Objectives have been taken from The American Physiological Society Medical Curriculum Objectives Project

http//:www.the-aps.org/education/MedPhysObj/medcor.htm
In some case, the order of the topics and the objectives have been modify

01. Understand the principles underlying cardiac output measurements made using a) The
Fick’s method and b) indicator dilution methods using a Swan-Ganz catheter
Calculate CO by using Fick’s method

02. Understand the concept of “mean systemic pressure”, its normal value, and how various
factors can alter its value.
Construct a vascular function curve. Identify on the curve the normal central venous
pressure and mean circulatory pressure. Predict how the curve is altered by a) changes
in resistance to venous return and b) changes in blood volume or vascular compartment
size.
Define venous return. Understand the concept of “resistance to venous return” and know
that factors determine its value theoretically, what factors are most important in practice,
and how various interventions would change the resistance to venous return.

03. Know how cardiac function (output) curves are generated and how actors which cause
hyper effective or hypo effective changes (contractility) in the heart can alter the shape of
cardiac function curve.

04. Use a combined cardiac output / venous return graph to predict how interventions such as
hemorrhage, increase in preload, acute and chronic heart failure, autonomic stimulation or
ihibition, and exercise will affect cardiac output and right atrial pressure. Predict how
physiological compensatory changes would alter acute changes.

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I. Cardiac output (CO)

Is the volume of blood pumped into the aorta each minute by the left ventricle.
For a 70kg man normal values are HR=70/min and SV=70ml, giving a cardiac output of about
5litre/min. . CO can be increased to 20 l/min depending on the body’s demand for O2.

A. The cardiac index is the cardiac output per square meter of body surface area, normal
2
values range from 2.5-4.0 litre/min/m .

Body surface area normalizes for different shapes, heights and weights. Tables are available
that estimate body surface area from weight and height. An average surface area is 1.73 square
2
meters (m ). Therefore a person with an average cardiac output of 5 l/min would have a Cardiac
2 2
Index of: 5 l/min ÷ 1.73 m = 2.89 l/min/m .

II. Methods of measuring the Cardiac Output

1. Fick’s principle
2. Dye dilution
3. Thermodilution
4. Doppler techniques

1. The Fick’s Method

Flow can be measured by adding (or removing) a substance to the liquid as it passes through
the tube.
Blood is pumped from the venous system through the lungs to the arterial system. In the lungs,
O2 is taken up into the blood stream. The total uptake of O2 by the lung per minute has to be
equal to the product of the pulmonary blood flow per min. and the difference in O2 concentration
in pulmonary venous and pulmonary arterial blood.

The O2 uptake can be measured by spirometry. Arterial and venous O2 concentrations can be
measured by withdrawing and analyzing blood from both vessels.
Therefore:
Cardiac Output = O2 consumption/min ÷ (aO2 - vO2)

2. Indicator-dilution method

A known quantity of a dye is injected into the right atrium via catheter. A measured quantity of
an indicator (dye) is injected into a large central vein or into the right side of the heart through a
catheter. Arterial blood is continuously drown and passes through a photosensitive device that
measures the dye concentration. The resulting curve measures dye concentration as a function
of time.

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The area under the dye-dilution curve can be calculated and approximates the average
concentration of dye over time. Knowing the quantity of dye injected, the cardiac output can be
determined by:
Cardiac output = Quantity of dye injected ÷ area under the curve

3. Thermo-dilution technique

The procedure is the same, but blood temperature is measured instead of dye color. A cold
dextrose solution (2.5-10 ml) is injected through one part (proximal opening) of a double
lumen catheter which is positioned near right atrium and a small thermistor attached to catheter
tip lies in pulmonary artery and measures the profile of temperature change with time.
The degree of change in the temperature is inversely proportional to the cardiac output. Then:

Increased blood flow (and CO) = Minimal temperature change

Decreased blood flow (and CO) = Pronounced temperature change

Plotting this temperature change against the time it took for the cooler fluid to reach the
thermistor gives us a thermo dilution curve, a computer built into the monitor calculates and
integrates the area under the thermo dilution curve, and gives a digital readout of the cardiac
output in L/min

4. Doppler techniques

Is a non-invasive technique. The machines transmit an ultrasonic vibration into the body and
record the change in the frequency of the signal that is reflected off the red blood cells, so
Doppler techniques measure velocity, not flow. The flow could be obtained by integrating the
signal over the cross-sectional area of the vessel.

The velocity of blood in the ascending aorta may be measured using the Doppler effect. The
length of a column of blood passing through the aorta in unit time is estimated and then
multiplied by the cross-sectional area of the aorta to give stroke volume.

III. Central venous pressure (CVP) monitoring

The central venous pressure (CVP) measures the filling pressure of the right ventricular (RV); it
gives an estimate of the intravascular volume status and is an interplay of the (1) circulating
blood volume (2) venous tone and (3) right ventricular function.

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A. Waveforms in CVP

The normal CVP waveform consists of three upwards deflections (a, c, & v waves) and two
downward defections (x and y descents). These waves are produced as follows:

1. The ‘a’ wave is produced by right atrial contraction and occurs just after the P wave on the
ECG.
2. The ‘c’ wave occurs due to isovolumic ventricular contraction forcing the tricuspid valve to
bulge upward into the right atrium. (RA)
3. The pressure within the RA then decreases as the tricuspid valve is pulled away from the
atrium during right ventricular ejection, forming the X descent.
4. The RA continues to fill during late ventricular systole, forming the V wave.
5. The Y descent occurs when the tricuspid valve opens and blood from the RA empties rapidly
into the RV during early diastole.(1

B. Pulmonary artery and pulmonary capillary wedge pressure monitoring

The pulmonary artery catheter (PAC) help to monitoring the pulmonary artery (PA) pressure,
pulmonary capillary wedge pressure (PCWP) as well as central venous pressure (CVP).
The PCWP under most circumstances provides an accurate estimate of the diastolic filling
(preload) of the left heart.

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C. Factors that influence RAP:

Atrial contraction
Intrapleural pressure
Posture
Blood volume
Intrinsic venous tone
Sympathetic neural tone to veins
Venous pump (exercise

IV. Venous return must equal cardiac output.

Over time cardiac output and venous return must be equal for each ventricle, although transient
differences can occur. Changes in posture, such as lying down, can briefly increase venous
return. The resulting change in the preload should increase cardiac output. But the vascular
system is a closed circuit, blood pumped from the heart returns to the heart, therefore, venous
return must equal cardiac output over time.

V. Determinants of Cardiac Output

CO is the product of heart rate (HR) and stroke volume (SV):

CO = HR x SV

A. Heart rate: is determined by the rate of spontaneous depolarization at the sinoatrial node
and is modified by the autonomic nervous system. The vagus nerve acts on muscarinic
receptors to slow the heart, whereas the cardiac sympathetic fibers stimulate beta-adrenergic
receptors and increase heart rate.

B. Stroke volume is determined by three main

factors: preload, afterload and contractility.

1. Preload: is the ventricular volume at the end

of diastole.
An increased preload leads to an increased stroke
volume.
Preload is mainly dependent on the return of
venous blood from the body.
Venous return is influenced by changes in
position, intra-thoracic pressure, blood volume and
the balance of constriction and dilatation (tone) in
the venous system.

As the EDV (end-diastolic volume) increases and stretches the muscle fiber, the energy of
contraction and stroke volume increase, until a point of over-stretching when stroke volume may
actually decrease, as in the failing heart. Cardiac output will also increase or decrease in
parallel with stroke volume if there is no change in heart rate.

2. Afterload: is the resistance to ventricular ejection. This is caused by the resistance to flow
in the systemic circulation and is the systemic vascular resistance. The resistance is determined
by the diameter of the arterioles and pre-capillary sphincters; the narrower or more constricted,
the higher the resistance. The level of systemic vascular resistance (total peripheral resistance
TPR) is controlled by the sympathetic system which controls the tone of the muscle in the wall
of the arteriole, and hence the diameter.

3. Contractility describes the ability of the myocardium to contract in the absence of any
changes in preload or afterload. In other words, it is the "power" of the cardiac muscle. The

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most important influence on contractility is the sympathetic nervous system. Norepinephrine
stimulate Beta-1 adrenergic receptors, and contractility increases.

VI. Vascular function curves

State the relationship of right atrial pressure (RAP) and venous return (VR). When graphed the
independent variable is the CO, and the dependent variable is the CVP.

A. The major determinant of venous return

1. Is the systemic filling pressure . This is the difference between peripheral venous
pressure and right atrial pressure (Right atrial pressure is typically ~ 2 mmHg with a mean
systemic filling pressure of 7 mmHg. At this pressure difference (7 - 2) and the low resistance of
the venous system, venous return is approximately 5 l/min.

2. Blood transfusion or retention of salt and water results in an increase of Pcm, then would
increase the pressure difference and increase venous return
Hemorrhage would reduce peripheral venous pressure and reduce venous return for a given
right atrial pressure.
The vascular function curves by effect of changing circulatory volume are parallel to each other.

VII. The cardiac function curves. The Frank–Starling Principle :

This principle illustrates the relationship between cardiac output (CO) and left ventricular end
diastolic volume (LVEDV), or the relationship between
stroke volume and right atrial pressure.

The relationship between LVEDV and SV is known as

Starling's law of the heart, which states that the energy
of contraction of the muscle is related/proportional to
the initial length of the muscle fiber (left graph)

A. An increase in LVEDV (preload)

The ventricular fiber length is also increased, resulting
in an increased tension of the muscle.

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An increase in preload (going from point A to B or from
C to D in the graph at the right) will increase the
cardiac output until very high end diastolic volumes are
reached. At this point cardiac output will not increase
with any further increase in preload, and may even
decrease after a certain preload is reached.

B. Change in contractility
Any increase or decrease in the contractility of the
cardiac muscle for a given end diastolic volume will act
to shift the curve up or down, respectively. (see graph
at the left)The curves show how the heart performs at
different states of contractility, ranging from the normal
heart to one in cardiogenic shock. This is a condition
where the heart is so damaged by disease that cardiac
output is unable to maintain tissue perfusion. Also
shown are increasing levels of physical activity which
require a corresponding increase

D. Afterload
Relationship
between stroke volume and afterload. A series of curves
illustrates the effects of increasing afterload on systemic
vascular resistance.

As afterload increases, the patient moves to a lower curve,

with a lower stroke volume for the same ventricular end-
diastolic volume (preload).

VIII. Interaction of Cardiac and Vascular Function Curves:

Simultaneous plots of cardiac output and venous return as a function of end diastolic volume (or
right atrial pressure.

A Cardiac Function Curve:

This is simply the Frank-Starling curve
for the ventricle showing the relationship
of cardiac output as a function of end
diastolic volume.

B. Venous Return Curve. This is

the relationship between blood flow in
the vascular system (venous return) and
right atrial pressure.

C. Mean Systemic Pressure

This is the point where the venous
return curve intersects the X axis. The
mean systemic pressure reflects the right atrial pressure when there is ‘no flow’ in the system.
At this point the pressure is equal throughout the circulatory system.

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D. Equilibrium point:

This is the steady-state where the two curves intersect; it reflects the point where cardiac output
is equal to venous return.

E. Factors that affect CO

Cardiac output can increase or decrease by
altering the Frank-Starling curve, the venous return
curve, or both; some predictions can be made by
examining how the curves shift as the variables
change.

1. Inotropic Changes:

Contractility is determined by various autonomic

mechanisms and certain drugs (such as digitalis).
Inotropic changes will alter the slope of the cardiac
curve up or down (as discussed above).

a. Positive inotropic agents, such as digoxin or

sympathetic stimulation, will increase contractility
and therefore increase the cardiac output. This
new equilibrium point now reflects an increased
CO and a lower RAP (more blood is now being ejected from the heart with each beat).

b. Negative inotropic agents have the opposite effect, decreasing contractility and CO, and
increasing RAP.

2. Total Peripheral Resistance

Changes: TPR is determined by the resistance of the arterioles. Changes in TPR will change
the slope of both the cardiac function curve and the venous return curve.
a. An increase in TPR (left side
graph) will cause blood to be
retained on the arterial side of
circulation and will increase the
aortic pressure against which the
heart must pump.
This will act to shift both slopes
downward. As a result of this
simultaneous change, both the
cardiac output and the venous return
are decreased, however the right
atrial pressure remains the same .

b. A decrease in TPR (not shown)

will allow more blood to flow to the
venous side of circulation and will
lower the aortic pressure against
which the heart must pump. This will shift both slopes upward. Both cardiac output and venous
return will be simultaneously increased; again, right atrial pressure will remain the same

3. Exercise.

Cardiac output will change to match changing metabolic demands of the body. The outputs of
both ventricles must be identical, and also equal the venous return of blood from the body.

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During exercise the cardiac output and venous return are balanced. Blood vessels dilate in
exercising muscle groups because of increased metabolism, and blood flow increases. This
increases venous return and right ventricular preload.
More blood is delivered to the left ventricle and cardiac output increases.
Associated with exercise there is an increase in sympathetic activity that will lead to an
increased contractility and heart rate, further increasing cardiac output to meet tissue
requirements.

IX. Role of Heart Rate (HR) in control of cardiac output (CO)

A. Changes in HR alters:

1. Preload An increase in HR decreases

diastolic time
2. Afterload An increase in HR alter CO, and
changes in CO alter BP
3. Contractility an increase in HR increases net
Calcium influx/min –Rate induced regulation-

B. Graph analysis

The graph to the right shows the effect of

changes in HR on CO when the rate of the
atrium is paced and gradually increases.

1. A change in HR from 50 to100 causes a

decrease in SV but an increase in CO
2. A change in HR from HR 100-200 causes a
decrease in SV but CO remains practically
constant
3. A change in HR from HR 200 to 250 causes
a decrease in SV and a drastic decrease in CO

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X. CONGESTIVE HEART FAILURE

A. Definition:

Impaired contractility of the myocardium

that is not able to provide adequate blood
flow to the meet the needs of the tissues.
Below figures show that in a patient with
heart failure, the chronically low blood
pressure causes the kidney to retain fluid
in an attempt to restore it. Because
contractility is impaired, fluid retention
can not restore the cardiac output.
Venous pressure increases (venous
congestion) with the consequent edema
formation (increased capillary filtration)

B. Acute heart failure (HF)

Sudden coronary occlusion

No change in blood volume
Cardiac function curve shift downward, and the equilibrium point is where it intersects the
normal vascular function curve
Change from equilibrium point A to point B (moderate HF) or from A to C (acute HF)

C. Chronic heart failure

Hypertension, ischemic heart disease

Increase in blood volume because of kidney
retention
Change from the equilibrium point A to point
D (moderate HF) or from A to E (severe HF)

D. Signs and symptoms:

Fatigue
Low exercise tolerance
Venous congestion and edema
Dyspnea
Reduced ejection fraction

E. Compensations

Fluid retention raises venous pressure

Healthy chamber pumps blood into the weak chamber.
Failure is often on only one side of the heart. Thus the healthy chamber can greatly raise the
venous pressure of the affected chamber even without fluid retention. Often seen in acute
infarction of the left ventricle where pulmonary edema occurs.

F. Causes of hypertrophy/failure

1. Pressure overload causes concentric hypertrophy where the ventricle remodels inwardly
causing low lumen volume and thick wall. Caused by hypertension or outflow track
obstruction.
2. Volume overload leads to eccentric hypertrophy. The heart remodels outwardly to give a
large lumen volume and a thin wall. Caused by regurgitant aortic valve or AV fistulas.

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