Conversely, decreasing afterload shifts the curves up and to the left, thereby increasing the stroke volume at any given preload.. Effects of Inotropy on Stroke Volume Effects of Inotrop
Trang 1of as an adaptive mechanism by which the
ventricle is able to offset the increase in wall
stress that accompanies increased aortic
pres-sure, aortic valve stenosis, or ventricular
dila-tion
Effects of Afterload on Frank-Starling
Curves
An increase in afterload shifts the
Frank-Starling curve down and to the right (Fig
4-15) Therefore, at a given preload (LVEDP
in Figure 4-15), an increase in afterload
de-creases stroke volume Conversely, decreasing
afterload shifts the curves up and to the left,
thereby increasing the stroke volume at any
given preload For reasons discussed later,
changes in afterload result in a subsequent
change in preload so that as the
Frank-Starling curve shifts, the operating point for
the curve shifts diagonally, as shown in Figure
4-15 In the normal heart, changes in
after-load do not have pronounced effects on stroke
volume; however, the failing ventricle is very
sensitive to changes in afterload
Effects of Afterload on the Velocity of Fiber
Shortening (Force-Velocity Relationship)
The decrease in stroke volume that
accompa-nies an increase in afterload is caused by
im-paired emptying of the ventricle The basis
for this is found in the force-velocity rela-tionship of cardiac myocytes The
force-velocity relationship shows how afterload af-fects the velocity of shortening when muscle fibers contract isotonically To illustrate this, a papillary muscle is placed in an in vitro bath and a load is attached to one end (Fig 4-16, left panel) When the muscle contracts, the fiber first generates tension isometrically
(right panel, a to b) until the developed
ten-sion exceeds the load imposed on the muscle When this point is reached, the muscle fiber begins to shorten and the tension remains constant and equal to the load that is being
lifted (b to c) The maximal velocity of
short-ening occurs shortly after the muscle begins
to shorten The muscle continues to shorten until the muscle begins to relax When active
tension falls below the load (point c), the
muscle resumes its resting length (i.e.,
pre-load) (point c) Active tension continues to fall isometrically (c to d) until only the passive tension remains (point d).
If this experiment with the papillary mus-cle were repeated with increasing loads, a de-crease would occur in both the maximal ve-locity of fiber shortening (maximal slope of line) and the degree of shortening, as shown
in Figure 4-17 Plotting the maximal velocity
of shortening against the load that the muscle fiber must shorten against (i.e., the afterload) generates an inverse relationship between ve-locity of shortening and afterload (Fig 4-18)
In other words, the greater the afterload, the slower the velocity of shortening.
To further illustrate the force-velocity rela-tionship, consider the following example If a man holds a 2-pound dumbbell at his side while standing, and then contracts his biceps muscle at maximal effort, the weight will be lifted at a relatively high velocity as the biceps muscle shortens If the weight is increased to
20 pounds, and the weight once again is lifted
at maximal effort, the velocity will be much slower Higher weights further reduce the ve-locity until the weight can no longer be lifted and the contraction of the biceps muscle be-comes isometric The x-intercept in the force velocity diagram (see Fig 4-18) is the point at 10
100
50
20 0
0
LVEDP (mmHg)
B A C
FIGURE 4-15 Effects of changes in afterload on
Frank-Starling curves An increase in afterload shifts the
oper-ating point of the Frank-Starling curve from A to B,
whereas a decrease in afterload shifts the operating
point from A to C Therefore, increased afterload
de-creases stroke volume and inde-creases end-diastolic
pres-sure (preload) The converse also is true.
Trang 2which the afterload is so great that the muscle
fiber cannot shorten The x-intercept
there-fore represents the maximal isometric force
The y-intercept represents an extrapolated
value for the maximal velocity (Vmax) that
would be achieved if there was no afterload
The value is extrapolated because it cannot be
measured experimentally (a muscle will not
contract in the absence of any load)
It is important to note that a cardiac muscle
fiber does not operate on a single
force-velocity curve (Fig 4-19) If preload is
in-creased, a cardiac muscle fiber will have a
greater velocity of shortening at a given
after-load This occurs because the length-tension relationship requires that as the preload is in-creased, there is an increase in active tension development Once the fiber begins to shorten,
an increased preload with an increase in ten-sion-generating capability causes a greater shortening velocity In other words, increasing the preload enables the muscle to contract faster against a given afterload; this shifts the force-velocity relationship to the right Note that increasing the preload increases the maxi-mal isometric force (x-intercept) as well as the shortening velocity at a given afterload Changes in preload, however, do not alter V
Length Tension
Time
∆
∆
L
T
Preload Resting Maximal
Minimal
∆ L Muscle
Load
a
d
FIGURE 4-16 Cardiac muscle isotonic contractions The left panel shows how muscle length and tension are mea-sured in vitro The lower end of the muscle is attached to a weight (load) that is lifted up from an immovable plat-form as the muscle develops tension and shortens (∆L) A bar attached to the top of the muscle can be moved to
adjust initial muscle length (preload) The right panel shows changes in tension and length during contraction The
periods from a to b and from c to d represent periods of isometric contraction and relaxation, respectively Muscle
shortening (∆L) occurs between b and c, which occurs when the developed tension (∆T) exceeds the load.
Decreasing
Length
Time b
a c = increasing afterload
a
c Preload
FIGURE 4-17 Effects of afterload on myocyte
shorten-ing Increased afterload (curves a to c) decreases the
de-gree of muscle shortening and velocity of shortening at
a given preload.
Afterload (Force)
Maximal Isometric Force Vmax
FIGURE 4-18 Force-velocity relationship Increased af-terload (which requires increased force generation) de-creases velocity of shortening by the muscle fiber The x-intercept represents the maximal isometric force; the y-intercept represents the maximal velocity of
shorten-ing (V max) extrapolated to zero load.
Trang 3Therefore, an increase in preload on a cardiac
myocyte helps to offset the reduction in velocity
that occurs when afterload is increased.
Effects of Afterload on Pressure-Volume
Loops
Changes in afterload produce secondary
changes in preload, as shown in Figure 4-15
Therefore, afterload and preload are
interde-pendent variables This interdependence can
best be described using pressure-volume loops
(Fig 4-20) If afterload is increased by
increas-ing aortic diastolic pressure, the ventricle has
to generate increased pressure before the
aor-tic valve can open The ejection velocity after
the valve opens will be reduced because
in-creased afterload decreases the velocity of
car-diac fibers shortening, as described by the
force-velocity relationship Because only a
fi-nite period of time exists for electrical and
me-chanical systole, less blood will be ejected
(de-creased stroke volume) so that ventricular
end-systolic volume increases as shown in the
pressure-volume loop The increased
end-sys-tolic volume inside the ventricle will be added
to the venous return, thereby increasing
end-diastolic volume After several beats, a steady
state is achieved in which the increase in
end-systolic volume is greater than the increase in
end-diastolic volume so that the difference
be-tween the two—the stroke volume—is
de-creased (i.e., the width of the pressure-volume
loop is decreased) This increase in preload
secondary to the increase in afterload activates
the Frank-Starling mechanism to partially compensate for the reduction in stroke volume caused by the increase in afterload
Effects of Inotropy on Stroke Volume
Effects of Inotropy on Length-Tension Relationship
Ventricular stroke volume is altered both by changes in preload and afterload, and by
changes in ventricular inotropy (sometimes
referred to as contractility) Changes in ino-tropy are caused by intrinsic cellular mecha-nisms that regulate the interaction between actin and myosin independent of changes in sarcomere length For example, if cardiac
mus-cle is exposed to norepinephrine, it increases active tension development at any initial pload length as shown by the length-tension re-lationship (Fig 4-21) This occurs because the norepinephrine binds to 1-adrenoceptors, in-creasing calcium entry into the cell and cal-cium release by the sarcoplasmic reticulum during contraction (see Chapter 3)
Effects of Inotropy on Force-Velocity Relationship
Changes in inotropy also alter the force-veloc-ity relationship If the inotropic state of the
Afterload (Force)
Increasing Preload a c
FIGURE 4-19 Effects of increasing preload (shift from
curve a to c) on the force-velocity relationship At a
given afterload, increasing the preload increases the
ve-locity of shortening Furthermore, increasing the
pre-load shifts the x-intercept to the right, representing an
increase in isometric force generation.
LV Volume (ml)
Control Loop
Increased Aortic Pressure
FIGURE 4-20 Effects of increased afterload (aortic
pres-sure) on the steady-state left ventricular (LV)
pressure-volume loop Heart rate and inotropy are held constant
in this illustration Increased aortic pressure leads to an
increase in end-systolic volume (ESV), followed by a
sec-ondary, but smaller increase in end-diastolic volume
(EDV) The net effect is a narrower loop and therefore
decreased stroke volume.
Trang 4myocyte is increased, the force-velocity curve
has a parallel shift up and to the right,
result-ing in an increase in both Vmax and maximal
isometric force (Fig 4-22) The increase in
ve-locity at any given afterload results from the
increased inotropy enhancing force
genera-tion by the actin and myosin filaments and
in-creasing the rate of cross-bridge turnover The
increase in Vmax represents an increased
in-trinsic capability of the muscle fiber to
gener-ate force independent of load
Effects of Inotropy on Pressure-Volume
Loops
The increased velocity of fiber shortening that
occurs with increased inotropy causes an
in-creased rate of ventricular pressure
develop-ment (dP/dt) This increases ejection velocity
and stroke volume and reduces end-systolic
volume, as shown in Figure 4-23 When
ino-tropy is increased, the end-systolic
pressure-volume relationship is shifted to the left and
becomes steeper, because the ventricle can
generate increased pressure at any given
vol-ume The end-systolic pressure-volume
rela-tionship sometimes is used experimentally to
define the inotropic state of the ventricle It is
analogous to the upward shift that occurs in the total tension curve in the length-tension relationship (Fig 4-21) when inotropy in-creases Furthermore, the increased stroke volume leads to a reduction in ventricular end-diastolic volume because less end-systolic volume is available to be added to the incom-ing venous return
Increased Inotropy
Length
Passive Tension
Total Tension
FIGURE 4-21 Effects of increased inotropy on the
length-tension relationship for cardiac muscle
In-creasing inotropy (for example, by stimulating the
car-diac muscle with norepinephrine) shifts the total
tension curve upward, which increases active tension
development (vertical arrows) at any given preload
length.
Afterload (Force)
Increasing Inotropy a c
FIGURE 4-22 Effects of increasing inotropy (parallel
shift from curve a to c) on the force-velocity
relation-ship Increased inotropy increases the velocity of short-ening at any given afterload, and increases V max (y-in-tercept) Furthermore, increased inotropy increases maximal isometric force (x-intercept).
LV Volume (ml)
Increased Inotropy
Control Loop
FIGURE 4-23 Effects of increasing inotropy on the steady state of the left ventricular pressure-volume loop Heart rate and aortic pressure are held constant in this illustration Increased inotropy shifts the end-sys-tolic pressure-volume relationship (see Fig 4-4) up and
to the left, thereby decreasing end-systolic volume
(ESV) A secondary, but smaller decrease in end-diastolic volume (EDV) follows The net effect is an increase in stroke volume (EDV – ESV) LV, left ventricle.
Trang 5Effects of Inotropy on Frank-Starling
Curves
An increase in inotropy causes the
Frank-Starling curve to shift up and to the left (Fig
4-24) This leads to an increase in stroke
vol-ume along with a reduction in ventricular
pre-load Conversely, a decrease in inotropy (as
occurs in systolic heart failure; see Chapter 9),
shifts the relationship down and to the right,
thereby decreasing stroke volume and
in-creasing preload
Changes in inotropy change the ejection fraction, which is defined as the stroke
vol-ume divided by the end-diastolic volvol-ume A
normal ejection fraction is greater than 0.55
(or 55%) Increasing inotropy increases
ejec-tion fracejec-tion, whereas decreasing inotropy
de-creases ejection fraction Therefore, ejection
fraction often is used as a clinical index for
evaluating the inotropic state of the heart In
heart failure, for example, a decrease in
in-otropy leads to a fall in stroke volume as well
as an increase in preload, thereby decreasing
ejection fraction sometimes to a value less
than 20% Treating a patient in heart failure
with an inotropic drug (e.g.,
agonist or digoxin) shifts the depressed
Frank-Starling curve up and to the left, thereby
in-creasing stroke volume, dein-creasing preload, and increasing ejection fraction
Changes in inotropic state are particularly important during exercise (see Chapter 9) Increases in inotropic state help to maintain stroke volume at high heart rates Increased heart rate alone decreases stroke volume be-cause of reduced time for diastolic filling (de-creased end-diastolic volume) When ino-tropic state increases at the same time, this decreases end-systolic volume to help main-tain stroke volume
Factors Influencing Inotropic State
Several factors influence inotropy (Fig 4-25); the most important of these is the activity of autonomic nerves Sympathetic nerves, by re-leasing norepinephrine that binds to 1 -adrenoceptors on myocytes, are prominent in ventricular and atrial inotropic regulation (see Chapter 3) Parasympathetic nerves (vagal ef-ferents), which release acetylcholine that binds to muscarinic (M2) receptors on my-ocytes (see Chapter 3), have a significant neg-ative inotropic effect in the atria but only a small effect in the ventricles High levels of circulating epinephrine augment sympathetic adrenergic effects via 1-adrenoceptor activa-tion In humans and some other mammalian hearts, an abrupt increase in afterload can
cause a modest increase in inotropy (Anrep effect) by a mechanism that is not fully
un-derstood In addition, an increase in heart rate can cause a small positive inotropic effect
(also termed the Bowditch effect, treppe, or
frequency-dependent activation) This latter phenomenon probably is due to an inability of the Na/K-ATPase to keep up with the sodium influx at higher frequency of action potentials at elevated heart rates, leading to an accumulation of intracellular calcium via the sodium-calcium exchanger (see Chapter 2) Systolic failure that results from cardiomyopa-thy, ischemia, valve disease, arrhythmias, and other conditions is characterized by a loss of intrinsic inotropy In addition to these physio-logic and pathophysio-logic mechanisms, a variety of inotropic drugs are used clinically to increase inotropy in acute and chronic heart failure These drugs include digoxin (inhibits
sar-10
100
50
20 0
0
LVEDP (mmHg)
B
A C
FIGURE 4-24 Effects of changes in inotropy on
Frank-Starling curves Decreased inotropy shifts the operating
point from A to B, which decreases stroke volume and
increases left ventricular end-diastolic pressure (LVEDP).
Increased inotropy causes a shift from point A to C,
which increases stroke volume and decreases LVEDP.
Trang 6colemmal Na/K-ATPase),
agonists (e.g., dopamine, dobutamine,
epi-nephrine, isoproterenol), and
phosphodi-esterase inhibitors (e.g., milrinone)
Mechanisms of Inotropy
Inotropy can be thought of as a length-inde-pendent activation of the contractile
pro-teins Any cellular mechanism that ultimately
A 67-year-old male is diagnosed with left ventricular failure 4 months following an acute myocardial infarction One of the drugs he is given for treatment acts as a systemic arte-rial vasodilator Using Frank-Starling curves and left ventricular pressure-volume loops, explain how decreasing afterload will improve left ventricular ejection fraction.
A systemic vasodilator reduces afterload on the left ventricle This causes the Starling curve to shift up and to the left from its depressed state (because of the loss of inotropy in failure) (left figure) This shift increases stroke volume and at the same
time reduces preload (end-diastolic pressure) from point A to B in left figure Systemic vasodilation reduces aortic diastolic pressure, which enables the ventricle to eject
sooner, more rapidly, and to a smaller end-systolic volume (right figure) The reduced end-systolic volume leads to a compensatory decrease in end-diastolic volume; how-ever, the reduction in systolic volume will be greater than the reduction in end-diastolic volume so that stroke volume is increased By increasing stroke volume and reducing the end-diastolic volume, the ejection fraction is increased
C A S E 4 - 3
10
100
50
20 0
0
LVEDP (mmHg)
B
A
Non-failing Heart
Failing Heart
LV Volume (ml)
200
100
0
Heart Failure
Arterial Dilator plus
Heart Failure Loop
Effects of an arterial vasodilator on stroke volume
and left ventricular end-diastolic pressure (LVEDP) in
heart failure In heart failure (specifically systolic
fail-ure – see Chapter 9), the Frank-Starling curve shifts
downward because of depressed inotropy Arterial
vasodilation, which reduces afterload on the
ventri-cle, moves the operating point from A to B by
shift-ing the Frank-Starlshift-ing curve upward This leads to an
increase in stroke volume and a decrease in LVEDP
(preload).
Effects of an arterial vasodilator on left ventricular pressure-volume loops Heart failure causes a down-ward shift (reduced slope) of the end-systolic pres-sure-volume relationship This leads to an increase in end-systolic volume, a smaller compensatory in-crease in end-diastolic volume, and reduced stroke volume Reducing arterial pressure decreases afterload on the ventricle, which leads to an increase
in stroke volume This decreases left ventricular systolic volume, and to a smaller extent, end-diastolic volume The net effect is an increase in
stroke volume LV, left ventricle.
Trang 7alters myosin ATPase activity at a given
sar-comere length alters force generation and
therefore can be considered an inotropic
mechanism Most of the signal transduction
pathways that regulate inotropy involve Ca
(see Chapter 3) Briefly, inotropic state can be
enhanced by (1) increasing Cainflux across
the sarcolemma during the action potential
(via L-type Cachannels); (2) increasing the
release of Ca by the sarcoplasmic
reticu-lum; or (3) sensitizing troponin C to Ca For
example, 1-adrenoceptor activation acting
through Gs-proteins increases cAMP, which
activates protein kinase-A This enzyme can
phosphorylate different intracellular sites to
influence Caentry, Carelease, and Ca
affinity Cardiac glycosides such as digoxin
in-hibit the Na/K-ATPase, leading to an
in-crease in intracellular Caand an increase in
inotropy
MYOCARDIAL OXYGEN
CONSUMPTION
Changes in stroke volume, whether caused by
changes in preload, afterload, or inotropy,
sig-nificantly alter the oxygen consumption of the
heart Changes in heart rate likewise affect
myocardial oxygen consumption The
con-tracting heart consumes a considerable
amount of oxygen because of its need to
re-generate the large amount of ATP hydrolyzed
during contraction and relaxation Therefore,
any change in myocardial function that affects
either the generation of force by myocytes or
their frequency of contraction will alter oxy-gen consumption In addition, even in non-contracting cells, ATP utilized by ion pumps and other transport functions requires oxygen for the resynthesis of ATP
How Myocardial Oxygen Consumption is Determined
Oxygen consumption is defined as the volume
of oxygen consumed per min (e.g., mL
O2/min) and is sometimes expressed per 100 g
of tissue weight (mL O2/min per 100 g) The myocardial oxygen consumption (MVO2) can
be calculated by knowing the coronary blood flow (CBF) and the arterial and venous oxy-gen contents (AO2and VO2) according to the
following equation that uses the Fick Principle:
MVO2 CBF (AO2 VO2) Myocardial oxygen consumption, there-fore, is equal to the coronary blood flow mul-tiplied by the amount of oxygen extracted from the blood (the arterial-venous oxygen difference) The content of oxygen in blood is usually expressed as mL O2/100 mL blood (or, vol % O2) The oxygen content of arterial blood is normally about 20 mL O2/100 mL blood To calculate the myocardial oxygen consumption in the correct units, mL O2/100
mL blood is converted to mL O2/mL blood; with this conversion, the arterial oxygen con-tent is 0.2 mL O2/mL blood For example, if CBF is 80 mL/min per 100 g, the AO is 0.2
Catecholamines
Heart Rate (Bowditch Effect) Systolic
Failure
Afterload (Anrep Effect)
Sympathetic Activation Parasympathetic
Activation
_
_
Inotropic State (Contractility)
+ +
FIGURE 4-25 Factors regulating inotropy ( ), increased inotropy; (), decreased inotropy.
Eq 4-3
Trang 8mL O2/mL blood and VO2 is 0.1 mL O2/mL
blood, MVO2 8 mL O2/min per 100 g This
value of myocardial oxygen consumption is
typical for what is found in a heart contracting
at resting heart rates against normal aortic
pressures During heavy exercise, myocardial
oxygen consumption can increase to 70 mL
O2/min per 100 g, or more If contractions are
arrested (e.g., by depolarization of the heart
with a high concentration of potassium
chlo-ride), the myocardial oxygen consumption
de-creases to about 2 mL O2/min per 100g This
value represents the energy costs of cellular
functions not associated with contraction
Therefore, myocardial oxygen consumption
varies considerably depending on the state of
mechanical activity
Although myocardial oxygen consumption
can be calculated as described above,
gener-ally it is not feasible to measure coronary
blood flow and venous oxygen content except
in experimental studies Coronary blood flow
can be measured by placing flow probes on
coronary arteries or a thermodilution catheter
within the coronary sinus Arterial oxygen
content can be taken from a peripheral artery,
but the venous oxygen content has to be
ob-tained from the coronary sinus by inserting a
catheter into the right atrium and then into
the coronary sinus
Indirect indices of myocardial oxygen
con-sumption have been developed to estimate
myocardial oxygen consumption when it is not feasible to measure it Although no index has proven to be satisfactory over a wide range of physiologic conditions, one simple index
sometimes used in clinical studies is the pres-sure-rate product (also called the
double-product) This index can be measured nonin-vasively by multiplying heart rate and systolic arterial pressure (mean arterial pressure sometimes is used instead of systolic arterial pressure) The pressure-rate product assumes that the pressure generated by the ventricle is not significantly different than the aortic pres-sure (i.e., there is no aortic valve stenosis) Experiments have shown that a reasonable correlation exists between changes in the pressure-rate product and myocardial oxygen consumption For example, if arterial pres-sure, heart rate, or both become elevated, oxy-gen consumption will increase
Factors Influencing Myocardial Oxygen Consumption
Part of the difficulty in finding a suitable index
of oxygen consumption is that several factors determine myocyte oxygen consumption, in-cluding frequency of contraction, inotropic state, afterload, and preload (Table 4-1) For example, doubling heart rate approximately doubles oxygen consumption, because myo-cytes are generating twice the number of
ten-In an experimental study, administration of an inotropic drug is found to increase coro-nary blood flow (CBF) from 50 to 150 mL/min and increase the arterial-venous oxygen difference (AO 2 – VO 2 ) from 10 to 14 mL O 2 /100 mL blood Calculate the percent in-crease in myocardial oxygen consumption (MV O 2 ) caused by infusion of this drug.
Myocardial oxygen consumption can be calculated from Equation 4-3, such that
MVO2 CBF (AO2 VO2) The control oxygen consumption is 50 mL/min times the A-V oxygen difference of 0.1 mL O2/mL blood, which equals 5 mL O2/min Note that the arterial-venous oxygen difference must be converted from mL O2/100 mL blood to mL O2/mL blood The experi-mental oxygen consumption is 150 mL/min times 0.14 mL O2/mL blood, which equals 21
mL O2/min This is a 320% increase in oxygen consumption ([(21 -5)/5] x 100)
P R O B L E M 4 - 3
Trang 9sion cycles per minute Increasing inotropy
in-creases oxygen consumption because both the
rate of tension development and the
magni-tude of tension are increased, and they both
are associated with increased ATP hydrolysis
and oxygen consumption An increase in
af-terload likewise increases oxygen
consump-tion because it increases the tension that must
be developed by myocytes Increasing stroke
volume by increasing preload (end-diastolic
volume) also increases oxygen consumption
Quantitatively, increased preload has less impact on oxygen consumption than does an
increase in afterload (e.g., aortic pressure) To
understand why, we need to examine the
rela-tionship between wall stress, pressure, and
ra-dius of the ventricle As discussed earlier (see
Equation 4-2), ventricular wall stress () is
proportional to the intraventricular pressure
(P) multiplied by the ventricular internal
ra-dius (r) and divided by the wall thickness (h)
∝ Wall stress is related to the tension an indi-vidual myocyte must develop during
contrac-tion to generate a given ventricular pressure
At a given radius and wall thickness, a
my-ocyte must generate increased contractile
force (i.e., wall stress) to develop a higher
pressure The contractile force must be
in-creased even further to generate the same
el-evated pressure if the ventricular radius is
in-creased For example, if the ventricle is
required to generate 50% more pressure than
normal to eject blood because of elevated
aor-P r
h
tic pressure, the wall stress that individual myocytes must generate will be increased by approximately 50% This will increase the oxy-gen consumption of these myocytes by about 50% because changes in oxygen consumption are closely related to changes in wall stress As
a second example, if the radius of the ventri-cle is increased by 50%, the wall stress needed
by the myocytes to eject blood at a normal pressure will be increased by about 50% On the other hand, if the ventricular end-diastolic volume is increased by 50% and the pressure and wall thickness remain unchanged, the wall stress will be increased by only about 14% The reason for this is that a large change
in ventricular volume (V) requires only a small change in radius (r) If we assume that the shape of the ventricle is a sphere, then
V r3
By rearranging this relationship, we find that
r ∝3V Substituting this into the wall stress equation results in
∝ Although no single acceptable model for the shape of the ventricle exists because its shape changes during contraction, a sphere serves as
a convenient model for illustrating why changes in volume have a relatively small af-fect on wall stress and oxygen consumption Using this model, Equation 4-4 shows that in-creasing the end-diastolic volume by 50% (by
a factor of 1.5) represents only a 14% (cube root of 1.5) increase in wall stress at a given ventricular pressure, whereas a 50% increase
in pressure increases wall stress by 50% Therefore, increasing pressure by a given per-centage increases wall stress about four times more than the same change in volume Relating the wall stress equation to oxygen consumption helps to explain why increases in pressure generation have a much greater in-fluence on oxygen consumption than a similar percentage increase in ventricular preload It
is important, however, not to use the wall
P 3V h
4 3
TABLE 4-1 FACTORS INCREASING
MYOCARDIAL OXYGEN
CONSUMPTION
↑ Heart Rate
↑ Inotropy
↑ Afterload
↑ Preload*
*Changes in preload affect oxygen consumption
much less than do changes in the other factors.
Eq 4-4
Trang 10stress equation to estimate oxygen demands
by the whole heart The reason for this is that
wall stress estimates the tension required by
individual myocytes to generate pressure as
they contract This wall stress, in large part,
determines the oxygen consumption of
indi-vidual myocytes, but oxygen consumption of
the whole heart is the sum of the oxygen
con-sumed by all of the myocytes A
hypertro-phied ventricle with a thicker wall, which has
reduced wall stress, may not have a reduction
in overall oxygen consumption as suggested by
Equation 4-4 In fact, because of its greater
muscle mass, oxygen consumption may be
sig-nificantly increased in a hypertrophied heart,
particularly if its efficiency is impaired by
dis-ease A less efficient heart performs less work
per unit oxygen consumed (i.e., it generates
less pressure and stroke volume)
The concepts described above have
impli-cations for treating patients with coronary
artery disease (CAD) For example, drugs that
decrease afterload, heart rate, and inotropy
are particularly effective in reducing
myocar-dial oxygen consumption and relieving
symp-toms of chest pain (i.e., angina), which results
from inadequate oxygen delivery relative to
the oxygen demands of the myocardium
CAD patients are counseled to avoid activities
such as lifting heavy weights that lead to large
increases in arterial blood pressure In
con-trast, CAD patients are often encouraged to
participate in exercise programs such as
walk-ing that utilize preload changes to augment
cardiac output by the Frank-Starling
mecha-nism It is important to minimize stressful
sit-uations in these patients because stress causes
sympathetic activation of the heart and
vascu-lature that increases heart rate, inotropy, and
afterload, all of which lead to significant
in-creases in oxygen demand by the heart
SUMMARY OF IMPORTANT
CONCEPTS
• The cardiac cycle is divided into two
gen-eral phases: diastole and systole Diastole
refers to the period of time that the
ventri-cles are undergoing relaxation and filling
with blood from the atria Ventricular filling
is primarily passive, although atrial contrac-tion has a variable effect on the final extent
of ventricular filling (end-diastolic volume) Systole, or ventricular contraction, is initi-ated by electrical depolarization of the ven-tricles, which is represented by the QRS complex of the electrocardiogram Ventricular ejection begins when ventricu-lar pressure exceeds the pressure within the outflow tract (aorta or pulmonary artery) and continues until ventricular relaxation causes the ventricular pressures to fall suffi-ciently below the aortic and pulmonary artery pressures to cause the aortic and pul-monic valves to close The volume of blood remaining in the ventricle at the end of ejection is the end-systolic volume
• The first heart sound (S1) originates from closure of the atrioventricular valves (tri-cuspid and mitral) as the ventricles begin to contract The second heart sound (S2) re-sults from the closure of the pulmonic and aortic valves at the end of ventricular sys-tole The third and fourth heart sounds (S3 and S4), when audible, occur during early diastole and atrial contraction, respectively
• Ventricular stroke volume is the difference between the end-diastolic and end-systolic volumes Ventricular ejection fraction is calculated as the stroke volume divided by the end-diastolic volume Ejection fraction
is frequently used in a clinical setting to as-sess the inotropic state of the left ventricle
• Cardiac output is the product of stroke vol-ume and heart rate Normally, cardiac out-put is influenced more by changes in heart rate than by changes in stroke volume; however, impaired regulation of stroke vol-ume can have a significant adverse affect
on cardiac output, as occurs during heart failure
• Ventricular preload is related to the extent
of ventricular filling (end-diastolic volume) and the sarcomere length Preload can be increased by several factors: increased blood volume, augmented venous return, decreased venous compliance (venous con-striction), atrial contraction force, and de-creased heart rate (increases filling time); indirectly, preload can be increased by a