Greta Donisi

Pecchiari Lesson 11 - 23/03/2015

Mechanical coupling between the heart and the vessels

this man here is Guyton, the

author of the book.

(slide 1, above) What you see here is an electrical circuit consis<ng in a model of several systems in
our body. At the <mes of Guyton, personal computers were not widely available and the easiest
thing to do if you want to simulate something was to build an electrical circuit analog to the system
of your interest. And therefore he made this.Today we are going to study a small part of it.

Page 1


(slide 2, above) Before we go on, we need to summarise all we know about cardiac func<on cur-
ves. We have already said that a cardiac func<on curve describes the rela<on between the preload
and the cardiac work. We dened the preload as the stress exis<ng in the walls of the ventricle at
end diastole and we said that stress is in a unique rela<on with the volume of the ventricle and
therefore we can omit the degree of superimposi<on between thin and thick laments and the
degree of calcium sensi<vity. Weve also said that the stress at level of the ventricles is beyond our
reach; and therefore we use surrogate es<mator of preload. One es<mator of preload is the right
atrial pressure or the central venous pressure, if you want; another surrogate indicator is the vo-
lume of the ventricles at the end of diastole. On the y axis there is a quan<ty in some rela<on with
the cardiac wall, some<me we nd the Work itself, es<mated by the area of PV loop correspon-
ding to a given cardiac cycle, in other cases we nd the stroke volume or, as we see here, the car-
diac output that is stroke volume <mes the heart rate.
And we can start from here (zero) and consider the red curve corresponding to an intrathoracic
pressure of -4 mmHg, the normal intrathoracic pressure at each expira<on, in a young individual.
As you can see increasing right atrial pressure you have an increase of the cardiac output un<l we
reach a plateau. The reason for this par<cular shape of the cardiac func<on curve lays in what we
have seen about the pressure/volume presenta<on of the cardiac cycle. As you increase the pre-
load, the increase of stroke volume is less and less for several reasons:

(slide 3) The rst reason is the following: the
slope of the passive PV curve increases with
increasing volume, so that if you imagine to
increase the central venous P, the correspon-
ding end diastolic volume of the ventricle will
increase less and less with increasing central
venous pressure.

volume is less and less.

What Im trying to say is simply this: here (on

the x) we have the right atrial P, the central
venous P, on the y we have the volume of the
ventricle; with this central venous P we have
this end diastolic volume. Then we increase
central venous pressure and the end diastolic
volume will increase, but ,as the slope of this
rela<on increases progressively with increasing
volume, for a given varia<on of the the central
venous pressure while the increase of the end
diastolic volume is bigger if you start from a
small central venous P, as central venous P ri-
ses we have that the increase of end diastolic

The second reason, for the progressive decrease or increase of the stroke volume, is that at low
end diastolic volume, the corresponding part of the isovolumic maxima curve is almost straight (a
straight line), but if you increase the end diastolic volume the slope of the isovolumic maxima cur-
ve progressively declines and therefore the slope of the aTer loaded maxima curve corresponding
Page 2

to a given situa<on will be less and less as you increase the end diastolic volume. This is the second
reason why the increase of stroke volume with increasing preload is less and less as we move to
higher and higher end diastolic volumes. So we have an almost straight part of the cardiac func<on
curve and then the increase of cardiac output increases as central venous pressure increases un<l
we arrive to a plateau.
(slide 2) In the past there was some debate about what hap-
pens to cardiac func<on curve aTer the rst at part. Some-
body was saying that for very high preload values you have a
decline in the cardiac output; in modern <mes, it is said that
this last part of the curve is never reached in vivo, what we
can say is that even if this part of the cardiac func<on curve
is ever reached its a terminal event in the life of the subject
because you increase the central venous pressure and the
cardiac output decreases, so is something that could happen
near death.
Actually here we dont see only one cardiac func<on curve, we see many of them. Each curve cor-
responds to a dierent value of pleural surface pressure or intrathoracic pressure. So if this is our
control situa<on (the curve examined un<l now) and intrathoracic pressure decreases we have a
net leTwards shiT of the cardiac func<on curve, while when the intrathoracic pressure increases
we have a rightwards shiT of the curve. As you can see all red lines have the same shape, theyre
only shiTed. We understand the reason of this behaviour if we remember that this is just a surro-
gate es<mator. Remembering the Laplace law, stress is propor<onal to the pressure dierence
between the inside and outside of the hollow structure, therefore it is propor<onal to the tran-
smural pressure. Here the value of central venous pressure on the x is always referenced to the
ambient, so it is the pressure inside.
If the pressure outside does not change (4mmHg) there are no problems we have the same curve,
but if the pressure outside changes we will have a change in the transmural pressure and well
have a change in the stress, so we have a change in the volume of the ventricle and therefore a
change in the superimposi<on of thick and thin laments and calcium sensi<vity. When you de-
crease the pressure outside you increase the transmural pressure and so for lower levels of right
atrial P you will have a higher level of cardiac output. When you increase the pressure in the intra-
thoracic space you have the opposite situa<on and therefore for a given level of right atrial pressu-
re, central venous pressure, the cardiac output is less than in control condi<ons. from the clinical
point of view this (5.5 mmHg curve) is not so interes<ng because it happens rarely but this one and
this one (-2 mmHg, +2mmHg curves) are not just an academic discussion because youll see in the
years to come that when you mechanically ven<late a pa<ent you apply also something which is
called Posi<ve End Expiratory Pressure and this pressure applied to the airways of the pa<ent has
the eect of increasing intrathoracic pressure with a consequent tendency for the decrease of the
cardiac output. In the clinical se^ng for reasons that you will understand at the end of the lesson if
you need to employ high levels of PEEP what you do is to expand the intravascular volume increa-
sing mean systemic lling pressure.
Here you also see the broken blue line corresponding to cardiac tamponade, you can imagine that
in the pericardium there is liquid, for example blood, and the eect of this liquid is a change in
shape of the cardiac func<on curve corresponding to a given situa<on.
You are able to see if you consider our control func<on curve that for very low preload values, the
curve corresponding to control condi<ons and the curve corresponding to cardiac tamponade al-
most superimpose, but for higher levels of lling in the case of cardiac tamponade you have a lo-
Page 3

wer cardiac output rela<ve to the control condi<on. (A cardiac tamponade is not a physiological
condi<on).
How can you understand what is going on here? well its preay easy if you remember that a nor-
mal heart is inside the pericardium and the pericardial space in physiological condi<ons is a virtual
space, in the sense that there are few drops of pericardial liquid and the two volume are prac<cally
the same. If I consider a heart i can say that the volume of the heart is equal to the volume of the
pericardium itself. But the total transmural pressure between the outside of the pericardium and
the inside of the ventricle is given by the sum of pressure drop between outside and the pericar-
dial space and between the pericardial space and inside of the ventricle.
So from a mechanical point of view the ventricle and the
pericardium are in series or are in parallel? would you
represent this situa<on with two springs in this arrange-
ment or with this? (he drew two springs in series, rst
drawing, and then two springs in parallel, second dra-
wing). In the second drawing the total force (Ftot) is
equal to F1+F2 (where F1 is the force exerted by the rst
spring and F2 the force exerted by the second spring). In
the rst drawing Ftot=F1=F2. And calling (Delta L) the
change in length of the springs: in the rst drawing (Del-
taL tot)=DeltaL1+DeltaL2, while in the second drawing
(DeltaLtot)=DeltaL1=DeltaL2. We said that the volume
changes of the ventricle are equal to the volume changes
of the pericardium and the total Pressure across the
whole structure is equal to the sum of the pressure
drops across the two structures; so we say that the heart
and the pericardium are mechanically in parallel because
if we want to make parallel with the drawing the Pressu-
re changes are the analog of the force changes and the
volume changes are the analog of the change in length.
Does the pericardium resist to a volume change with
a great pressure? It depends, if we have small volu-
me changes the pericardium wont contribute much
to the total pressure dierence between the inside
and the outside of the structure but for rapid, acute,
big volume changes the pericardium will resist to the
volume change.
It is something like this (he drew a P/V graph) in pas-
sive condi<on the pressure volume rela<on is some-
thing like this, actually this total pressure dierence
between the inside and the outside is given by the
sum of two contribu<ons, one from the ventricular
<ssue itself and the second from the pericardium so
at each volume, for example this, the pressure die-
rence that we measure is the sum of this contribu-
<on a and this contribu<on (the contribu<ons are
the ver<cal distances between the pv curve and x
axis in the 2 graphs, for ventricular <ssue and for pe-
ricardium, that then are summed and give us the
Page 4

distance between the total PV curve and the x axis in the rst graph drawn). the two structures are
mechanically in parallel and therefore the pressure dierence between the inside and the outside
is given by the sum of the pressure dierence across each individual part.
This occurs in normal condi<on: the pericardium develops a signicant pressure dierence only at
very high volumes. This is due to only rapid changes in volume because if a pa<ent of yours has
hypertension and he has a progressive ventricular hypertrophy you have a progressive enlarge-
ment of the heart but also the pericardium enlarges so that wont exert, during the normal wor-
king of the heart, big eects in term of pressure.
Now lets go back to our cardiac tamponade, lets say that something is broken and there is blood
in the pericardium. If this is the situa<on I cannot say that the volume of the heart is equal to the
volume of the pericardium, because it is equal to the volume of the heart plus the volume of the
blood which entered the pericardium.
(going back to P/V graphs he drew) And so lets say that the volume of the ventricle is this one
here, but in this volume we have to add this volume of blood so that the volume of pericardium is
here (the volume on x axis of pericardium is greater than the one of ventricle); in the total PV cur-
ve you have to choose one value of volume as reference, i choose the volume of ventricle, and
then for that volume this is the contribu<on of the ventricle (the ver<cal dierence between PV
curve of ventricle and the x axis) but when this is the volume of the ventricle the volume of the
pericardium is this one, so for this ventricular volume I have to add this pressure dierence so that
the total pressure dierence across the ventricle is this one, the sum of the two. So if we imagine
to do this work imagining a constant amount of blood inside the pericardium you would have so-
mething like this (the passive PV curve is shiTed upwards) and this is the reason why when you
move from a pressure volume representa<on to a cardiac func<on curve you have that the cardiac
output progressively decreases with increasing of the preload.
If we have a tamponade we are in a situa<on in which the ventricle is s< as it would be at higher
volume of lling, so, for a given intraventricular pressure, the ventricle is small because a big part
of the total transmural pressure, at the level of the wall, is absorbed by the pericardium itself. So
the actual preload, the stress in the bers of the ventricle, is small even if the right atrial pressure
is high and because the superimposi<on of thin and thick laments is limited, sorry because the
heart is working at low volume you have that corresponding to a given right atrial P the cardiac
output is small.
We see very small dierences in cardiac output for small level of preload and very big dierences
for intermediate levels of preload.

Page 5


(slide 4) Here we see the eects of
changing the heart rate on cardiac
func<on curves without changing
the stroke volume. and clearly if the
stroke volume does not change for
each of these curves. what Im say-
ing: obviously from here to here you
have change in stroke volume but
the dierence from this cardiac
output and this cardiac output is
not due to the change in stroke vo-
lume but because of change in fre-
quency. As the cardiac output is
heart rate <mes stroke volume, if
we have increase in the heart rate
we have increase also in the cardiac
output; and therefore you have
leTwards rota<on and upwards shiT
of the cardiac func<on curve in the
very same way if at this level of pre-
load you a have a certain level of SV
and if you decrease the heart rate
you should have a downwards shiT
of the cardiac func<on curve (CFC).
In this picture you have also another curve due to a situa<on in which the heart rate is supra op<-
mal and in this par<cular example the op<mal heart rate was 125 beats/min and here the heart is
bea<ng at 175 beats/min as you can see the CFC is bigger than normal but less than the one you
see at op<mal heart rate. Which is the reason for this? It is the lling phase, at a certain point is
useless to increase the heart rate because you have not enough <me for lling.
(slide 5) Here you see the eects on CFC
due to changes in orthosympathe<c
and parasympathe<c s<mula<on and
as you can see during maximal sympa-
the<c s<mula<on you have an upward
shiT of the CFC because for each level
of preload you have an increased in the
SV and you have an increase in fre-
quency in the heart rate. This is 0 sym-
pathe<c s<mula<on, downwards shiT.
And if you have a decrease of parasym-
pathe<c s<mula<on you have a further
shiT downwards of the CFC; this addi-
<onal shiT is due to a decrease of fre-
quency orof SV? frequency because
weve studied that the eect of para-
symp. on contrac<lity of the ventricle
are very very very small.
Page 6


(slide 6) Now please ignore these lines that are va-
scular func<on curves (the descending curves) and
take a look only to the CFCs. You see the eects of
hypoxia this is the control situa<on (thick red line)
and the thin red line is the situa<on corresponding
to moderate hypoxia. If you remember we have said
that the eects of changes in blood gases on heart
rate can be very dierent, in the sense that a mo-
derate degree of hypoxia leads to a decrease of pa-
rasympathe<c s<mula<on to the heart and therefo-
re to an increase in heart rate and therefore for a
given preload and SV you will have a bigger cardiac
output> we have a shiT upwards of the curve
(thin red line). But if hypoxia is severe, we can have
that the parasympathe<c tone increases and mo-
reover we can have a direct eect of hypoxia on
myocardial <ssue, and therefore a decreases in con-
trac<lity and a marked downward shiT of the CFC.
this was all regarding CFCs.
Q: the reason why we have parasymp. s<mula<on on the heart in severe hypoxia is to reduce the
O2 consump<on? A: I dont know.
Now we have to change our point of view and to study vascular func<on curves and we will pro-
ceed in 2 steps. First we have to use our intui<on without any graph and then graphs will arrive.

Page 7


(slide 7, above) Consider a normal cardiovascular system (panel A); this is however a model, the
elements of these model are made by: the pump including not only the two parts of the heart but
also the lungs, so you can imagine this is a pump- oxygenator and its equivalent to the heart-lung
prepara<on of the Frank-Starling mechanism. Our systemic circula<on is made by two compart-
ments, which are arteries and veins, separated by a peripheral resistance. Note that this part of
the model is the same of the model of the arterial compartment weve already studied. So arteries
and veins have a xed value of compliance, peripheral resistance has a xed value of resistance. In
the star<ng condi<on the cardiac output is 5L/min, the arterial pressure is 102 and the venous
pressure is 2mmHg so that the pressure dierence across the peripheral resistance is 102-2=
100mmHg, divided by the ow it gives a value of 20mmHg/L/min as the value of resistance.
(panel B) We can imagine that we have a cardiac arrest, so that the pump suddenly stops.
for the owners of Guyton book it always call improperly cardiac output the ow between the leT
ventricle and aorta and venous return the ow from venous compartment to the right ventricle.
the two things at least at the equilibrium are the same and this is not the terminology used by
Guyton.
here we have the cardiac output instantly goes to 0; what happens to venous return? At the same
instant of the arrest we have that the pressure in the arterial compartment is again 102 and the
pressure in venous compartment is s<ll 2. So there is a pressure dierence between the arterial
and venous compartment that enables a ow through resistances of 5 as before, but now we dont
have the pump moving blood from venous to arterial compartment, and so the pressure in the ar-
terial compartment decreases and the P in the venous compartment increases, while the Volume
Page 8

in the arterial compartment decreases and the V in the venous compartment increases, this goes
on un<l there is no more pressure dierence between arterial and venous compartments, when
the pressure is exactly the same everywhere and therefore the volume transfer stops. which is the
pressure in my circuit aTer the cardiac arrest and aTer the stabilisa<on of the system? By deni-
<on, as we said in the rst lesson, the pressure in the circuit is the mean systemic lling pressure.
Note that as the veins are much more compliant than the arteries you have that the same volume
change in both compartment causes a marked decrease of arterial pressure and a small increase of
venous pressure. So from a value of 102 we go to a value of 7 mmHg in the arteries and from a va-
lue of 2 you go to a value of 7 mmHg in the veins.
(Panel D) Now imagine that our pa<ent is lucky or is reanimated and the pump starts again but at
lower rate than before so at the beginning the CO is just 1L/min. In the instant at which the CO
begins the pressure in the venous compartment is equal to mean systemic lling P so that no ow
is present through the peripheral resistances but as the heart transfer blood from the venous to
the arterial compartment the P in arterial compartment rises and the P in the venous compart-
ment decreases un<l there will be a P dierence that for the given value of resistance will results in
a ow of blood through resistances equal to the cardiac output that is in our example 1l/min.

(Slide 9)These events have been represen-

ted in a numerical situa<on in this graph
in which you see the dependence of arte-
rial P and venous P on the CO. (CO,0; CO,1;
CO,5) when CO is 0 all pressures are equal
(7mmHg) when CO is 1 arterial P is 26 and
venous P is 6 and when CO is 5 arterial P is
102 and venous P is 2.

Page 9

(Slide 8)But this things have been

veried also in animal experiments
and the heart was replaced by an
ar<cial pump that could generate
dierent CO, and on the x you have
<me. As you decrease tho CO you
have a decrease of arterial P and
an increase of central venous P.

(Slide 10)Now considering the 3 si-

tua<ons that we have studied (CO,0;
CO,1; CO,5) if you build a graph on
which you put on the x the CO, whi-
ch is our independent variable, and
on the y the central venous P you
will have something like this, when
CO is 0 the pressure is equal to
mean systemic lling pressure, and
in a normal man is about 7; when
you increase the CO to 1 the central
venous P becomes 6 and if you fur-
ther increase the CO to 5 you have
the central venous P that reach
normal P 2. And if you join these 3
points you will have a straight line
called vascular func<on curve. Note
that the line is straight only un<l
central venous P is greater than 0
aTer you have a ver<cal line, you
change the central venous P but the
CO won't change.
And this is due to the fact that when
the veins enter the thorax you can
have the forma<on of a Starling's re-
sistor, the P in the thorax is sub atmospheric and therefore you can have a posi<ve transmural P at
level of the ventricle even when nega<ve values of central venous P and therefore you are in a si-
tua<on in which the P surrounding the last part of the veins in the abdomen can be slightly posi<-
ve and greater than the P near the heart and therefore you have a Starling's resistor and you enter
a situa<on that is called Fluid limita<on, we change the driving pressure but nothing happens to
the cardiac output.

Page 10

(slide 11, above) the next step is to understand which are the determinants of this cardiac curve. In
order to do so we have to assume a model, you see the model I've chosen which is one of the se-
veral models presented by guyton himself. This is an electrical representa<on of the model, but we
can take a look at the hydraulic representa<on (drawing).

Our model is made by a compliant arterial compartment, a compliant venous system, a peripheral
or arteriolar resistance between them ( Ra) and other resistances between the venous compart-
ment and the right atrium (Rv). The choice of the modal is arbitrary and on Berne and Levy they
use a dierent model, without Rv and the atrium, which is instead included in Guytons model. The
problem is that it's just a model, to relate the elements of the model to the real cardiovascular sy-
stem. If you put resistances here and you say this is venous resistance, this can be only the resi-
stance oered by the big veins of our body, but not all the resistance of the venous compartment
is due to big veins, most of it is due to venues, small veins and so on; this is a simplica<on. I choo-
Page 11

se to use this model simply because it will highlight the dependence of the CO on the resistance of
the terminal part of the venous compartment. This is maybe not of interest for physiologists be-
cause most of the control of peripheral resistances is made at level of arteriolar resistance. But in
several clinical situa<ons we have narrowing and compression of the big veins and this can cause
Rv to increase and therefore the cardiac output falls. So Pa is arterial pressure, Pv venous pressu-
re, Pf is the lling pressure, we can think it is central venous pressure or end diastolic pressure in-
side the right ventricle. Ra and Rv are the resistances at the end of arterial and venous compart-
ment and Ca and Cv are the compliance of arterial and venous compartment.
(slide 12) We dont need to
remember all passages but
only some deni<ve points
that you already know. At
the end of this algebra you
will nd the equa<on de-
ning the mean systemic l-
ling pressure, already seen in
the rst lesson. That is vo-
lume of the blood minus the
unstressed volume of all the
circuit divided by the com-
pliance of the whole circuit.
(slide 13) At the end of some other al-
gebra we nd an expression for the
cardiac output; again this is not a big
discovery! It tell you: the dierence
between the inlet of the circuit (Pa) and
the outlet of the circuit (the lling pres-
sure in the right atrium) divided by to-
tal Res is equal to the cardiac output. If
you look at the circuit made in this way
you see that the two Res that we have
are in series and the total resistance of
the system is the sum of the 2 and the
total pressure drop across the circuit
divided by the resistance is equal to the
ow that is the cardiac output.
however, we cant stop here because in this situa<on we have two parameters (resistances) of the
model which are xed, at least in our assump<ons, but the pressures and ow depend one on
each other, because if you increase the cardiac output you will increase arterial pressure if resi-
stances are constant. We want a rela<on that relates the CO to the lling pressure, all the other
symbols here should be xed parameters of the model.

Page 12

(slide 15) More algebra and we obtain the equa<on of the vascular func<on curve it says that the
lling pressure (central venous pressure) is equal to mean systemic pressure plus the ow mul<-
plied by minus this expression here, that is nothing but a resistance (but note that the resistance
mul<plied by the CO is not the res of a par<cular part of my cardiovascular system, it is a composi-
te resistance. Given by the sum of the venous resistance and the ra<o of the compliance of the ar-
terial compartment divided by the total compliance mul<plied by the arterial res. The arterial
compliance is very small compared to venous compliance and therefore you can imagine that Ca/
(Ca+Cv) will be a very small number, that then is mul<plied by a very big number, because the arte-
rial resistance is much bigger than venous resistance This composite resistance is what Guyton
calls resistance to venous return (given by venous resistance plus a term considering arterial res).
If we want to obtain an expression in the form CO equal to a func<on of lling pressure we can do
this and this is the result (last equa<on of the slide). The CO is equal to the dierence between the
mean systemic lling pressure and the lling pressure divided by the venous res plus arterial res
mul<plied by the ra<o between the compliance of the arterial compartment and the total com-
piance.

Page 13

(Slide 16) Now compare the rela<on we've found with our line. The intersec<on between the y
axis and the vascular func<on curve is mean systemic pressure, actually we already knew this,
anyway we nd here, the intersect is Pms; the slope depends both on compliances and resistances
because it is given by minus this expression. Now We can see how the vascular func<on curve
changes in a number of situa<ons.
(slide 17) Here we have changes of the
curve with change in intravascular volu-
me. This is the control curve in normal
situa<on, if you have a transfusion you
will have an upward shiT of the vascular
func<on cur with any change in slope.
The reason is clear if you look at the
equa<on, if you add volume inside the
vascular compartment what you are
doing is increasing mean systemic lling
pressure, in the assump<on that the
other parameters of the volume are in-
dependent on the state of lling, and the-
refore the only dierence between the
two curves is simply the increase of the
intersect without any change in the slope.
This is the explana<on based on the
equa<on but if you want you can go with
intui<on. Let's consider the simpler mo-
del, we have only the arterial compart-
ment, the venous compartment and the
peripheral res. All these 3 parameters are
independent on the state of lling of the
circula<on, in order to have ow we
Page 14

should have a P dierence between the arterial and venous compartment and therefore you have
to transfer blood from the venous to the arterial compartment, if the values of venous and arterial
compliance are unaected by the degree of lling, for a certain volume change you will have a cer-
tain pressure dierence that will correspond to a give ow through the peripheral res, and this P
dierence will be independent on the state of lling and therefore increasing the cardiac output
we'll have a certain decrease of the central venous pressure which will be independent on the star-
<ng value of central venous pressure.
This is the eect of a change in intravascular volume but, without changing slide, we can also see
the eect of the change of the tone in smooth muscle at the level of the veins. Let's say that we
have venous constric<on, which is the main eect? You may think The increase of venous res, but
we've said that the venous res here is actually the res of very big veins; so if you have vasoconstric-
<on the main eect is the decrease of unstressed volume and if you decrease the unstressed vo-
lume the mean systemic lling pressure increases. So instead of wri<ng transfusion I could have
wriaen venous construc<on and instead oh hemorrhage I could have wriaen venous vasodila<on.

(Slide 18) We can also see which are the eects

on vascular func<on curve of the changes in the
res, arteriolar constric<on or constric<on of big
veins. When we change the tone of the resistan-
ce vessels the corresponding vascular func<on
curve has the same origin but dierent slopes.
The reason for this is that is assumed that most
of res is oered by arterioles, metarterioles and
capillary sphincters but the volume contribu<on
of these vessels to the total volume in circula<on
is rather small so when you cause vasoconstric-
<on at this level you don't have a change in the
unstressed volume (we're not talking about ve-
nules or veins that contain a huge amount of
blood). So because of this when we have arterio-
les vasoconstric<on we have a change in res wi-
thout a change in the unstressed volume. If it's
the case then the mean systemic lling P should not be changed by the arteriolar vasoconstric<on.
During arteriolar constric<on during sympathe<c s<mula<on the situa<on is dierent, since also
the unstressed volume is changed. But here I'm talking about only arteriolar vasoconstric<on so
you have that this coecient become grater and therefore the slope is increased. We have to say
that for the same cardiac output, the central venous pressure will be lower with an increase of the
resistances. In the same way, we can imagine that if there is a mass compressing the big veins this
will cause an increase in the venous resistance, which will cause a similar increase in slope in the
vascular func<on curve. Even if the absolute change of venous resistance can be less than a given
change of arteriolar resistance, this change can have a rela<vely bigger eect on cardiac output
because Ra is mul<plied by a very small number, while Rv is not mul<plied by anything. In the very
same way if you decrease the res you will wave vasodila<on and therefore a counterclockwise ro-
ta<on of the vascular func<on curve.

Page 15

(Slide 19, above) It is important to realize that we have a poten<al problem, because we studied
than increasing the preload we increase the cardiac output, but now we see that when you increa-
se the cardiac output the preload decreases. It is apparently a dierent concept from what we're
telling before. Actually If we remember the setup used for Frank-Starling mechanism, the circuit
was not a complete circuit between aorta and veins, you had the isolated heart, the Starling's resi-
stor and then there was a vessel to collect the blood that then was sent to the right ventricle.
Also this rela<on shows something that is completely true for an isolated prepara<on but if we
have to put together the pump, described by Frank-Starling mechanism and the vessels which are
described by the vascular func<on curve we have to superimpose the vascular func<on curve with
the cardiac func<on curve. In order to do so you need to switch the axes for the vascular or cardiac
func<onal curves, because the VFC has the central venous pressure on the y while the CFC has the
central venous pressure on the x. Tradi<onally you switch the VFC and so it becomes this one.
From a geometrical point of view the condi<ons in which the value of Coz and of central venous P
sa<sfy both the CFC and VFC a is the intersec<on between the two curves, the D point. This graph
is telling you simply that if you have a certain pump described by CFC a and a certain circula<on
described by VFC the only possible value of CO and central venous pressure is indicated by the in-
tersec<on between the two curves.

Page 16

To try to understand what this graph means from a physical point of view we can imagine to do an
ideal experiment and it's described in Berne and Levy for who is reading it. We can imagine to do
the following, very quickly, instantaneously we take an amount of blood from the arterial com-
partment and we transfer to the venous compartment so that the total intravascular volume is not
changed, when you take a volume of blood from the arterial to the venous compartment you have
that the volume of the venous compartment is increased and therefore the pressure of the venous
compartment should be increased too, this is shown here from point D to point A; we can imagine
that the transfer is instantaneous so we have not change of the CO with the change in central ve-
nous pressure. But we know according to the CFC for this level of preload this level of CO should
correspond so that if you do this opera<on you will see that immediately aTer the adding of blood
CO suddenly increases at the value indicated by B. Now you are in B and then the heart beats again
and another volume of blood is transferred from the venous to the arterial compartment; the ef-
fect of this transfer will be a decrease of P in the venous compartment because for the values of
arterial P and central venous P that we have the P dierence across the peripheral resistances is
too low to give a CO like the one you have here, so at the rst beat you are adding (?), with each
subsequent beat you are increasing the volume in arterial compartment rela<ve to the venous
compartment. This goes on un<l the volume in arterial and venous compartment are su he that
there is a P dierence between the arterial and venous compartment so that for a certain value of
resistance you will have a venous return equal to the CO and this happens when you arrive here
which is the intersec<on of the VFC and the CFC. So this is the equilibrium point you can imagine
you can destabilize the system taking the point corresponding to your situa<on away from equili-
brium but spontaneously the system will end here.

(Slide 20) This way to represent the car-

diovascular system is very useful to repre-
sent the changes the cardiovascular sy-
stem can undergo. Here you see the eect
of the sympathe<c s<mula<on at level of
myocardium, as you can see you have no
change in this representa<on of the VFC,
it means that the unstressed V is unchan-
ged, the Res are unchanged; You just s<-
mulate the myocardium.
As you have seen before the CFC will shiT
upwards because of increase of contrac<-
lity and because of increase of heart rate.
However the change in CO that we have
due to sympathe<c s<mula<on is not gi-
ven by the ver<cal distance for this value
of central venous P between point A and B, this would be the ini<al case imagining wrongly that
the increase of orthosympathe<c tone is sudden because this is not the intersec<on of the CFC and
VFC in the new situa<on, the point of intersec<on is D here. In point D you have a CO that is grea-
ter than control condi<on but you have also a decrease in central venous P.
This slide is giving you a general message: when you have an increase of CO because of increase of
contrac<lity of the myocardium you have that the CO increases and the central venous pressure
decreases, as you see here.

Page 17

(slide 21) We can also see the eect of a

transfusion. This is the CFC(green line) this is
the VFC in control situa<on(red) and this is
VFC aTer transfusion (blue). Transfusion cau-
ses the CO to increase but a the very same
<me you have also an increase of central ve-
nous P. You can imagine now very easily
what occurs during hemorrhage; the vascu-
lar func<on curve moves downwards and to
the leT, so if this was the equilibrium point
in normal condi<ons aTer the hemorrhage it
will be here, and here aTer the hemorrhage
both cardiac output and central venous
pressure are reduced.

(slide 22) This is more dicult. You have the representa<on of what happens when you change re-
sistance of the systemic circula<on; at the level of the vascular func<on curve you have a down-
ward shiT and rota<on, while for the cardiac func<on curve we have a variable situa<on: by itself,
a decrease in preload would cause a tendency for the stroke volume to be reduced, but a normal
leT ventricle (in heart-lungs prepara<on or in vivo) is rather insensi<ve to the changes of aTerload
and therefore this CFC would be rather
xed for a normal subject in the presen-
ce of an increase of resistances; on the
other hand, if we think of a subject with
heart failure, he can be in a situa<on in
which his cardiac output is markedly af-
terload dependent and therefore the CFC
a will shiT downwards. In all the possible
situa<ons if we increase the aTer load
you have a decrease of the CO, small or
big. What happens to the central venous
P depends on the amount of change of
the CFC a and of VFC; if you imagine that
the CFC is almost in the same situa<on
as in the normal subject you will have a
decrease of the central venous P, but if
you imagine,as in the heart failure pa-
<ent, to have a shiT of the CFC you can
have a decrease of CO with an increase
of central venous P.

Page 18

Q: in the model in which we have also the resistances, why Rv is only due to big veins?
A: because you can if you want think about the resistance of the small veins but the fact is that Rv
occurs aTer the compliance soma least in the model should be aTer the capacitance vessel. Guy-
ton made several of these models with dierent subdivisions of the venous compartment of the
arterial compartment and so on and each of this compartment was represented by a compliance
and a resistance. I choose this one because it is rather simple and gives you an idea of what hap-
pens when you change arteriolar resistances and when you compress the veins.
You can imagine that if the venules and small veins were the big capacitance vessels you could
stretch the model and say that Rv is the resistance aTer these vessels.

Page 19