal, solid line is during the disease state). As
a result, pressure inside the ventricle increases quickly
as fluid enters the chamber, and thus filling is limited
before intraventricular pressure matches atrial pressure.
Consequently, end-diastolic volume is reduced and stroke
volume decreases.
The situation is even worse in many patients following
a myocardial infarction. Damage to the cardiac muscle
can result in both scarring of the ventricular wall and
loss of contractility. As a result, stroke volume decreases
appreciably (compare the dashed [normal] curve with the
solid [disease state] curve in the diagram to the left.
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Energetics of cardiac contraction
in the chamber.
The area encompassed by the pressurevolume loop is defined as external work or
stroke work, or the work performed by the
ventricle to eject the stroke volume into the
aorta. Stroke work can be estimated by the
product of stroke volume and mean aortic
pressure (SW = SV * MAP). In the graph to
the left, the stroke work is the area labeled
“EW”.
The graph to the left also indicates the area that
represents potential energy (PE). Potential
energy is defined as the energy stored as a
result of deformation of an elastic object. In
the heart, the potential energy is the energy
absorbed by the ventricular wall that does not
result in a change in the pressure of the fluid
The term “pressure-volume area” (PVA) refers to the sum of potential energy and external work.
There is a highly linear correlation between the PVA and cardiac oxygen consumption per beat.
This relationship holds true under a variety of loading and contractile conditions. This estimation of
myocardial oxygen consumption (MVO2) is used to study the coupling of mechanical work and the
energy requirement of the heart in various disease states, such as diabetes, ventricular hypertrophy and
heart failure. MVO2 is also used in the calculation of cardiac efficiency, which is the ratio of cardiac
stroke work to MVO2 (Cardiac Efficiency = SW/MVO2).
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