CARDIO PHYSIOLOGY PPT NOTES

4
Although we could say that among the those
described above the transport of essential
substances to the tissues may be the most
significant function of the circulatory system , as
you can see all of the other factors are of
paramount importance in the maintenance of
internal homeostasis. Each function depends on the
other. For example, if the subcutaneous and muscle
circulation does not increase during strenuous
exercise, the body is not capable of releasing the
heat produced by the higher metabolism. The
result is hyperthermia with eventual heat shock
and death.
5
Our circulatory system is a closed circuit
containing a pump (the heart) that serves to
maintain a pressure gradient sufficient to sustain
an effective blood flow from the distributing ducts
or arteries to the thin vessels or capillaries and
back through the collecting ducts or veins. Two
circuits, the pulmonary and systemic are present.
The pulmonary may be considered the low pressure
circuit while the systemic is the high pressure one.
6
The pressure in our systemic circulation drops
gradually from an initial 120mm Hg in the aorta to
a minimum of 2mm Hg in the Vena Cava. The main
drop in pressure occurs in the resistance vessels or
arterioles which are highly muscular and well
regulated by nervous and humoral factors. They
are also muscular arteries containing a high
proportion of vascular smooth muscle in the vessel
walls. Compare them to the aorta and veins in
terms of elastic tissue/smooth muscle content. At
2mm Hg in the inferior vena cava, what factors do
you think propel blood into the right heart from the
lower parts of the body?
7
Systemic arteries are mainly pressure vessels.
Their walls contain a higher proportion of elastic
and muscular tissue than veins. They are vessels
with less capacity to distend than veins . Veins
on the contrary are mainly capacitance vessels
and can distend more in response to an increase
in blood volume. Since both arteries and veins
are interconnected by the capillaries and the whole
closed system is filled with a volume of blood, a
greater fraction of the total blood volume will
accommodate in the veins that can distend more
easily. The values of blood volume distribution

given above are for a fully functional system in

which the heart is pumping. What do you think
would happen if the heart stopped?
8
Our closed circulatory system has evolved into a
series- parallel circuit design. The parallel
system allows for the redirecting of blood flow
to specific areas when needed.
A good example is the redirection of flow into the
subcutaneous and muscular circulations during
strenuous exercise. On the other hand, during
digestion blood flow increases dramatically in the
GI circulation in order to supply the gastrointestinal
system with the necessary elements to support
the increased metabolic activity . Humoral factors
are mainly responsible for the regulation of local
circulatory circuits but some nervous components
are also present.
9
At the end of this section you should be able
to:
1. Recognize the main factors involved in the
generation of a resting membrane potential.
2. Describe all the electrophysiological events that
lead to the fast and slow cardiac fibers action
potentials.
3. Explain the effect of calcium channel blockers on
the fast and slow cardiac fibers action potential.
4. Explain what is meant by Effective Refractory
period and Absolute Refractory Period.
5. Recognize the factors that affect conduction of
the action potential in the heart
6. Explain the effect of myocardial infarction and
potassium on action potential conduction.
7. Explain the concept of post-repolarization
refractoriness.
8. Recognize the mechanism involved in the
generation of the pacemaker potential.
9. Understand the effects of adrenergic and
cholinergic stimulation on the pacemaker potential.
10. Explain what is overdrive suppression .
11. Explain the concept of nodal delay and its
importance in cardiac stimulation.
12. Electrocardiographically recognize 1st,2nd and
3rd degree AV Blocks

10
Yes, you must remember these equations always.
The first two are Nernst equations for equilibrium
potentials of potassium and sodium respectively.
The last one is the Goldman equation that takes
into account the effect of other ions and their
permeability coefficients (P). If you consider that
the permeability of potassium is 100 times higher
than that of sodium then the effect of sodium and
chloride becomes negligible in the Goldman
equation and for all practical purposes it becomes
the Nernst equation for potassium.
Do you remember what Ek or ENa really means? If
you dont please review Dr. Escobales notes right
now.
11
Like in many other cells the resting membrane
potential of the cardiomyocite depends mainly on
the diffusion of potassium from the intracellular
to the extracellular compartment. If you consider
that, for practical purposes only, the cell
membrane is permeable mainly to potassium,
then ,as potassium diffuses out of the cell following
its concentration gradient, positive charges
move out of the cell not accompanied by
negative charges. This creates a very small region
of positive charge in the outer part of the cell
membrane and consequently another very small
region of negative charge inside. The negative
charge inside tends to keep the K+ inside the cell
and works against the chemical force created by
the concentration gradient that tends to move K+
out of the cell. When both forces are equal net K+
movement across the membrane is zero and a
potential difference has been established across
the cell membrane.
12
If you use the normal intra and extracellular
concentrations of Na+ or Ca++ to calculate the
resting membrane potential of a myocardial cell
the values obtained deviate significantly from the
experimentally measured values. Thus, the
distribution of these ions across the cell membrane
does not explain the measured resting membrane
potential. When the extra and intracellular
concentrations of K+ are used in the Nernst
equation the value obtained for Em approximates
the measured value indicating that K+ is a major
factor in the resting membrane potential. In
addition when the permeability of K+ and Na+ are
compared, K+ shows up as 100 times more
permeable than Na+. K+ becomes a very

important and CLINICALLY RELEVANT ion in

cardiac function. More later.
13
Microelectrodes placed in individual cells of the
atria, ventricles and sinoatrial node show distinct
action potential profiles. You should recognize
these profiles at first sight and without
hesitation. Between the atrial and ventricular
action potential profiles the main differences lie in
the plateau phase that is more pronounced in the
ventricular cell. The nodal cell action potential is
easy to recognize since there is no plateau phase,
the depolarization phase is slower than in the atrial
or ventricular cell and the resting membrane
potential is achieved briefly as the cell continues to
depolarize automatically until the next action
potential is triggered.
14
Both atrial and ventricular fibers are fast response
types. The graph above shows an
electrophysiological recording obtained from a
single ventricular fiber. To obtain the recording a
microelectrode is placed in the intacellular
compartment of the cell and a second
microelectrode is left outside as a reference. The
very small signal is then amplified (AMP) and sent
to the horizontal plates of an oscilloscope. As the
cell depolarizes and repolarizes in each action
potential we can measure the voltage in the
vertical deflection of the oscilloscope electron
beam. The horizontal deflection of the beam gives
us the time. For the ventricular cell the action
potential has been divided into 4 phases. Phase 0 is
the rapid depolarization, phase 1 is a transient
repolarization, phase 2 is the plateau phase, phase
3 is the repolarization phase and phase 4 is the
resting potential phase. You must know these
phases well!!Now for the details. (pages 7
and 8 B&L)
15
Phase 0 is the depolarization phase of the fast
fiber action potential and its mostly dependent on
the opening of fast Na+ channels in the cell
membrane controlled by m (activation gates) and h
(inactivation gates). At the resting membrane
potential (A) the activation gates m close the
channel maintaining Na+ out of the cell. The
electrical and chemical gradient for Na+ favor its
entry into the cell (arrows). When the cell
depolarizes and the membrane potential drops to
near -65mv (B), the m gate moves out of the
channel leaving an opening through which Na+ can
move into the cell. As Na+ moves into the cell the

electrical gradient that promoted its entry

dissipates and then reverses (C to E). The chemical
gradient continues to promote Na+ entry (black
arrow). After reaching about +30mv the h gate
closes or inactivates the channel ending the rapid
depolarization phase or phase 0. As the cell
repolarizes the gates are returned to their normal
resting state (A). This is the tetrodotoxin sensitive
phase of the cardiac cell action potential. (see
pages 13 to18 B&L)
16
Three K+ channels are involved in the
repolarization period of the fast fiber action
potential. The small repolarization that occurs in
phase one depends on the Ito channels. This
channels are also important in the final
repolarization period and in fact if you observe an
atrial cell action potential, the Ito effect will be
more pronounced thus shortening the plateau
period or phase 2. In phase 2 the K+ efflux through
the Ito,Ik and Ikl channels cannot counteract the
Ca++ influx and the potential remains unchanged.
Later on the three K+ currents counteract the Ca+
+ influx and repolarize the cell in Phase 3. It is in
this phase that the Ik channels have a significant
effect. As the membrane potential increases during
repolarization from -20 to -70mv the Ikl channels
acquire more significance and become a major
factor in repolarization and eventual maintenance
of the resting membrane potential (see pages
21,22,23 B&L)
17
L and T type calcium channels open during phase 0
of the fast fiber action potential. The L channels or
Long Lasting open rapidly but deactivate slowly.
These are the most abundant of the Ca++
channels. The T channels or Transient channels
open before the L type but close much more
rapidly. The opening of the Ca++ channels brings a
huge influx of Ca++ into the cell that coupled to
the efflux of K+ maintain the membrane potential
almost unchanged for a period of time. This is the
cause of the plateau phase of the fast fiber action
potential. Eventually the Ca++ channels close and
K+ efflux predominates bringing about the
eventual repolarization. Please note that the L Type
Ca++ channels are the ones in which the calcium
blockers have their inhibitory effect. Remember
also that the Ca++ that enters the fast fiber during
Phase 2 is actively used for contraction. (see pages
19,20 B&L)
18

The effect of Diltiazem, an L Type Ca++ channel

blocker is clearly observed in the figure. Notice that
as the dose of Diltiazem is increased, the plateau
phase decreases. This means that we are letting
the K+ currents have an upper hand so that
repolarization in phase 3 begins much earlier.
In fact with the higher dose of diltiazem the original
fast fiber potential that looked like a ventricular cell
action potential starts to take the characteristics of
an atrial cell action potential. Notice also the
consequent decrease in the force of contraction
elicited by Diltiazem. What clinical applications
can you infer from this graph?
(see page 22, B&L)
19
So why do I have to know each stage of the fast
fiber action potential and which ions are
responsible for each stage. Because one of the
most important clinical arrhythmias is due to
an improper action potential. An early after
depolarization is produced when the preceding
action potential leaves an oscillating voltage in
the myocardial cell membrane. This means that
the myocardial cell never fully repolarizes and is
maintained in a partially depolarized state. This
electrical instability may cause de myocardial cell
to once again become depolarized before hand.
Thus producing the red curve shown above. In this
example the depolarization occurs in phase 2 of the
action potential, and thus is termed an Early After
Depolarization. Something really important to
remember in this case is which IONS are
responsible for this after-depolarization. SOOO
which is it???? Simple, look at the membrane
potential at the time the after-depolarization shoots
up (red curve)! Its about 0 mV. This means that
almost all of the Na channels are closed or
refractory. Thus the only Ion that could exert such
an upstroke in depolarization is Ca. Indeed it is Ca
who is responsible for this depolarization. These
Early after-depolarizations can occur at any time
and can continue for many cardiac beats. They
have nothing to do with re-entry circuits or ectopic
pacemakers, they are merely the result of a
preceding action potential which leaves an
oscillating membrane potential.
These early after-depolarizations can be
viewed in the EKG as a very dangerous arrhythmia
called Torsades de Pointes, or Torsion of the Points
which is shown on the green EKG above.
20

QUICK REVIEW OF THE FAST FIBER ACTION

POTENTIAL.
REVIEW THE FIGURE ABOVE AND ALL THE DETAILS
IN IT. REMEMBER THAT WHAT YOU HAVE LEARNED
ABOUT THE FAST FIBER ACTION POTENTIAL HAS
IMPORTANT CLINICAL IMPLICATIONS!
ONE GOOD WAY TO REVIEW THIS IS TO BLOCK THE
EVENTS OF EACH PHASE WITH A PIECE OF PAPER
AND DO THEM BY YOURSELF AND IN YOUR OWN
WAY. THERES NO SUBSTITUTE FOR YOUR OWN WAY
OF THINKING AND YOUR IMAGINATION. IF YOU
FORGET SOMETHING,
GO TO THE BOOK!!
23
Slow response fibers are those found normally in
the Sinoatrial Node and the Atrioventricular Node.
Nonetheless a fast fiber can transform into a slow
one if appropriate conditions are present. The main
characteristics of the slow fiber action potential
are; a slower phase 0 in which Ca++ becomes an
important component of the depolarizing
current, no phase 1 and very little or absent phase
2. A very important aspect is that the Relative
Refractory Period or RRP extends into phase
4. This means that the fiber will not respond with a
full amplitude action potential until it is well into
phase 4. This makes the fiber less responsive for
sometime even when it is in phase 4 and creates a
period of extended refractoriness. As you will see
this has major implications for the type of
electrophysiological activity in which these fibers
are involved.
24
Local currents between polarized and depolarized
zones (or cells) control the conduction of the action
potential in cardiac fibers. Another very important
factor is the presence of gap junctions between
cells. These junctions create an electrical coupling
among all the fibers and greatly promote
conduction. Remember that in the cell local current
refers to the movement of ions. Thus in the two
fibers above you can see a current of positive ions
moving across the gap junctions from fiber A to B
intracellularly and depolarizing fiber B. At the same
time a reverse current of positive ions is moving
extracellularly from fiber B to A. The original
depolarization in A was caused by an action
potential that originated in this fiber or an adjacent
one. Remember that action potentials spread out in
all directions across the surface of the cell. Its like
throwing a stone in a puddle and looking at the
propagation of the waves in the water.

25
The conduction of the action potential depends on
the same factors for both slow and fast fibers. The
difference in conduction velocities that we observe
among these fibers is due to the differences in their
respective action potentials. For example, the
action potential of the fast fiber is higher in
amplitude (height of depolarization wave), it has a
fast rate of depolarization (Na++ enters very fast)
and the depolarization starts from a very negative
Em (ie -80mv). This means that the change that
occurs in the depolarization site is BIG. Thus, the
effect that it will have on adjacent sites will also be
BIG (ie big local currents will be generated). The
slow fiber conducts differently because the
amplitude is lower, the rate of depolarization is
slower and it starts depolarizing from a less
negative Em.
26
The figure above shows the effect of high
extracellular K+ on the action potential of the fast
fiber. As you can see the fast fiber action potential
is transformed into a slow fiber action potential by
the high K+. The clinical implications are extremely
important. Low blood flow to an area of the
heart as in coronary disease diminishes the
activity of the Na+/K+ ATPase in the heart
cells of the area. As a result K+ tends to
accumulate in the extracellular fluid bringing about
the changes observed above. The transformation of
the fast fibers into slow ones results in a reduction
of the conduction through the affected region
causing conduction blocks that can produce serious
alterations in cardiac rhytmicity. Some of the
affected cells may also become an ectopic focus
generating an aberrant cardiac rhythm and
interfering with the action of the normal cardiac
pacemaker. (pages 25-26 B&L)
27
The main reason why high extracellular K+
transforms a fast fiber into a slow one is easy to
understand. Remember the h gates for Na+? (if
not, review quickly!). As the Em of the fast fiber
is lowered by the effect of high extracellular K+ (do
you know why this happens?), h gates in the
membrane are gradually closed. As a result when
the cell depolarizes less Na+ channels are
activated. At a very high extracellular K+ level
most of the h gates are closed and Na+ becomes a
minor player in the depolarization phase of the
action potential. The major player now is Ca++
that enters the cell more slowly (see phase 0 of the
slow fiber AP). Now you can understand why high
levels of K+ in plasma are so dangerous to the

heart. Go and look for the ranges of K+ that the

body can tolerate. As you can see the clinical
correlation of this basic science concept is very
important.
28
One of the main electrophysiological differences
between fast and slow fibers is the duration of their
respective Relative Refractory Periods or RRPs.
In the fast fiber all the fast Na+ channels are totally
recovered at the end of phase 3. In the slow fibers
this recovery is not as fast and we can see the RRP
extending into phase 4. This means that during
phase 4 there is a period in which the fiber cannot
be fully stimulated. It conducts more slowly during
this period and is more prone to conduction blocks.
This period of prolongued refractoriness is the POST
REPOLARIZATION REFRACTORINESS.
29
The figure above shows the Absolute Refractory
Period (ARP) and Relative Refractory Period
(RRP) for a fast fiber. As you can see there is no
Post Repolarization Refractoriness in fast fibers.
Right at the beginning of phase 4 you can elicit a
full blown action potential. All the sodium gates are
fully recuperated at this time. If we stimulate
during the early RRP, the AP elicited is similar to a
slow fiber AP. Do you know why? Think about what
happens to the h gates at the membrane potential
of the early RRP. Remember the effect of high K+
on the h gates.
30
The figure above shows a slow fiber action
potential and the effects of Post
Repolarization Refractoriness(PRR). Theres a
200msec delay from the onset of phase 4 to the
time in which the fiber will respond again with a
complete AP similar to the preceding one in
amplitude. A and B are responses elicited by
stimulation during the period of PRR.
It is clear that during this period the fiber will
respond with less than maximun capacity and
conduction of these responses will be slower than
that of a full response. See page 27 B&L.
31
Even a denervated and isolated heart kept in
appropriate conditions continues to beat with a
regular rhythm. The heart shows automaticity
and rythmicity as intrinsic characteristics. The
main area that regulates the frequency of the
heartbeat is the Sinoatrial Node. It beats at a
higher frequency than any other area. If the SA

node is damaged by an infarct in that area, then

the Atrioventricular Node (AV) takes over until
eventually the atrial cells develop another
pacemaker. In addition there is a safeguard system
formed by the idioventricular pacemakers (Ips)
that are capable of firing at a reduced rate of 30 to
40 beats per minute. The Ips are really
ventricular conduction fibers that take the role of
pacemakers. This usually happens when the AV
node cannot conduct the impulse coming from the
SA node to the ventricles. See pages 28,29 B&L.
32
The figure shows a typical pacemaker cell action
potential. The main characteristics that you can see
are: the absence of any significant resting potential
(In fact, the resting potential is really the very short
period of time that the fiber remains in the
minimum repolarization potential), and a period in
which the cell depolarizes automatically or
pacemaker potential period. During this time
there is a slow depolarization that gradually
brings the cell to a threshold potential beyond
which an action potential occurs. In reality the
pacemaker potential is happening during phase 4
of the action potential. So instead of having a
quiescent phase 4 with a constant membrane
potential what we have in these cells is a
continuous depolarization during this period that
brings the cell to the threshold. It is easy to see
that if the slope of the pacemaker potential is
changed, the firing frequency of the cell is also
altered. See pages 29-30 B&L.
33
The effects of alterations in the slope of the
pacemaker potential are clearly shown in the figure
above. If we take curve b as that showing the
normal baseline response, then curve a clearly
shows the effect of catecholamines like epinephrine
and norepinephrine and curve c shows the effect of
acetylcholine. Catecholamines are released during
exercise and increase the heart rate. Acetylcholine
is released by cholinergic (vagal) innervation of the
heart and reduces the heart rate. It is interesting to
note here that in the denervated heart of
transplant patients the heartbeat frequency is
above the norm. It may be even 100BPMs at rest
compared to a normal of 70BPMs for an innervated
heart. In terms of regulating the heartbeat at rest
then what system predominates, the cholinergic or
the adrenergic? As you can see the pacemaker
potential has very important clinical
implications.
34

The genesis of the pacemaker potential (PaP)

invloves three ionic currents. During the early
period of the PaP a small Na+ (If) current starts to
depolarize the cell. This current is followed by a
large inward Ca++(iCa) current that eventually
brings the membrane potential to the threshold
and is also the main current carrying the positive
charge inside the cell during the depolarization
phase. The K+ current is lower during the
pacemaker potential phase but increases
dramatically at the peak of the depolarization
phase and is the main current involved in bringing
the cell membrane potential back to the minimum
repolarization potential.
35
As you can see in the figure this is the result of the
depolarization in the pacemaker cell. At the end of
the depolarization period the main current is K+.
Catecholamines like epinephrine and
norepinephrine act by increasing all the three
currents involved in the pacemaker action
potential. Cholinergic stimulation via the release of
acetylcholine brings about a depression of the if
and iCa currents and increased K+ current. The
increase in the K+ current is mediated by specific
receptor operated K+ channels that open in
response to acetylcholine and hyperpolarize the
cell. At this point you should be able to explain the
changes in slope of the pacemaker potential in
response to catecholamines or acetylcholine and
consequently the changes in rhythm induced by
these agents. If you cannot do this please review
this complete session. See the next figure.

frequency depolarizes adjacent cells by allowing

Na+ to enter more frequently. Eventually the
Na+/K+ ATPase is activated by the increased level
of cytoplasmic Na++ created by the repeated rapid
firing. Since the Na+/K+ ATPase is electrogenic and
extrudes more Na+ in exchange for K+, this
activation induces cell membrane hyperpolarization
and increases the time required for depolarization
thus suppressing automaticity in adjacent cells. In a
clinical correlate, an ectopic focus induced by
coronary artery disease can fire at a frequency
which is much higher than that of the SA node. It
becomes the new heart pacemaker by producing
overdrive suppression over the SA node. In
addition, if the ectopic focus suddenly stops firing,
the SA node may be left momentarily suppressed
causing the heart to stop and inducing syncope.
39

The figure above is a complete review of the basis

for the pacemaker potential. The figure on top
shows a pacemaker cell action potential and the
figure below shows the ionic currents involved
during the same period of time.

The conduction system of the heart is formed by

cardiac myocites that have been modified mainly
for conduction purposes and not for
contraction. The conduction system originates in
the right atrium with the SA node. Fibers called
Bachmanns Bundle conduct from the right to the
left atrium. Posterior internodal pathways conduct
from the SA to the AV node. The AV node derives
into the Bundle of His from which the Left(LBB) and
Right (RBB)Bundle Branches originate
subendocardially. The RBB is basically a
continuation of the His bundle. The LBB arises
perpendicular to the RBB and divides in the left
subendocardial surface into the anterior and
posterior divisions. The bundle branches subdivide
into a conducting network of Purkinje Fibers that
ramify in the subendocardial spaces. Notice the
direction of the ramifications. This is the direction
that the cardiac stimulus will take and will
determine the form of the electrocardiograph
waves. Infarcts can disrupt the conduction and
alter the electrocardiogram.

37

40

Addition of Ltype Ca++ channel antagonists like

Nifedipine lowers the amplitude of the pacemaker
cell AP and also lowers the slope of the pacemaker
potential reducing the firing frequency. A similar
effect is observed under low levels of extracellular
calcium. This demonstrates that the Ca++ current
is a major factor in the generation of the
pacemaker cell automaticity and rythmicity.

The schematic representation above shows the

conduction pathways in the heart. Of particular
interest is the AV node pathway in which the
stimulus must transverse three regions. The N
region is one of slow conduction and is a
significant factor in the important process of
NODAL DELAY. The round cells in this region are
particularly slow conductors.

38

41

Overdrive Suppression explains why the area of the

heart that fires with the greatest frequency is the
one that regulates the heart beat. A greater firing

The concept of NODAL DELAY not only involves

the slow conductors of the N region in the AV node
but also the NA region where although conduction

36

is rather fast the stimulus must transverse a longer

path. As the stimulus approaches the N region it is
slowed by the appearance of more round cells until
the stimulus finds itself in the N region . As the
stimulus leaves the N region it begins to find more
and more His Bundle fibers which are fast. The
conduction velocity then increases and becomes
again very fast. NODAL DELAY has important
clinical implications. It can be extended by
conditions that increase the conduction time
through the AV node and can be visualized in the
electrocardiographic recording as an increase in the
P-R interval.
42
The figure above is a representation of a macro or
micro conduction pathway in the heart. It illustrates
conduction blocks and reentry. B shows what
happens when a stimulus is blocked in only one
direction by conduction tissue that has died. In C
the stimulus can continue down the conduction
pathway using an alternate bypass route.
Nonetheless it is blocked in two directions. In D the
stimulus can also follow the alternate route but
finds an area where the conduction tissue is not
dead but merely ischemic. The lack of oxygen has
increased extracellular K+ in the area and this
tissue is conducting slowly. This allows the stimulus
to slowly trascend the area and enter the pathway
in a retrograde direction. Notice that it can not
move in an antegrade direction.The fact is that the
stimulus moves so slow over the ischemic area that
it allows the conduction tissue above to recuperate.
This creates the reentry that can cause a disruption
in the normal heart rhythm.
43
Why are these re-entry circuits so important that
Im required to learn them even when I think that
they have nothing to do with the clinics? Well
they are the fundamental in the pathology of
Arrythmias. Suppose the figure to the left is the
normal circuit. Everyone has two conducting
pathways, a fast pathway and a slow pathway.
Primarily the action potential is propagated
first through the fast pathway, due to the
quickness of depolarization of the myocardial fibers
in that area. Thus the AP that traverses the fast
pathway will quickly traverse the rest of the
myocardium and make it unexcitable. This is why
the current through the slow fiber (blue arrow)
stops and cant continue through the tissue
(redline). Now, on the figure to the right, suppose
that you have an ischemic area of tissue (red star).
This will not allow the action potential through the
fast fiber to traverse through that tissue, thus in

this scenario, the conducting pathway will be the

slow pathway. Conduction will thus be slower, but
the heart will still be able to conduct. The problem
is that if the current finds an opening (a set of
myocardial fibers in the ischemic tissue that are
depolarizable) it will find its way upward again
through the circuit (blue arrow). This will again
depolarize the myocardial tissue and lead to a reentry loop. So, what's wrong with a re-enrty loop??
Well, think that this new re-entry current will cause
more depolarizations in the ventricular tissue. Thus
the ventricles will depolarize more times than it
should. This will create an ectopic pacemaker,
since it depolarizes much faster that the SA node.
This new pacemaker will become the new
pacemaker of the heart and lead to Paroxysmal
Supraventricular Tachycardia.
44
You should know at least the three basic conduction
blocks shown above. In First Degree AV block
conduction through the AV node is delayed and the
electrocardiogram shows a P-R interval greater
than .20 As you can imagine, the N cell region has
a lot to do with this. N cells show repolarization
refractoriness which means that any stimulus
falling in the PRR period of the cells will not be
conducted. So, if the SA node fires at a very high
frequency, conduction in the AV node is slowed. In
a way this means that the AV node acts as a filter
not allowing certain frequencies from going to the
ventricles. In Second Degree AV block the
frequency of atrial firing is so high that only half of
the atrial stimuli make it through the AV node. In
Third Degree AV Block there may be sufficient
vagal stimulation to completely block conduction
through the AV node.
45
The fast conductors of the ventricular areas are the
large Purkinje fibers. These are specialized
cardiac cells much larger than myocytes. Their
diameter coupled to surface membrane
specializations like lack of T tubules allows them to
conduct very rapidly. Purkinje fibers also have a
long Absolute Refractory Period (ARP). This means
that for a long period of time the cell is refractory
to any new stimulus. It simply will not respond
during this time. The slower the heart rate, the
longer the ARPs of these cells. Thus, if a premature
atrial impulse is produced at slow heart rates, even
if it passes the AV node, the atrial impulse will
probably fall into the ARP of the Purkinje fiber. It will
not be able to stimulate the ventricles keeping the
cardiac rhythm in check. At a high frequency of
atrial impulses the AV node protects against

premature atrial depolarizations. Review the action

of the AV node. See pages 38-39 in the B&L.

At the end of this section you should be able to:

words, at this initial myocardial fiber length the

heart contracts with maximum force and generates
the greatest pressure. This is the length tension
relationship for the heart muscle and it has major
clinical implications.

1. Explain the Frank-Starling relation.

49

2. Understand the concept of preload and afterload

in the heart

A preloaded muscle is one in which some tension

has been applied before the muscle performs any
work. In the case of the heart this tension is
provided by the End Diastolic Volume (EDV).
Afterload refers to the load that the preloaded
muscle has to work against. In the heart it refers to
the aortic pressure present just at the instant that
the aortic valve opens. Thus, the higher the aortic
diastolic pressure, the more work the heart has to
perform to pump blood into it. A higher aortic
pressure means more afterload. Afterload is also
defined as the Ventricular Wall Stress that develops
during systolic ejection. It can be estimated using
Laplaces Law:

47

3. Understand the concept of contractility and

positive/ negative inotropism.
4. Recognize a ventricular function curve and the
effects of heart failure and exercise in the curve.
5. Understand the dP/dt as an index of contractility.
6. Be able to explain the events in the cardiac cycle
in terms of changes in pressure, flow and volume in
the ventricle, aorta, atria and veins.
7. Understand the left ventricular Pressure/Volume
loop.
8. Recognize the effects of preload, afterload and
contractility in the P/V loop.
9. Understand the measurement of cardiac output
using the Fick Principle.

VWS = Pressure x radius / 2 (wall thickness)

The pressure can be estimated from arterial
systolic pressure. In heart failure the dilated heart
increases its thickness to reduce wall stress. This is
a compensatory measure.

48
The relationship above was studied more than 100
years ago by Drs. Frank and Starling in the UK. It is
a classical study in cardiovascular physiology and
the concept, called Starlings Law of the Heart, still
stands today though much better understood. Now,
read your axes carefully. The x axis shows either
the volume of blood in the left ventricle at the end
of diastole when the ventricle is full. At this point
the cardiac myocites are stretched to a certain
length so we can also place in this axis the initial
myocardial fiber length. Either one will do. The Y
axis depicts ventricular pressure. This is the
pressure generated by the contraction of the
ventricle(upper curve) or by the mere presence of a
volume in the ventricle(lower curve). This pressure
is, at the same time, a measure of contractile
force(upper curve). Now, look at the lower curve
again. It shows the pressure inside the ventricle as
a function of either initial fiber length or end
diastolic volume. This is a passive pressure
generated by the volume inside a ventricle that is
not contracting. The upper curve shows what
happens when the ventricle contracts at different
levels of end diastolic volume (EDV). As you can
see, there is a specific EDV at which the ventricular
pressure generated is maximal. This EDV
corresponds to a certain initial fiber length. In other

50
As the afterload of the heart is increased under a
constant preload more and more ventricular
pressure is generated until a maximum is reached.
At this maximum level of afterload the aortic valve
is not capable of opening , the ventricle is
contracting isometrically and no work is being
performed. Peak isometric force has been attained
for a particular value of preload. If the preload is
increased then the left ventricular pressure
developed at all points will increase and the new
curve will be parallel and on top of the original one.
Peak isometric force will be reached at a higher
level and a change in peak isometric force versus
initial fiber length (preload) will have occurred.
This is not a change in contractility.The
afterload has been increased by raising aortic
pressure. By reducing the blood runoff from the
arterial tree to the capillaries you can increase the
volume of blood left in the arteries and by
consequence the arterial pressure. Arteriolar
contraction can induce this effect which is also
clinically correlated to essential hypertension. As
you can see, in hypertension the heart muscle
works harder to pump the same amount of blood
against a high afterload. In time this process

deteriorates the heart muscle and leads to heart

failure.
51

closely follows the same changes as the left atrial

pressure curve shown here. It is of paramount
importance that you come to class prepared
to discuss the cardiac cycle.

The graph above illustrates the important concept

of contractility. Contractility is defined
experimentally as change in peak isometric
force vs. initial fiber length (represented by end
diastolic volume). We can see that the normal heart
above exhibits a certain degree of contractility and
peak isometric force. Stimulation by
Norepinephrine or Epinephrine as occurs during
exercise raises the level of cardiac contractility. On
the other hand, a failing heart (lower curve) has a
reduced contractility that impairs its normal
function. In addition it works with a higher preload
due to a reduced ventricular ejection and high
blood volume due to fluid retention. A drug like the
Na++ pump inhibitor digitalis increases the
contractility of the failing heart by increasing Ca++
levels inside the cardiac myocites. It is a drug of
choice for heart failure. The curves above are
called ventricular function curves and you will
continue to see them through this section. See
pages 65-67 B&L

55

52

56

Another good index of contractility is the change in

left ventricular pressure over time shown above.
Curve A belongs to a normal heart. B is a heart with
higher contractility like our Epinephrine stimulated
heart. C is a heart with a lower contractility like our
failing heart. As you can see the instant change in
ventricular pressure per instantaneous change in
time is much higher for B. The dP/dt or change in
pressure over time becomes then an index of
cardiac contractility.

The pressure volume loop for the left ventricle

illustrates the changes in ventricular pressure as
the volume of the ventricle varies during a full
cardiac cycle. The area under the loop is a measure
of the work performed by the ventricle. At C we
start with a full ventricle that has begun to
contract. The C-D interval shows no change in
volume but a steep rise in pressure (isovolumic
contraction). The interval D-E shows a rapid
reduction in volume with some contraction (rapid
ejection phase). E-F is a period of slower volume
reduction and start of relaxation (slow ejection
phase). F is the point of closure of the aortic valve
and F-A is another interval where volume doesnt
change but pressure is reduced significantly
(isovolumic relaxation). At A the mitral valve opens
and rapid filling begins followed by B-C where a
slower filling occurs. At C the mitral valve closes
and we go back to C-D. See page 77 in B&L.

53
The coordinated contraction-relaxation of the atria
and ventricles of the heart make up the complete
cardiac cycle seen above in graphic detail. Coming
from the top of the graph you can see that basically
this is a compound graph formed by several
individual graphs in which the x axis is always time.
The vertical lines separate time intervals. At the
very bottom of the graph heart sounds and the
electrocardiogram are illustrated in coordination
with all the other events of the cycle. This cycle is
based on events happening in the left heart. The
upper 3 curves show the changes in atrial,
ventricular and aortic pressures during the cycle.
The lower curve shows the changes in ventricular
volume and the middle curve shows the changes in
aortic blood flow. In your book (page69) you will
also find the venous pulse curve. This curve

Look how important it is to understand the Cardiac

Cycle!!! The figure to the left is what normally
happens during ventricular contraction. When the
ventricle contracts, the pressure in the ventricle
rises. Remember it must rise above 80mmHg in
order to counteract the normal aortic afterload and
open the aortic valve. When it reaches this point,
the aortic valve opens and the pressure in the aorta
will rise concomitantly with the ventricular
pressure, as you can see in the figure. However if
there is aortic stenosis, the aortic valve is very hard
ad it very difficult to open. Thus, when the
ventricle contracts it exerts pressure on the aortic
valve since the valve does not open correctly,
blood is not efficiently expelled into the aortic arch,
and thus the aortic pressure will not rise
concomitantly with the ventricular pressure (Figure
to the right). This is primarily how you would
Diagnose aortic stenosis!

57
If the afterload and contractility are left constant
but preload is increased ( as when you administer
intravenous fluids), the left ventricular End
Diastolic Volume (EDV) will rise. The stroke volume
will increase by the Frank- Starling mechanism and
the ESV achieved will be the same as that observed
prior to the increase in preload. This means that as
long as contractility and afterload remain constant

the left ventricle can adjust its stroke volume and

effectively empty its contents to match its diastolic
filling volume. A hypertrophied ventricle becomes
stiffer than a normal one. This changes the slope of
the diastolic filling curve and makes it steeper. The
ability of the cham,ber to fill is reduced resulting in
a lower than normal EDV. If afterload and
contractility remain constant, then the stroke
volume is reduced.
58
If the preload and contractility are kept constant
but afterload is increased ( as in hypertension or
aortic stenosis), then the pressure generated by
the left ventricle increases. More ventricular work is
used to overcome the resistance to ejection and
less fiber shortening takes place. Thus, an increase
in afterload results in a higher left ventricular
systolic pressure and a greater than normal left
ventricular ESV. In this situation the ventricular
stroke volume (EDV-ESV) is reduced. The relation
between ESV and afterload is linear as shown
above for the End Systolic Pressure Volume
Relation or ESPVR.
59
The slope of the ESPVR line is a measure of cardiac
contractility and analogous to the active tension
curve of the hearts length-tension relationship
(Frank-Starling). An increase in contractility ( as will
happen with an infusion of epinephrine to treat
asthma) increments the slope of the ESPVR from 1
to 2. At this new level the ventricle empties more
completely regardless of the given preload or
afterload. The stroke volume is higher. The ESV
decreases. In conditions were contractility is
reduced like high dose B blocker therapy or dilated
cardiomyopathy associated to cardiac failure, the
ESPVR slope is reduced. From the last two figures
two things must be realized. First, the ESV is
dependent on the afterload and contractility.
Second, the ESV is independent of the EDV.
61
In the Fick Principle for measuring cardiac output
we just apply the law of conservation of mass. In
other words, the oxygen that we find in the
pulmonary veins(PvO2) must be a sum of the
oxygen that came from the air in the alveoli plus
the oxygen that was already in the blood when it
arrived at the pulmonary capillaries(PaO2) from the
pulmonary arteries. Looking carefully at the
diagram above you can see that the difference in
concentration of oxygen between the Pa and Pv is .
05mlO2/ml blood. You can also see that in one
minute 250ml of oxygen were taken up by the

pulmonary capillaries. So the question is; How

much blood had to traverse the pulmonary
capillaries in one minute in order to pick up 250ml
of oxygen? Since you know that each ml of blood in
the Pv contains .05 ml O2 more than the blood in
Pa, then dividing the Oxygen consumption per
minute by the O2 pulmonary arteriovenous
difference gives you the answer. In other words
5000mls of blood had to traverse the pulmonary
capillaries in one minute in order to pick up 250mls
of oxygen. Since for practical purposes the
complete output of the right heart passes through
the pulmonary capillaries, you have a measure of
that output per minute and thats your cardiac
output.
62
At the end of this section you should:
1. Be able to recognize the concepts of velocity,
flow and static and dynamic pressure.
2. Explain the clinical implication of lateral versus
dynamic pressure.
3. Explain the effects of vessel diameter on velocity
of flow.
4. Be able to explain the Poiseuille equation.
5. Describe the effect of series and parallel vessels
in the resistance to blood flow.
6. Explain the concept of the Reynolds # and its
clinical implications.
63
The three concepts illustrated above are usually
well forgotten by now but must be brought back
from our neural hard-disc . First is velocity (V)
which is what distance(D) is traveled in a certain
amount of time(T) like miles/hr or miles/sec or
cm/sec. Flow(Q) is the volume movement per unit
of time like ml/min or liters/min. Flow and velocity
are related so that velocity is directly proportional
to flow (Q) and indirectly proportional to cross
sectional area (A). If you dont have these concepts
clear then review them in the old physics book from
college. See pages 115-116 B&L.
64
Using the example from your cardiovascular book.
If we keep a constant flow of 10ml/sec for a fluid
moving through ducts of different cross sectional
areas , then velocity must change accordingly.
Logically less velocity is required to move the same
volume in the same amount of time through a
larger cross sectional area than through a smaller

cross sectional area. Use the common water hose

as an example. If you consider that the pressure of
water coming from the faucet remains constant,
then the flow also remains constant. If you lost the
piston that regulates the water output at the end of
the hose, the water coming out will do so at a slow
velocity. You cannot use it to wash the car or push
leaves out of the marquesina. The common solution
is to place your finger over the end of the hose
reducing the diameter and cross-sectional area at
that point. Now the water comes out at a greater
velocity and you can push the leaves out. The
velocity has increased but the flow remains the
same. See page 116 B&L.

component of pressure. Notice that the total

pressure never changes with changes in diameter.
The lateral pressure on the contrary is reduced in
the small diameter vessel. What happens here is
that as the velocity increases in this vessel it does
so at the expense of lateral pressure which is
reduced. Imagine that this duct represents a
coronary vessel with an atherosclerotic plaque
reducing its diameter. If at the point where the
atherosclerotic plaque reduces the diameter
another branch originates. What will happen to
blood flow through that branch? Can you see the
clinical implication? See B&L 116-117 What
happens with aortic stenosis?

65

68

Hydrostatic pressure is an important concept that

we should master in order to better understand the
dynamics of fluids like blood. Due to its weight,
density and height the column of water above
induces a pressure against the walls of the closed L
tube. This is a static pressure since the water is not
moving. If we place a piston over the open end of
the L tube and push it, the pressure will increase
accordingly but will still be static or hydrostatic
pressure. We increased the pressure but did not
move the water. All the energy in this system is
stored as potential energy.

The Poiseuille equation above summarizes the

main factors that affect flow through a conduit
system. One of the major factors is the radius of
the cylinder. A small change in radius will produce a
very large change in flow. The other major factor is
the pressure difference between the influx and
outflow sites. Cylinder length and fluid viscosity are
inversely related to flow. In our circulatory system
the maintenance of a constant flow is imperative in
order to provide the necessary tissue perfusion.
The maintenance of the pressure gradient that
provides this flow is a major function of the HeartVessels working together as a coupled unit. See
B&L 120-121.

66
When a fluid is at rest as in the last example, the
total energy of the system is potential energy but
when we put the fluid in motion part of the
potential energy is converted to kinetic energy.
Thus when in our last example the fluid was static,
the pressure over the walls at the bottom was
about 100mm Hg. Now as the fluid acquires
movement, as we will see in the next example, the
lateral pressure over the walls is reduced by a
certain amount. That amount has now been
converted to hydrodynamic pressure. For a fluid in
motion then, there is a static and dynamic
component of pressure.
67
The drawing shows the reduction in static (lateral)
pressure caused by the movement of water as we
open up the bottom of the L chamber. This concept
has major clinical implications. If you look at the
insert there is a tube of different diameters through
which a fluid is moving at a constant flow. The
perpendicular tubes are measuring two things. The
L tubes measure the lateral or static component of
pressure plus the linear or dynamic component of
pressure. They measure total pressure. The
straight tubes measure only the lateral

69
In your old college physics course the professor
taught how electrical resistance works when
several resistors are placed in parallel or series
conformation. The same applies to the circulatory
system as illustrated above. Now, in our arterial
system the resistance from the aorta to the
arterioles increases. Even though the arteries
subdivide into smaller numerous vessels as we
reach the arteriolar level the subdivisions are not
enough to increase the cross sectional area to the
point were resistance begins to fall. So as blood
flows from the aorta to the arterioles it encounters
a higher resistance on its way. After the arterioles
the subdivision into so many capillaries brings the
cross-sectional area beyond the critical point after
which the resistance falls effectively providing for a
lower velocity in an area were exchange between
the capillaries and interstitial space takes place.
See pgs. 124-125 B&L
70
Laminar fluid flow refers to a profile where the
velocity of flow near the surface of the cylinder is
zero and maximal in the center of the cylinder. This

type of flow is very effective and requires less

energy. If irregular currents occur in the fluid then
turbulent flow develops and more work is required
to move the fluid. The heart works much easier
against a laminar rather than a turbulent flow. The
Reynolds number predicts the fluid turbulence. It is
a dimensionless quantity. Diseases such as anemia
tend to reduce the viscosity of blood. From the
equation above you can see that this will bring
about and increase in the Nr and more turbulent
flow. Sometimes this factor will create murmurs in
the heart due to blood passing a narrowed or
stenotic valve or a narrowed vessel. The Korotov
sounds heard during auscultation in blood pressure
measurement are due to turbulent flow in the
brachial artery created by the narrowing artificially
produced by the blood pressure cuff. See page 126
B&L.
73
At the end of this session you should be able to:
1. Understand how the arterial system works as a
hydraulic filter.
2. Understand the concepts of compliance and
elastance and how they apply to the arterial
system.
3. Understand pulse pressure and how it is affected
by stroke volume, increments in peripheral
resistance and changes in compliance.
4. Read and understand the stroke volume vs.
pressure relations.
74
The more compliant aorta (top) is able to
accommodate more volume with less changes in
pressure. The distensibility also promotes a more
continuous and less intermittent blood flow since
the energy stored as the organ is distended is
expended to keep the blood flowing during diastole.
The more rigid and less distensible aorta (bottom)
is not able to easily accommodate the volume of
blood pumped by the left heart. Pressure inside the
aorta during systole increases rapidly. In diastole
the rigid aorta tends to produce a more
intermittent flow due to its inability to maintain a
continuous blood flow by using potential energy
stored in distension. This is of course an extreme
condition since the aorta even in older persons
retains some degree of compliance. See B&L page
136.
75
The graph above clearly shows that if the aorta is
substituted by a rigid plastic tube, the heart must

work harder to pump the blood. Theres an overall

increase in the heart oxygen consumption. Thus, as
we get older and our aortas get less compliant our
heart must work harder to pump blood.
Nonetheless our aortas will not get as hard as
plastic so some degree of distensibility remains.
See page 139 B&L.
76
The classic experiment shown above was done with
human aortas obtained post-mortem. Each aortic
segment was filled with fluid at the same time that
the increase in pressure was being monitored. As
you can see young aortas are capable of
accommodating larger volumes with smaller
increments in pressure. They are more compliant.
The slopes of these curves gives us an idea of the
changes in pressure vs. changes in volume or
dV/dP. The dV/dP is the compliance of the vessel
and as age increases dV/dP decreases.
77
The elastic modulus is a measure of rigidity and
inversely proportional to compliance. It is measured
by the change in pressure versus the fractional
change Da/Db in aortic diameter or the diameter
of any other compliant vessel. Its just another way
of looking at distensibility in a vessel.
78
The figure above shows how changes in MAP occur
with changes in cardiac output (Qh) or changes in
peripheral resistance(R). The figures in the top
show what happens when the cardiac output or
peripheral resistance increase instantaneously. The
figures in the bottom show how the system arrives
at e steady state with the new MAP. In the cardiac
output side you can see that as the Qh increases
more volume enters the aorta so pressure inside
the vessel increases. Initially Qh is double the
peripheral outflow (Qr). As the MAP increases Qr is
raised until it reaches the same value as Qh and a
steady state is reached. In the peripheral
resistance side basically a similar thing happens. If
we raise R and lower Qr to half of what it was
initially then more blood will remain in the aorta.
Since we have not changed Qh more blood will
continue to enter the aorta until the MAP is raised
to such levels that Qr increases to its original value.
It is interesting to note here that in essential
hypertension R is increased but CO remains the
same. As a result MAP increases and Qr eventually
reaches the same value that it originally had. Thus
tissue perfusion is maintained at the expense of a
raised MAP. See page 143 B&L.

79
The important concept here is to notice that MAP is
directly proportional to the difference between
inflow into the arterial system or Qh (given by CO)
minus outflow from the arterial system or Qr (given
by peripheral resistance) and indirectly proportional
to compliance. If we consider that at any given age
range compliance will remain rather constant, then
the major factors regulating MAP will be the cardiac
output (CO) and the peripheral resistance (R).
Remember that the main regulator of peripheral
resistance are the arterioles. Cardiac output and
peripheral resistance are factors that can be
neurally regulated. Compliance on the other hand
is an intrinsic property of the arterial system and
will be mainly dependent on age.
80
The arterial pulse pressure is the difference
between systolic and diastolic blood pressures. It is
also a function of stroke volume and arterial
compliance. If we consider compliance as constant
then the relation between arterial volume and
pressure during systole and diastole can be
graphically depicted as seen above. Notice that the
line intersecting each volume vs. pressure points
depicts the compliance (dV/dP). V1 and P1 show
the arterial volume and pressure during diastole.
V2 and P2 show the same values during systole. VA
shows a volume of blood that corresponds to the
mean arterial pressure or PA. The pulse pressure is
the difference between P2 and P1. This change in
pressure is a function of the observed volume
increment (V2-V1) and 80% of this volume
increment is a large fraction of the stroke volume. If
stroke volume doubles then P3 becomes the new
level of diastolic pressure and P4 the new level of
systolic pressure with PB as the new mean arterial
pressure. The corresponding volumes are V3, V4
and VB. This increment in stroke volume takes into
account that no changes occurred in heart rate or
peripheral resistance. See B&L pages 145 to 149.
81
As you can see changes in compliance increase the
pulse pressure while changes in total peripheral
resistance (TPR) will induce little change in the
pulse pressure if the compliance remains constant
but larger changes in the pulse pressure if the
compliance is higher. Remember that when total
peripheral resistance increases the volume of blood
in the arterial system increases and blood pressure
is increased. The stroke volume has remained the
same but the pulse pressure has moved to higher
levels due to the higher arterial volumes. In fact
the mean arterial pressure is also higher. Diastolic

and systolic pressures are higher. In the graph

above B represents a more common clinical
situation in which an older individual suffers from
hypertension.
82
At the end of this session you should be able to:
1. Draw and interpret a vascular function curve.
2. Draw and interpret a cardiac function curve.
3. Recognize the effects of changes in volume,
contractility or peripheral resistance in the vascular
and cardiac function curves.
4. Understand the effects of cardiac failure in the
vascular and cardiac function curves.
4. Be able to explain the significance of the
coupling that exists between the heart and blood
vessels using the example of the arrested heart.
83
The graph above shows the dependence of central
venous pressure(CVP) on cardiac output. In other
words, how changes in cardiac output induce
alterations in CVP.This is the VASCULAR FUNCTION
CURVE. CVP is the pressure measured at the right
atrium. The above curve shows that as cardiac
output increases CVP decreases. With the heart in
complete arrest the venous pressure becomes the
mean circulatory pressure or Pmc. At normal levels
of cardiac output (5L/min) the central venous
pressure has values around 2mm Hg. See B&L
Chapter 9.
84
Changes in total blood volume shift the vascular
function curve to the right or left. A transfusion for
example increases the Pmc. Thus at the same level
of cardiac output there is less reduction in the CVP.
The reverse happens with loss of volume as in
hemorrhage. An increase in venomotor tone
(contraction of the veins) will produce the same
effect as a transfusion while a decrease in
venomotor tone will produce a hemorrhage like
effect on the vascular function curve. Make sure
you understand this!
85
Changes in TPR or total peripheral resistance do
not cause great variations in the Pmc. This is due to
the fact that the arterioles contain only a small
percentage of the circulating blood. Vasodilation
will bring more blood into the venous side so ,at a
given cardiac output, the CVP will be increased. In
vasoconstriction less blood reaches the venous side

so at a given cardiac output CVP is decreased. As

the cardiac output decreases to extremely low
levels notice that the changes in CVP due to either
vasodilation or vasoconstriction are reduced.
Remember that changes in peripheral
resistance refer only to changes in arteriolar
diameter!
86
Before anything else please notice that in the
graph above we have taken the Vascular Function
Curve graph and positioned it so the the cardiac
output now becomes the Y axis and the CVP
becomes the X axis. Now, over the vascular
function curve we have drawn a new curve that
reflects how CVP alters cardiac output. This new
curve is the CARDIAC FUNCTION CURVE and is
basically an expression of the Frank-Starling
mechanism. It shows that an increment in CVP will
bring an increment in cardiac output. If CVP
increases more blood returns to the heart, end
diastolic volume increases and contractile force
increases (Starling).
87
Sympathetic stimulation of the heart will induce an
upward shift of the cardiac function curve. Cardiac
output will be higher and CVP will be gradually
reduced until a new equilibrium level is reached at
point D. Notice that initially the sudden increase in
cardiac output does not change CVP. CVP is
reduced gradually from B to D but remains lower
than normal and at a higher cardiac output. Notice
also that as CVP is reduced so is cardiac output.
88
Changes in blood volume affect cardiac output and
CVP. An increase in volume increases both CVP and
cardiac output as shown above. Increments in
peripheral resistance decrease cardiac output but
produce small changes in CVP even though the
vascular function curve is also shifted downward.
The cardiac function curve is shifted downward
because of an increase in afterload produced by
the increment in peripheral resistance.
89
Shown above are the effects of severe and mild
cardiac failure in both the vascular and cardiac
function curves. In severe heart failure a
combination of low cardiac output and high blood
volume will increment CVP.
90
The heart and vessels work together as a unit to
maintain the necessary pressure gradient that will

keep the blood flowing through the main organ

systems. The normal heart at rest pumps 5 l/min of
blood into the arterial system. This represents the
inflow (Qh) . The arterial system regulates the
outflow (Qr) at the level of the arterioles. Normally
this outflow is equivalent to the inflow or 5 l/min. At
this functional level the arterial system sustains a
Mean Arterial Pressure of about 100mm Hg. This
pressure is sufficient to maintain the normal
outflow (Qr). The arterial side is the high pressure
side of the circulation. From the arterial outflow the
blood passes into the capillaries and then the
veins. In the veins the blood encounters a highly
compliant compartment. The CVP is 2mm Hg.
Notice that the veins are 19 times more compliant
than the arteries.
91
If the heart suddenly stops, the Qh is reduced to 0
but Qr remains the same for a little while because
there is still sufficient pressure gradient between
the arteries and veins.
92
Eventually as the Qr drops down to zero blood is
drawn into the more compliant vessels (veins) and
venous pressure is raised from 2 to 7mm Hg. Less
blood remains in the arteries and the pressure
there also drops down to 7mm Hg. Notice that the
drop of pressure in the arteries is in the order of
95mm Hg versus an increment of only 5mm Hg for
the veins. 7mm Hg becomes the mean circulatory
pressure.
93
As the heart is restarted blood is drawn from the
veins into the arteries and arterial pressure is
gradually incremented. Notice the changes in CVP
and Mean Arterial Pressure at this level of cardiac
output.
94
At 1 liter/min of cardiac output enough blood has
been pumped into the arterial side to raise the
pressure and start an outflow which is equal to the
inflow. Notice the little change in CVP versus the
great change in arterial pressure.
Can you explain this? If not go back and restudy
the section on arterial pressure again.
The main factor to understand is that cardiac
function sustains blood pressure by pumping a
certain amount of blood into the arteries. This
pressure at the same time sustains tissue
perfusion. Most of the blood is then capacitatively
stored in the veins (about 70%). When you exercise

the veins constrict and send more blood to the

heart. At the same time heart rate + contractility
increase thus increasing the cardiac output. As a
result mean arterial pressure increase and
perfusion of the muscle and the subcutaneous
circulation also increase. Total peripheral resistance
decreases.

95
NOW THAT EVERYTHING IS FRESH IN YOUR MIND,
GO BACK AND REVIEW THE WHOLE MANUAL!