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Various fields of application

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Special Edition:
Cardiopulmonary Exercise Testing
Information, Diagnostics, Essays
1st edition, April 2002
Editorial

CPET Table of Contents

History, approaches and applications Essay
Exercise Testing: The "How" and the "Why"
Author: Prof. Brian J. Whipp Ph.D., D.Sc. .............................. 3

Fields of Application
CPET - Various Fields of Application
Indications and relevance of CPET .......................................... 8

Diagnostics
Oxycon Pro
CPET of the Highest Quality .................................................. 10

Dear readers,
It has always been the wish of mankind to go to the limits of
Practical Guidelines
our capacities. Even the ancient Greeks used to send messages CPET- Practical Guideline
through couriers who were able to run hundreds of miles in a Author: Wolfgang Mitlehner, M.D. ........................................ 12
couple of days. If the first marathon runner in history had had
our knowledge and had been trained according to current stan-
dards, he would not have collapsed of exhaustion after having
Diagnostics
been informed of the first Athenian victory over the Persian Vmax and Cardiosoft
troops in 490 b.c. However, despite our medical findings, car- CPET made by SensorMedics,
ECG made by Marquette Hellige ........................................... 20
diopulmonary exercise testing is still a fascinating subject for
physicians and researchers of various medical fields. Oxycon Mobile ....................................................................... 23
This first special VIASYS info edition is especially aimed at
clinicians who wish to be informed about reasons, indications Essay
and interpretation of cardiopulmonary exercise testing and who Clinical Relevance of CPET
are interested in their collegues' research findings. Author: Prof. Karl-Heinz R¸hle, M.D. .................................. 24
Apart from its application in athletic performance, cardiopul-
monary exercise testing can be used in various medical fields
(an overview of which is provided on page 8). Until now, exer- Essay
cise testing has only been practiced by experts. Today we see Evaluation and Interpretation
an increasing interest from healthcare providers. We hope to of a cardiopulmonary exercise test
inform you with interesting literature suitable to support you Author: Hermann Eschenbacher, Ph.D. ................................. 26
in your daily work. If you are interested in learning more about
cardiopulmonary exercise testing - please read through our bro-
chure or simply refer to the literature references on page 31.
The Last Page
Literature references, Training courses, seminars .................. 31
Sincerely Yours,

Paul ter Grote

Managing Director of Erich JAEGER GmbH,
a subsidiary of VIASYS Healthcare

2 VIASYS info Special Edition CPET, April 2002

 Essay

Exercise TTesting:
esting: The "How" and the "Why"

Brian J. Whipp, Ph.D., D.Sc.

Centre for Exercise Science and
Medicine, University of Glasgow,
Glasgow, UK

Strategies designed to increase exercise

1. Aims tolerance in such patients should therefore
To address the role of exercise testing in elucidating the causes of exercise intolerance, attempt both to increase (where possible) the
with particular reference to pulmonary disease. ventilatory limits, reduce the demand for
To discuss the value of clinical exercise testing, in: ventilation and reduce the intensity of, or
a) establishing the limits of system function attempt to desensitize the subject to, the
b) defining the effective operating range consequent dyspnoea.
c) identifying potential causes of exercise intolerance In order to meet the increased demands for
d) evaluating the normalcy of the response with regard to a reference population pulmonary gas exchange during exercise, the
e) establishing the normalcy of response with regard to other physiological lungs must replenish the O2 extracted from
functions the alveoli by the increased flow of more
desaturated mixed venous blood. This
f) providing a frame of reference for change with respect to therapeutic
preserves alveolar, and hence arterial, O2
interventions or training, and
partial pressure. The lungs must also provide
g) as a means of "triggering" an abnormality. to the alveoli diluting quantities of CO2-free
To emphasise the importance of domains of exercise intensity and identifying the (atmospheric) air at rates commensurate with
determinants of an "appropriate" ventilatory response, including considerations of: the increased delivery rate of CO2 in the
a) to what extent are the "requirements" met? mixed venous blood. This maintains alveolar,
b) what is the "cost" of meeting these requirements? and hence arterial, PCO 2 . However, the
c) to what extent is the system "constrained" or "limited"? and metabolic (chiefly lactic) acidosis of high-
intensity exercise requires that alveolar and
d) how "intensely" is the response perceived?
arterial PCO 2 be reduced to provide a
To establish the physiological basis of the profiles of cardiopulmonary system responses component of respiratory compensation
to incremental exercise performed to the limit of tolerance. which constrains the fall of arterial pH.
To recognise when the value of a particular variable or its response profile reflects an The pulmonary system is therefore confron-
abnormality of system(s) functioning, both with respect to ted by different demands for blood-gas and
(a) the work rate itself or to other related variables and acid-base regulation during exercise. There
(b) consideration of responses that are often misrepresented as reflecting systems are competing ventilatory demands for alve-
behaviour. olar PO2 and PCO2 regulation when the re-
spiratory exchange ratio differs from unity,
2. Introduction
Introduction and also for arterial PCO2 and pH regulation
The tolerable range of work rates in patients with lung disease is constrained by a com- when the exercise results in a metabolic aci-
bination of factors, chief of which are: dosis. In patients with lung disease, this pro-
cess is further complicated by pulmonary gas
a) impaired pulmonary-mechanical and gas exchange function which increases the de-
exchange inefficiencies which result in of-
mand for airflow and ventilation;
ten-marked differences between alveolar
b) limitations in response capabilities, either of airflow generation or of lung distensi- (either ëidealí or ërealí) and arterial gas par-
on; tial pressures. Consequently, the impaired
c) increased physiological costs of meeting the ventilatory responses, in terms of respi- pulmonary gas exchange in patients with
ratory muscle work, blood flow and O2 consumption; chronic lung disease further increases the
d) predisposition to 'shortness of breath' or 'dyspnoea' as a consequence of the high ventilatory demand during exercise; the im-
fraction of the achievable ventilation demanded by the work rate, commonly exacer- paired pulmonary mechanics, however, cons-
bated by arterial hypoxaemia; and trains or even limits the ability to meet the
demands.
e) the often-marked reduction in the range of spontaneously-selected daily activities,
which results from the dyspnoea, and further reduces the state of physical training.

VIASYS info Special Edition CPET, April 2002 3

Essay
"The challenge is to select exercise tes-
ting procedures that optimize the stress
profile..."
3. Exercise Testing
Exercise
The principle that underlies strategies of
clinical exercise testing is that system failure
typically occurs while the system is under
stress. The challenge is to select exercise
testing procedures that optimize the stress
profile. A major objective of exercise testing,
therefore, is to observe the patient and make
measurements of ventilation and gas
exchange to distinguish among the
pathophysiological mechanisms causing
dyspnoea and exercise intolerance. A wide
variety of tests are available, each being more
or less suitable as a stressor of a particular
component of the patientís pathophysiology.
However, the appropriateness of the
integrated systemic responses is best studied
(at least, for the initial exercise evaluation)
by means of an incremental test, as this
provides a smooth gradational stress which
spans the entire tolerance range.
4. Exercise Tolerance and Exer
Exercise cise
Exercise
Intensity
While the tolerable duration of a given work
rate is known to depend upon the intensity
of the exercise being performed, there is to
date no generally-agreed scheme for charac-
terizing work intensity. Two widely-used pro-
cedures fail to meet the demands of critical
scrutiny in this regard: the "met" increment
and the "percentage" of the maximal O2
uptake (V'O2max). The onset of the metabo-
lic (lactic) acidaemia of exercise (i.e. the lac-
tate threshold ATL) does not occur at a com-
mon "met" increment in different individu-
als. Consequently, different subjects at the
same "met" level can have markedly diffe-
rent degrees of metabolic acidaemia. Simi-
larly, while in normal individuals ATL oc-
curs at approximately 50% of V'O2 max, the
distribution is very large, with the normal
range extending from 35% to at least 80%.
Consequently, if the exercise intensity is as-
signed to a particular percentage of V'O2 max
(e.g. 70%), then one subject could be exerci-
sing at a sub-ATL) work rate and be "com-
fortable" whereas another could exhaust at
V'O2 max.
Often, however, patients may not be able to
attain a V'O2 max in the conventional sense
(or the investigator may not wish to stress
them to these levels) because of limitation
by some system-related perception (e.g. an-
gina, dyspnoea, claudicating pain).
"A
"ATTL has proven to be a useful index of
the onset of an exercise-induced meta-
bolic acidaemia..."
4 VIASYS info Special Edition CPET, April 2002
However, as ATL estimation does not require
such efforts, it therefore provides:
a) an index of the functional status of the
respiratory-circulatory-metabolic inte-
gration that allows exercise to be
sustained aerobically;
b) an index of sustainability for a particular
task;
c) a frame of reference for optimizing train-
ing protocols;
d) an index of the efficacy of physical train-
ing, rehabilitation and drug interventions;
and
e) an essential component of decision-mak-
ing strategies for elucidating the domi-
nant system(s) responsible for exertional
dyspnoea and exercise intolerance.
"There is no generally-agreed upon pro-
cedure for normalizing work intensity..."
intensity..."
Therefore ATL has proven to be a useful in-
dex of the onset of an exercise-induced me-
tabolic acidaemia. One can forego the neces-
sity for serial blood sampling and even, in
many cases, enhance the discriminability of
ATL by utilizing a particular cluster of venti-
latory and pulmonary gas-exchange, which
provides noninvasive estimation of ATL. ATL
discriminability, however, under "complica-
ting" conditions such as chronic hyperventi-
lation syndromes, progressive exercise-in-
duced hypoxaemia, or impaired peripheral
chemosensitivity with an associated high air-
way resistance, for example, remain to be es-
tablished.
Although there is no generally-agreed upon
procedure for normalizing work intensity,
most would concede that moderate exercise
may be sustained for long periods but heavy
or severe exercise may not. The measured or
appropriately-estimated degree of metabolic
acidaemia can be used as a defensible index
of exercise intensity.
That is, three intensity domains may usefully
be identified:
a) moderate - work rates below ATL, with
no increase in arterial blood [lactate] or
[H+] and steady states of ventilation and
pulmonary gas exchange being achiev-
able;
b) heavy - that range of work rates above
ATL, for which [lactate] and [H+] are ele-
vated, and can achieve a steady state;
and
c) severe - even higher work rates, for which
[lactate] and [H+] increase inexorably
throughout the test, and steady states of
ventilation and gas exchange are not
achieved, V'O2 being set on a trajectory
to V'O2 max.
5. Test Design
The appropriateness of the integrated syste-
mic responses to the tolerable range of work
rates are best studied utilizing incremental
exercise testing, as this allows:
a) determination of whether the pattern of
response of particular variables is nor-
mal with respect to other variables or to
work rate;
b) the establishment of a subjectís limiting
or maximum attainable value for physi-
ological variables of interest; and
c) the establishment of exercise intensity
domains, such as the transition between
moderate and heavy intensity exercise.
It does this by providing a progressive,
gradational stress that spans the tolerab-
le work rate range. This minimizes or ob-
viates the effects of sudden and large in-
crements (that would be less well tolera-
ted by many patients).
Although exercise testing should ideally be
task-specific, laboratory exercise testing is
usually confined to treadmill and cycle-
ergometer exercise. Regular and accurate
calibration is important. The motor-driven
treadmill imposes progressively increasing
stress through various combinations of speed
and grade incrementation. An advantage of
the treadmill over the cycle ergometer is the
recruitment of a larger muscle mass which
causes more marked system stress, with
V'O2max being some 5-10% higher than for
the cycle ergometer. A major disadvantage
of the treadmill is the difficulty of accurately
quantifying the power. This reflects the
difficulty of providing a metabolic equivalent
of the grade and speed profile, coupled with
individual variations in body weight, walking
efficiency, pacing strategy and the
contribution from holding on to the treadmill
handrails. These factors can substantially

modify the metabolic rate up to an
unpredictable degree.
"Electronically-braked cycle ergometry
with a reasonable constant pedaling fre-
quency is recommended..."
The cycle ergometer has several advantages:
lower cost, less space, less prone to move-
ment artifacts, and more accurate quantifi-
cation of power. A variable contribution to
the oxygen cost of cycling at unloaded pe-
daling; i.e. largely a function of the weight
of the legs. However, if the pedaling cadence
remains essentially constant throughout the
test, this amount becomes a constant for all
work rates and therefore does not influence
the oxygen cost associated with a particular
work-rate increment. Electrically-braked cy-
cle ergometers are becoming increasingly
popular, although the older friction- braked
versions are adequate (recalling, of course,
that the power depends on the pedaling rate).
The electrically-braked models have the con-
siderable advantage that power is indepen-
dent of pedaling frequency, typically over
quite a wide range, and that work rate cont-
rol can be implemented remotely by a com-
puter.
Technological advances have made it
possible for sufficient density of data for
rigorous response-profile discrimination to
be acquired in a test lasting less than 20 min.
Such a test should include the following
phases:
a) rest
b) at least 3 min. of unloaded exercise
c) incremental exercise (~10-12 min), and
d) a recovery period
Electronically-braked cycle ergometry with
a reasonably constant pedaling frequency
(e.g. 60 rpm) is recommended. Essentially
similar results are obtained when work rate
is either increased continuously (ramp test)
or by a uniform small amount at regular short
intervals (e.g. one-minute incremental test)
until the patient can no longer sustain the
work rate (e.g. he/she cannot cycle > 40 rpm)
or is not able to continue safely. The
increment size should be set according to the
physical capabilities of the subject, to ensure
an incremental phase of ~10-12 min; this
corresponds to an incrementation rate of ~10
to 20 W/min for a healthy sedentary subject,
but as little as 5 W/min in a patient. However,
further modifications to the protocol design
of the protocol may be necessary if, for
example, the subject is severely debilitated
or is highly fit. Slower rates of change, in
addition to inducing boredom and seat
discomfort, also reduce the ability to
VIASYS info Special Edition CPET, April 2002
discriminate threshold behavior. More rapid
rates of change impose greater strength
demands, and introduce complexities of
threshold discrimination resulting from
transients of CO2 stores wash-in.
A range of protocols are available for
treadmill testing. However, the
recommendation is for tests that increment
the work rate at constant rate, with small
increments providing the best discrimination.
It is preferable to employ increments in
treadmill grade at a constant speed.
After an incremental test has been performed,
there are circumstances in which the
investigator may wish to conduct constant-
load testing in order to gain additional
information about system response kinetics
in different intensity domains. Such
additional tests should, of course, be
performed on separate occasions.
6. Formatting the Outputs
Having performed such a test appropriately,
the investigator then needs to format the
results in a manner that optimizes the ability
to discriminate essential response features;
i.e. to establish "interpretive clusters" of the
variables of interest. The challenge in
assessing the normalcy, or otherwise, of the
system responses to the exercise is to select
the appropriate response variables that are
themselves reflective of the particular
system(s) behavior and to display their
profiles of response either as a function of
work rate or within the context of the
response of a related physiological variables.
That is, what the response of a particular
variable means and, often as importantly,
what it does not mean.
7. Useful Noninvasive Responses
VO2-WR rrelationship
elationship
In response to a constant work rate challenge,
V'O2 increases exponentially to attain a stea-
dy state (over the work rate range for which
steady states are attainable). The magnitude
of the steady-state increase in V'O2 as func-
tion of the work rate increment (i.e.DV'O2/
DWR) is considered to be the functional sys-
tem "gain" (functional is used here as purists
insist that gain has no units). This gain is
functionally the inverse of the work efficien-
cy, the difference being that in the efficiency
computation DV'O2 is transformed into its
energy equivalent by taking into account the
substrate mixture undergoing oxidation, i.e.
the gain is higher for fatty acid oxidation than
for carbohydrate whereas the actual work
efficiency is not different.
Essay
"For incremental exercise tests of the
ramp type, a constant rate of change of
WR replaces the constant absolute WR as
the challenge..."
For incremental exercise tests of the ramp
type, a constant rate of change of WR re-
places the constant absolute WR as the chal-
lenge. Consequently, this yields a constant
rate of change of (i.e. linear with respect to
time and therefore WR) after a small lag-
phase which reflects the system response ki-
netics.
The O2 gain has been shown (at least in
healthy subjects) not to differ from that of
the steady-state response (normally 9-11 ml/
min/Watt). The value of V'O2 at any work
rate on a ramp test is therefore lower than
that for the steady state at that work rate, al-
though its rate of change is normally the
same. The incremental gain is therefore of-
ten used as an index of the work efficiency.
However, in many patients with cardiopul-
monary diseases, this incremental gain can
be very low (e.g. 8 ml/min/Watt or less). This
may be interpreted in one of two ways:
(a) The intramuscular energy transduction
mechanisms linking ATP production to
oxygen utilization have become Ñhyper-
efficientì (an unlikely scenario) or
(b) that unlike healthy subjects, the time con-
stant of response is not a constant irres-
pective of WR but rather may lengthen
as WR increases. Remarkably, to date,
the criteria that justify the incremental
gain as being reflective of the steady-state
gain have never been established, except
in healthy subjects.
The highest value achieved with good sub-
ject effort is termed the "PeakV'O 2
(VO2peak). In those instances in which V'O2
does not continue to increase with further
increases in WR (i.e. a plateauing results)
yields what is termed the maximal V'O2
(V'O2max). Plateaux of V'O2, however, seem
not to be common, such that without evidence
from other tests that the highest attained
meets the original criterion for V'O2 max, the
value should be reported as V'O2 peak. It is
important to recognise, however, that while
V'O2 max is not different with different ramp
slopes the maximum work rate attained is
progressively greater the faster the ramp.
"... the pattern of the VCO2-VO2 relati-
onship is highly dependent upon the rate
at which the WR is incremented..."
5
Essay
VCO2-VO2 relationship
The profile of pulmonary CO 2 output
(V'CO2) as a function of V'O2 during incre-
mental exercise is dependent upon two fac-
tors:
the substrate mixture undergoing oxida-
tion (i.e. the RQ effect) and
the CO2 storage into from muscle and
blood (i.e. the factor that causes RER to
differ from RQ).
Consequently, the pattern of the VCO2-VO2-
relationship is highly dependent upon the rate
at which the WR is incremented.
The typical pattern, however, is one in which
the V'CO2 response initially lags that of V'O2
early in the transient and then increases of-
ten as a linear function of V'O2. The slope
of the relationship (DV'CO2/DV'O2) in this
region has been termed S1, with a value typi-
cally close to unity in subjects on typical
western diet - but can be greater than 1, even
without hyperventilation!
The slope of the V'CO2-V'O2 relationship
increases at a particular V'O2 as the aerobi-
cally produced CO 2 released from
bicarbonate buffering of protons associated
with lactate accumulation. The slope in this
higher WR region has been termed S2, and
as the amount of CO2 released in the proton
buffering process is a function not of the
magnitude of [bicarbonate] decrease but its
rate of decrease, this slope is highly depen-
dent on the WR incrementation rate. Furt-
hermore, at slow WR incrementation rates,
additional CO2 from compensatory hyperven-
tilation supplements the V'CO2 in the S2 ran-
ge; this is not the case for rapid incrementa-
tion rates, for reasons not fully understood.
Maximum RER, being so dependent on the
ramp slope is consequently not a good index
of subject "effort".
The S1-S2 transition reflects a metabolic rate
above which CO2 is released from the body
that does not originate in either aerobic me-
tabolism or hyperventilation. And as bicar-
bonate is clearly the origin of this extra CO2,
and the [bicarbonate] change is a close pro-
portional function of the increase in muscle
[lactate], this is considered to be a valid non-
invasive index of the lactate (or anaerobic)
threshold. When the V-slope plot may not be
partitioned into two defensibly-linear seg-
ments the unit tangent to the curve may be
used as a second order estimate of the lactate
threshold.
"...a high VD/V T does not necessarily re-
flect abnormal pulmonary function, as it
is highly dependent on the pattern of
breathing..."
6 VIASYS info Special Edition CPET, April 2002
V'E-V'CO2 relationship and ventilatory
equivalents
The ventilatory (V'E) response to exercise as
a function of V'CO2 is fundamentally related
to the regulation of arterial PCO2 (PaCO2)
and pH.
For alveolar ventilation (V'E) the relationship
is:
V'A= 863 x VCO2 /PaCO2
Consequently, to regulate PaCO2, V'A must
change as an appropriate linear function of
V'CO2. However, with respect to total venti-
lation (i.e. V'E) the relationship is complicated
by the ventilation of the physiological dead
space or by the dead space fraction of the
breath (VD/VT) such that:
V'E= 863 x VCO2 /[PaCO2 (1 - VD/VT)]
High values of V'E/V'CO2 therefore reflect
either a low PaCO2, high VD/VT or both. Nat-
urally, if one is known or may be plausibly
assumed, then the high V'E/V'CO2 may be in-
terpreted in terms of the other.
It should be noted, however, that a high VD/
VT does not necessarily reflect abnormal pul-
monary function, as it is highly dependent
on the pattern of breathing: rapid, shallow
breathing, for example, yields a high VD/VT
even in subjects with normal pulmonary
function.
V'E has been widely demonstrated to change
as a linear function of over a wide range of
WRs, i.e.: V'E = mV'CO2 + c
Different investigators use different aspects
of these latter equations to characterise the
ventilatory response:
a) the ratio V'E/ V'CO2 and
b) DV'E/DV'CO2 (i.e. m).
Clearly, V'E/V'CO2 is important, as it is in-
fluenced only by VD/VT and PaCO2. Note that
in cases in which PaCO2 is constant, VE/
V'CO2 falls in exact proportion to that of VD/
VT. Interestingly, the constant m can be defi-
ned as:
m =V'E /V'CO2 - c/V'CO2
That is, m may be considered to be the
asymptote of the decliningV'E/V'CO2-profi-
le; not necessarily its lowest value achieved
during the test. Alternatively, V'E/V'CO2 may
be considered to decline during exercise as a
result of the positive intercept c. For rapid-
incremental tests, interestingly, the linearity
of the V'E-V'CO2 relationship is maintained
beyond the lactate threshold; i.e. V'E chan-
ges in proportion to the total CO2 load, with
no evidence of PaCO2 being reduced to pro-
vide respiratory compensation (isocapnic
buffering). The respiratory compensation
begins at higher WR, when both V'E/V'CO2
and m begin to increase.
"End-tidal gas tensions are easy to measu-
re and extremely dif ficult to interpret..."
difficult
As V'E is so closely linked to V'CO2 and as
V'CO2 varies markedly with the WR incre-
mentation rate, V'E does not change in a use-
fully-constant relationship to V'O2, and hence
is rarely used in this context. The ratio V'E/
V'O2 however, is used as an index of the ad-
ditional ventilatory drive that attends the ac-
celerated CO2 output at work rates above the
lactate threshold. Having declined throug-
hout the moderate work-rate range, V'E/VO2
begins to increase reflective of increased
V'CO2, and when coupled with V'E/VO2 not
increasing (i.e. isocapnic buffering) provides
good support that the increased ventilatory
drive is not consequent to hyperventilation -
in which case both V'E/V'O2 and V'E/VCO2
and the slope of the V'CO2- V'O2 relations-
hip increases.
End-tidal gas tensions
End-tidal gas tensions, i.e. the values deter-
mined at the end of an exhalation, are easy
to measure and extremely difficult to inter-
pret. During exhalation, alveolar PCO 2
(PACO2) continues to increase at a rate that is
dependent on the mixed venous PCO2 value
and to a level that depends on the duration
of the exhalation; The end-tidal value being
greater than the mean alveolar and arterial
value, as work rate increases in normal sub-
jects is therefore entirely to be expected.
The end-tidal to mean alveolar PCO2 diffe-
rence continues to increase as WR and there-
fore increases, but can then stabilise at WRs
at which tidal volume ceases to continue to
increase with respect to V'CO2, and breathing
frequency therefore accelerates, progressi-
vely to shorten expiratory duration. PETCO2
may therefore be considered to be the peak
of the oscillation of PACO2 during the brea-
thing cycle.
In the "ideal" lung, "arterial" blood will also
manifest such an oscillation, but this
oscillation is not measured: what is measured
is the mean of this oscillation in PaCO2, as
blood is sampled over several respiratory
cycles. Mean PaCO2, however, differs from
mean PACO2 as a result of ventilation-to-
perfusion inhomogeneities and/or right-to-
left shunt - leading to P ET CO 2 being
commonly less than PaCO2 in patients with
COPD for example. Consequently, PETCO2
equal to or less than mean PaCO2 during
exercise is reflective of abnormal gas
exchange.

"In the "ideal" lung, arterial blood will
also manifest such an oscillation, but this
oscillation is not measured..."
End-tidal PCO2 should therefore not be used
to represent arterial PCO2 in computing VD/
VT. Doing so overestimates VD/VT in normal
subjects (tending to make abnormal what is
normal) and underestimates it in patients with
lung disease (tending to make normal what
is abnormal). Algorithms for estimating
PaCO2 from PETCO2 are poor in normal sub-
jects and do not work in subjects with lung
disease.
Consequently, the profile of PETCO2 with
increasing WR is normally such that it
increases progressively up to the lactate
threshold, then stabilizes in the region of
isocapnic buffering, and subsequently
decreases as frank compensatory hyper-
ventilation is manifest. In contrast, end-tidal
PO2 (PETO2) progressively decreases up to the
lactate threshold, after which it increases
systematically, accelerating further with the
onset of compensatory hyperventilation.
VO2 heart rate relationship and
oxygen pulse
The oxygen pulse, or the stroke extraction
of oxygen (V'O2/HR) bears a similar relation-
ship to the V'O2/HR-slope as the ventilatory
equivalent for CO2 does with the V'E/V'CO2-
Slope. That is, heart rate changes effectively
linearly as a function of V'O2 with a slope
that is an inverse function a physical fitness.
It is instructive to consider the axes diffe-
rently however: that is, plotted as function
of heart rate. This relationship has a negati-
ve intercept on axis. Consequently, the oxy-
gen pulse, which by definition is the absolu-
te VO2to heart rate ratio increases hyperbo-
lically as work rate increases.
But the oxygen pulse is of interest in an ad-
ditional sense: it is numerically equivalent
to the product of stroke volume and the arte-
rio-venous oxygen content difference. It is
important to point out, however, that it should
not be considered a function of either of these
variables - only the product. Consequently,
only if it is possible to make a reasonable
assumption regarding the change (or not) in
either of the two defining variables may one
interpret the non-invasive O2 pulse profile
to reflect that of the alternative variable. This,
of course, would be both more difficult to
determine directly and would require an in-
vasive procedure.
"Subjects who are normal but unfit have
a shallow slope of V'O2 plotted as a func-
tion of heart rate..."
VIASYS info Special Edition CPET, April 2002
Essay
If the O2 pulse fails to increase with increas- considered to represent the subjectís
ing work rates, then the product of the vari- breathing reserve (BR). The breathing reserve
ables is constant. But this may be because can be zero (or even less than zero, for
each is constant or one is increasing while example, in a subject who bronchodilates
the other decreases. Flatness in the O2 pulse during exercise) either as a result of the MVV
profile should be considered with care, ho- being low, as in patients with lung disease,
wever, as subjects who are normal but unfit or in normal but highly fit subjects who can
have a shallow slope of V'O2 plotted as a achieve high rates of metabolic rate and
function of heart rate and hence the curvatu- hence of ventilation. Similarly if the
re of the O2 pulse profile will be shallow - maximum expiratory airflow produced with
appearing to be flat when in fact it is not. a maximum expiratory effort is considered
For the O2 pulse to be flat there must be a to reflect the greatest possible flow at a
change in the slope such that heart rate acce- particular lung volume (this of course is not
lerates relative to such that over this region necessarily the case in subjects with
the slope extrapolates back to the origin of obstructive lung disease) then failure to
the plot. When this does occur continued in- achieve these flows on a breath during
crease in is heart rate dependent. exercise is reflective of flow reserve.
Similarly, a tidal volume that encroaches
"...the oxygen pulse, which by definition upon the inspiratory capacity is reflective of
is the absolute VO2 heart rate ratio, incre- lack of volume reserve. Whether a subject
ases hyperbolically as work rate increa- has significant heart rate reserve at maximum
ses..." exercise is usually judged in the light of the
expected maximum value for a subject of that
age - unfortunately, the variability of this
8. Values attained at the limits of expected age-dependent maximum heart rate
tolerance is very wide.
When a subject has ostensibly exercised to
the limit of tolerance it is useful to discern
whether certain features of the systems that
contribute to the energy exchange have
reached their limit. Naturally to make this
judgement it is necessary to have an index
of what that limit is. For example, if the MVV
determined at rest is considered to be the
maximum ventilation attainable then the
difference between this and the value actually
attained at the end of exercise can be
References
References
Gallagher,, C. Exercise and chronic obstructive pulmonary disease. Med. Clinics N. Am. 74:619-
1. Gallagher
641, 1990.
2. Hadebank, D., Reindl, I., Vietzke G., et al. Ventilatory efficiency and exercise tolerance in
101 health volunteers. Eur J Appl Physiol 77:421-426, 1998.
3. Johnson, B.D., Badr
Badr,, M.S., Dempsey
Dempsey,, J.A. Impact of the aging pulmonary system on the re-
sponse to exercise. Clin Chest Med 15:229-246, 1994.
4. Jones, N.L. Exercise testing in pulmonary evaluation: Rationale, methods, and the normal
respiratory response to exercise. New Engl. J. Med. 293:541-544, 1975.
5. Neder
Neder,, J.A., L.E. Ner
Neryy, C. Peres, and B.J. Whipp. Reference values for dynamic responses to
Peres,
incremental cycle ergometry in males and females aged 20 to 80. Am. J. Respir. Crit. Care Med.
164:1481-1486, 2001.
6. Roca, J., Whipp, B.J. (eds): Clinical Exercise Testing. European Respiratory Monograph vol
2, No 6. Sheffield: European Respiratory Journals, 1997.
7. Rowell, L.B., Shepherd, J.T
J.T.. (eds). Handbook of Physiology, Sect 12, Exercise: Regulation
and Integration of Multiple Systems. New York: Oxford Univ Press, 1996.
8. Wagner
agner,, P.D. Determinants of maximal oxygen transport and utilization. Ann Rev Physiol 58:21-
P.D.
50, 1996.
9. Wasserman, K., Hansen, J.E., Sue, D.Y ., Casaburi, R, Whipp, B.J. Principles of exercise
D.Y.,
testing and interpretation. Philadelphia, Lippincott, Williams & Wilkins, 1999.
10. Weisman, M., Zeballos, R.J. Clinics in Chest Medicine. Saunders, 1994.
7
Applications

CPET - VVarious
arious Fields of Application
Indication and relevance of cardiopulmonary
exercise testing
Definition: Cardiopulmonary Kardiologie
exercise testing is defined as the
continuous measurement of respi-
Estimated oxygen uptake during different
ratory gases during exercise. activities and occupations:
Intr oduction
Introduction [ml/kg/min]
CPET is a diagnostic procedure that analyz-
Work, sitting 4,25
es the response and cooperation of the heart,
Driving a car 4,25
circulation, respiration and metabolism dur-
Driving a truck 5,30
ing continuously increasing muscular strain.
Work, standing 8,75
In this way, maximum exercise capacity and
Walking (4.5 km/h) 10,50
the endurance capacity threshold can be de-
Crane operating 8,75
tected. These parameters are of special im-
Cleaning the floor 9,45
portance in the fields of:
Light warehouse work 10,50
Painting, wall paper hanging 14,00
Pulmonology
Bricklaying, carpentry 14,00 - 21,00
Cardiology Working with Jack hammer 21,00
Steel worker 27,00
Sports medicine
Occupational medicine
Intensive care
Rehabilitation
If exercise capacity is limited, the character-
istic patterns of the parameters provide im-
portant information about which organs are
affected by the impairment.
As testing sytems become more and more
user-friendly, the interest in comprehensive
cardiopulmonary exercise testing is contin- During cardiopulmonary exercise testing the Four basic parameters will be rrecorded
ecorded
uously increasing. Due to the variety of pa- subject is placed either on an ergometric bi- with the help of a br eathing mask and
breathing
rameters provided, the fields of application cycle or treadmill where load can be contin- ECG electr odes:
electrodes:
are widely distributed. uously increased. Minute ventilation
If an organ or an organic system is impaired, The complex requirements of cardiopulmo- Oxygen uptake
the subjects' ability to adjust to increasing nary exercise testing are met by ramp proto-
Carbon dioxide output
strain is impaired. cols. During this type of test, strain is in-
creased in small increments. The duration of Heart rate (stress ECG)
the test should be between 8 to 12 minutes.
For a complete analysis of respiratory func- Prior to CPET the following should be
tion, the flow-volume curve should be re- completed:
corded at rest, prior to exercise and during
submaximal and maximal exercise. The same Patient history
applies to blood gas values and P(A-a)O2. ECG at rest
To clarify special questions concerning gas Pulmonary function test
exchange (for example diffusion disorders),
a constant workload test below anaerobic
threshold including blood gas analysis may
be performed.
Exercise should be symptom-optimized,
whereby the usual termination criteria for
exercise tests have to be observed.

8 VIASYS info Special Edition CPET, April 2002


Pneumology
Obstructive and restrictive ventila-
tory disorders
Interstitial disorders
Pulmonary hypertension
Diffusion and distribution
disorders
Flow disorders
Stress dyspnea of unknown
cause
Suspected limited exercise capa-
city due to circulatory or pulmona-
ry disorders
Suspected exercise-induced asth-
ma
Trend control in presence of re-
spiratory and pulmonary diseases
Risk estimation for lung transplant
patients
Applications of CPET
During CPET the following paramters can
be rrecorded:
ecorded:
Maximum oxygen uptake (peak VO2)
Oxygen uptake at anaerobic threshold
(VO2AT)
Oxygen pulse (O2 Pulse)
Breathing equivalents (EQO2, EQCO2)
Dead space ventilation (VD/VT)
Aerobic capacity (dVO2/dWR)
Alveolar-arterial oygen pressure diffe-
rence (P(A-a)O2)
Respiratory exchange ratio (RER)
Work rate (watts)
Heart rate reserve (HRR)
Breathing reserve (BR)
VIASYS info Special Edition CPET, April 2002
Cardiology
Coronary heart disease
Cardiomyopathy
Valvular heart disease
Congenital cardiac defects
Risk estimation for heart trans-
plant patients
Cardiac insufficiency
Sports Medicine
Measurement of physical perfor-
mance for effective training adjus-
tment
Quantification of an increase in
performance
Curve analysis
In addition to the assessment of the achieved
maximum values, the curve trends of the in-
dividual parameters have to be assessed over
the entire exercise test. Modern CPET sys-
tems with breath by breath analysis (such as
the Jaeger Oxycon series) allow for a high
resolution of the individual parameters. On
the basis of the nine panel graph, deviations
of the expected curve trend can be easily as-
sessed. Depending on the limiting clinical
picture, typical changes are to be expected.
On-line recording of the flow-volume curves
during exercise is also very helpful. By su-
perimposing the maximal envelope and the
current flow curve, the impairment is re-
vealed in the form of a volume or flow limi-
tation.
Fig. left:
9-panel graph
Application
Occupational Medicine
Determination of occupational
exercise tolerance
Determining the degree of disabi-
lity or work limitation/inability
Fitness checkups (high altitude,
air travel, tropical climate, diving)
Intensive Care
Risk assessment prior to
surgery
Nutrition control (adjusting paren-
teral nutrition of intensive care
patients)
Rehabilitation
To optimize rehabilitative mea-
sures
To assess and document rehabili-
tative and therapeutic progress
Documentation
Comprehensive and reproducible documen-
tation of the exercise test is indispensable.
Test type and load protocol, as well as an
assessment of the achieved capacity accord-
ing to clinical criteria, should be document-
ed independently of the achieved measured
values. At the end of the test the subject
should be interviewed on the basis of the
Borg scale. This simplifies interpretation of
examination results, especially if measured
values suddenly differ greatly.
Fig. right:
Intrabreath
9
Diagnostics

Oxycon PPro
ro - CPET of the Highest Quality

A modern diagnostic system must not only be techni-

cally convincing, it must above all, be tailored to the
routine clinical needs. Therefore, we made Oxycon
Pro even faster, more precise and above all, even
more economic. For your daily routine you need a
practical tool which is suitable for its tasks. After all,
you prefer to give attention to your patients and not to
your equipment. That is why Jaeger developed the
Oxycon Pro.

Oxycon is your expert system if you need a Integrated PC-based ECG:

favorably priced CPET system including ECG All data at a glance:
recording at rest and during exercise.
A notable feature of Oxycon Pro is the ex-
Oxycon Pro precisely analyzes, differentiates
ceptional stability of the stress ECG baseline
and quantifies the functional cooperation of
Oxycon Pro is the perfect solution for routine traces. 12-channel ST monitoring is based on
heart, lungs, circulation and metabolism.
cardiopulmonary exercise testing. The small a 10-second-interval. A clearly structured ST
Oxycon Pro is a secure investment for physi-
handy unit combines everything required for graph displays the ST changes in different
cians working in the fields of cardiology, oc-
routine examinations and offers unparalleled color. In addition, automatic arrythmia detec-
cupational medicine, pediatrics, pulmonology
ease of operation. And as costs are an impor- tion is provided.
and intensive care. It is the ideal system for
tant factor in modern day medicine, Oxycon
the secure assessment of physical perfor-
Pro is favorably priced and meets the highest
mance.
quality standards. The modular concept pro-
vides sufficient possibilities for upgrades or
subsequent expansion, whenever required or
your investment policies allow it.
The heart of the Oxycon Pro is its precise
and reliable ergospirometry measurement pro-
gram. Ergospirometry and related parameters
can either be measured "Breath by Breath",
"Intrabreath" or via the mixing chamber.
User-specific work load protocols for exer-
cise on bicycle or treadmill guide you through
the test. The screen display is clearly struc-
tured. Preset and logically arranged graphs
and groups of graphs show the status of the
current workload phase with predicted/actual
value comparison.

Fig. above: 12-channel ECG including ergospirometry data

10 VIASYS info Special Edition CPET, April 2002

 Diagnostics

Oxycon Pro
Oxycon Pro

O2/CO2-analyzer z
Digital volume sensor (TripleV) z
Pentium PC z
Ink-jet printer z
Trolley {
Standard programs:
Patient data z
Automatic volume calibration z
Volume calibration via manual cal. pump {
Automatic gas analyzer calibration z
Ambient conditions z
Spirometry/Flow-Volume z
Off-line blood gases/lactate z
Ergospirometry data during testing - clear and easy Breath by Breath z
Intrabreath z
Mixing chamber {
High/Low FiO2 {
The advantages of Oxycon Pro:
Pro: Indirect calorimetry z
- Hood {
Windows-based user interface - Ventilator {
Automatic calibration programs - Hood with high FiO2 {
Fast and highly precise gas analyzers - Hood for children {
Precise, low-resistance volume sensor, Cardiac output {
no flow limitation in the physiological Compliance during exercise {
range P0.1 during exercise {
Standard measurement programs: Resting and stress ECG {
Spirometry/Flow-Volume Screen and printer report z
Interpretation program:
Breath by Breath, Intrabreath
(partial Flow-Volume loop) IntelliSupport z
Generation programs:
Indirect calorimetry
ReportDesigner z
Integrated, optional paper-free Oxycon Pro on trolley Layout editor z
12 channel ECG
Profile editor z
Interpretation program
Parameter text editor z
ÑIntelliSupportì
LaguageMaker z
Informative, detailed reports User predicted values z
All components available from Predicted value generation z
JAEGER Other programs:
Modular concept Data base z
Interfaces for stress-testing devices Load control z
and other systems, for example, Connection to practice/hospital EDP syst. {
external ECG ECG suction device {
Data management for practice Pulse oximeter {
administration systems and for
hospital networks
z Standard
{ Option

VIASYS info Special Edition CPET, April 2002 11

Practical Guideline

Cardiopulmonary Exercise TTesting

esting
Author: W. Mitlehner M.D.
Authorized translation from German

Exercise testing and ECG recording have been known for about 60 years (1, 2) and have meanwhile been
standardized. The goal of this routine test is to detect coronary heart disease. More than 70 years ago, A.V.
Hill was the first researcher to examine gas exchange and acid-base-metabolism during exercise while
studying muscular physiology (3). During the 1940's, a precise method for testing gas exchange (oxygen
uptake and carbon dioxide release) was established for the first time by P.F. Scholander (4). During the
1950's, cardiopulmonary exercise testing had been applied in clinical examinations of patients with cardiac
diseases (5, 6). A non-invasive stress testing procedure was hence established that allowed recording of
cardio-circulatory and ventilatory, as well as "peripheral" parameters during exercise in addition to elec-
trocardiographic changes. However, a great deal of experimental methods were required making the proce-
dure not clinically feasible. It were Issekutz and Rohdahl, (7) as well as Wasserman et al., (8) who finally
developed a method to reliably record oxygen uptake (V'O2) and carbon dioxide release (V'CO2) with the
help of fast gas analyzers on a breath-by-breath basis.

Introduction to CPET
Introduction
Computer technology and advancement of
the methods introduced more than 20 years
ago have made it possible to easily perform
reliable exercise tests, especially in the field
of cardiology and pneumolgy. The increasing
interest in this procedure caused us to com-
pile a practical and comprehensible introduc-
tion to CPET in healthy subjects and patients
with lung disease. Literature references can
be found at the end of this brochure.
Cardiopulmonary exercise testing can be de-
fined as "performance testing on the basis
of cardiac, circulatory and ventilatory para-
meters" for non-invasive quantification of a
subject's physical training limits.
In addition to determining a subject's exer-
cise capacity (e.g. sports medicine) the test
goals are to record the cause of a possible
performance impairment and to measure the
effect of therapeutic interventions.
Metabolic processes and life are only pos-
sible if energy is provided in the body cells.
At rest, this process takes place in the musc-
le cells where primarily glucose undergoes
aerobic metabolic processes in order to form
phosphates that are rich in energy (ATP).
During physical strain (under stress) ATP is
first formed aerobically. If stress increases,
ATP is increasingly produced anaerobically
by glycolysis. This process, which is known
as cellular respiration, requires oxygen and
substrates that are rich in energy (primarily
glucose) and forms carbon dioxide as a final
product as well as pyruvate and lactate as an
anaerobic intermediate product.
Thanks to cardiopulmonary exercise testing,
it is possible to quantify a subject's oxygen
uptake (VíO2) and carbon dioxide release
(VíCO2) and can indirectly observe vesicu-
lar breathing in humans and consequently
cellular respiration.
Due to adequate ventilation (VíE), the brea-
thing mechanism allows for gas exchange
(VíO2 and VíCO2) which provides the mus-
cles with oxygen (DíO2) and assures that car-
bon dioxide be transported off (DíCO 2 )
bridged by the cardiovascular system (car-
diac output). Coupling the processes of cel-
lular respiration, the cardiovascular system
and ventilation are regulated as required ac-
cording to the blood- and tissue-homeosta-
sis rules for pH, oxygen and carbon dioxide
content by central and peripheral regulatory
mechanisms. These control mechanisms are
responsible for the interaction between these
three systems so that the increasing metabo-
lic requirements in the cells under stress can
be met. Sufficient oxygen flow to the cells
and blood gas homeostasis (pH) in increa-
sed carbon dioxide generation through phy-
sical activity are regulated as needed. If one
of the systems is disturbed (peripheral, car-
diovascular, pulmonary or central regula-
tion), considerable changes occur which can
be quantified during cardiopulmonary exer-
cise testing.
As we will later see, the test results are high-
ly reproducible. Consequently, this method
is especially suited:
1. to determine the severity of a perfor
perfor--
mance limitation with rrespect
espect to rrepr
epr o-
epro-
ducibility (for approaches in cardiology,
pulmonology and assessments)
2. to define the ef
effect inter--
fect of therapeutic inter
ventions in the presence of exercise limi-
tation
supportt in dif
3. to provide suppor fer
differ ential diag-
ferential
nosis regarding the cause of exercise li-
mitation (cardiac, pulmonary or periphe-
ral).
Indications for peforming cardiopulmona-
ry exercise testing (T
exercise ab. 1)
(Tab.
Sports medicine
As cardiopulmonary exercise testing mea-
sures a subject's exercise capacity, it is often
used to examine healthy subjects in the field
of sports medicine. In contrast to the stress
ECG, which is somewhat simpler, cardiopul-
monary exercise testing allows for the ob-
jective and non-invasive measurement of a
subject's cardiorespiratory performance and
of an athlete's anaerobic threshold. The re-
sults provide important information for train-
ing purposes. This method has been applied
for years (9) and is a routine measurement in
sports medicine (10).

12 VIASYS info Special Edition CPET, April 2002

 Practical Guideline

Cardiology Pulomonology the patient exercise to a maximum?") and an

In order to test the cardiorespiratory func-
tion in patient groups with cardiac diseases,
cardiopulmonary exercise testing is regarded
to be the best suited test (11) and should be
routinely performed in transplant patients
(11) to determine the severity of the limitati-
on and to give evidence of the failure of other
therapeutic interventions.
In patients with etiologically undefined stress
dyspnea, the test is extremely useful for dif-
ferentiating dyspnea with primarily pulmo-
nary cause from dyspnea with primarily car-
diac cause (12, 13, 14).
In the presence of restrictive and obstructive
ventilatory disorders and their different
causes, cardiorespiratory exercise testing is
suitable for characterizing the resulting
causes, such as limitation of breathing me-
chanics, peripheral deconditioning, gas ex-
change disorders and stress hypoxaemia. Si-
milarily, it is possible to objectively quan-
tify the effect of pharmocologic interventions
in both groups of patients as well as the suita-
bility of oxygen application (15, 16).
Last but not least, exercise testing is useful
in selecting patients for lung transplantation
and post-surgical rehabilitation (17).
objective measurement of his/her exercise ca-
pacity as well as the causes of a possible li-
mitation.
For both cardiological and pneumological as-
sessments specific scales are provided clas-
sifying the degree of limitation which are
based on cardiopulmonary exercise testing
(21, 22).
Rare approaches
Cardiopulmonary exercise testing has been
used to assess muscular diseases, neuromus-
cular diseases and hemoglobinopathy. The
rank of CPET, here, is not clearly defined.

Approach Application Value

Performance testing Sports medicine, A

Disability evaluations, Cardiology A
Pneumology A
Muscular and Neuromuscular Diseases C
Training recommendations Rehabilitation A
Undefined dyspnea Cardiology, Pneumology A
Disability Assessments A
Transplantation Cardiology, Pneumology A
Therapeutical intervention CMP, Cardiac Valve Defects, A
Oxygen Therapy, A
Interstitial Pulmonary Disease, A
Rehabilitation A
Table 1: Indications for CPET
Resection of lung tissue Pneumology B
Coronary heart disease Cardiology C Value:
CHD - ischemic left ventr. insuff. Cardiology A A = highly informative
B = informative
Pulmonary vascular disease Cardiology, Pneumology B C = less informative

Cardiac patients with therapeutic interven-
tions, the effect of which can be proved by
an increased performance, should always be
examined with the help of cardiopulmonary
exercise testing in order to get an objective
assessment (e.g. therapeutic interventions in
the presence of cardiomoyopathy, mitral
valve defects, pre and post heart transplan-
tations).
In the field of rehabilitation of patients with
cardiac diseases, the test is suitable for defin-
ing an adequate training program and objec-
tively assessing the effects of training (11).
Generally, the test can be used for routine
testing in cardiology, when performance ca-
pability is to be tested (11).
In pre-surgical examinations (resection of
lung tissue) exercise testing is suitable for
excluding post-surgical complications (18,
19).
Cardiology and Pulmonology
Exercise testing allows the observation of
cardiopulmonary interaction and is therefore
indispensable in defining the dominant cau-
se of undefined stress dyspnea (20, 11).
Disability evaluations
For disability evaluation, cardiopulmonary
exercise testing is of great importance. In
contrast to simple stress testing and "Oxyer-
gometry" cardiopulmonary exercise testing
provides both a score of the test quality (did
In a nutshell, we can say that cardiopulmo-
nary exercise testing can be used in many
internal medical fields. Among many known
methods, CPET is the most comprehensive
and most informative non-invasive method
and is likely to become the standard method
of routine exercise testing in the field of in-
ternal medicine.
"The physiological processes during exer-
cise are quite complex and of inter-
disciplinary character..."
character..."

VIASYS info Special Edition CPET, April 2002 13

Practical Guideline

Physiological Basics ATP consumption is regenerated by four Depending on their contractional and fatigue-
The physiological processes during exercise physiological mechanisms: induced behaviour, muscle fibers and rela-
are quite complex and of interdisciplinary aerobic respiratory chain phosphoryla- ted motoneurons can be physiologically dif-
character and can only be summarized in a tion ferentiated in S (= slow-fatigue-resistant), FR
very simplistic form. The author explicitly (= fast-fatigue-resistant), FI = (fast-fatigue-
anaerobic glycolysis
refers to the respective literature (e.g. 12, 23 intermediate) and FF (= fast fatigable) mo-
creatine kinasis tor units.
- 25, 31).
adenylate kinasis These motor units are closely related to his-
Physical exercise is physical work (= Power
x Distance = 1 kp x m). This work is On the basis of their myofibrillar ATPase ac- tochemical classification: the aerobic type I
measured in terms of performance quantities tivity, the voluntar
voluntary y muscles can be diffe- fibers are slow and fatigue-resistant (S),
(Performance = Work/Time unit = 1 kpm/ rentiated histochemically in different meta- whereas the anaerobic type IIb fibers are fast
min). Physiological performance is traditio- bolic and functional fiber portions: Type I, fatigable (FF). Types IIa and IIx are of inter-
nally given in watts (1 watt = 6,12 kpm/min). IIa, II b and IIx fibers. mediate character.
For muscle contraction during exercise, ad-
ditional energy above basal metabolic rate
must be provided by the metabolism.
The increased metabolic requirements are
met by increased fat or carbohydrate oxida-
tion (cellular respiration). The energy re-
leased by combustion can be defined in terms
of kilocalories (oxidation of 1 g fatty acid =
9 kcal; oxidation of 1 g carbohydrate = 4
kcal). RC
The increased oxygen demands during work
are met by external respiration (gas ex-
change) and by the cardiovascular system
(oxygen transportation). In the case of pure
carbohydrate combustion, the physiological
demands for oxygen can be calculated as fol-
lows: one liter O2 is required for generating
5,1 kcal (4,6 kcal in case of fatty acid oxi-
dation). Consequently, 1 l oxygen can pro-
duce an average of 5 kcal.
The carbon dioxide and bicarbonate (CO2, Fig. 1
HCO3), which is simultaneously released dur-
ing substrate combustion, considerably in- Type I fibers are especially rich in oxidative Under incremental exercise, recruitment of
fluence the pH value of the blood and are enzymes, whereas type IIb fibers contain the fibers takes place as follows: S fibers with
released into the environment via the cardi- mainly glycolytic enzymes. exercise onset, next cascade-like FR and FI
ovascular system (carbon dioxide transport) and finally FF.
and via external respiration (gas exchange).
The physiological demands, i.e. maintenance
of a sufficient oxygenation of the tissue as
well as a physiologically tolerable pH value
in the blood serum are met by a precise hu-
moral and neuromechanical regulation me-
chanism. This sets the varying parameters (re-
spiration, circulation, metabolism) by
homeostasis as required at rest and during
exercise.
Cellular respiration and muscular
bioenergetics
Muscle contraction and its power are based
on the interaction of the contractile proteins
actin and myosin. This energy-consuming
process is made possible by hydrolytic sepa-
ration of phosphate from ATP molecules.

Fig. 2

14 VIASYS info Special Edition CPET, April 2002


The load-dependent recruitment of different
types of fibers and consequent different me-
tabolic pathways (type I fibers Î type IIb
fibers) are an explanation for the predomi-
nant aerobic processes during onset of in-
cremental exercise as compared to the pre-
dominant anaerobic processes (type IIb fi-
bers - FF fibers) at the end of exercise. The-
se mainly work glycolytically and under in-
creased lactate production, but each having
a higher contractility (FR Î FI Î FF fi-
bers).
At rest and with the onset of exercise, mus-
cular energy (ATP) is yielded from glucose
and fat under aerobic conditions. With
increasing work rate and on the basis of a
continuoulsy increasing O2 demand a relati-
ve O2-deficiency occurs in the tissue in ad-
dition to ATP regeneration giving rise to an
increase in anaerobic processes (involving
the already mentioned fiber types FR, FI, FF),
which form less ATP, but more lactate and
H+ions as well as CO2.
Under the anaerobic conditions of muscular
metabolism, CO2 forming is four times higher
giving rise to an increasing acidosis. Simul-
taneously, increasing lactate production du-
ring anaerobic glycolysis and increasing tis-
sue acidosis result in an unproportional rise
in ventilation or ventilatory demand (anae-
robic threshold) during exercise (Fig. 1, 2,
3).
With steadily increasing exercise, muscle fi-
bers are increasingly recruited and blood sup-
ply and consequently O2 supply to the mus-
cles continuously increase. Simultaneously,
CO2 production in the muscles rises as a li-
near function.
VIASYS info Special Edition CPET, April 2002
At a load range, which physiologically is
between 40% and 65% of the individually
achievable maximal O2 uptake (VíO2 max.),
Fig. 3
CO2 production has a greater slope than O2-
consumption as aerobic processes of energy
production are increased due to recruitment
of IIa and IIb fibers. Consequently, the pro-
duction of lactate and H-ions rises and CO2
even rises by four times the normal amount.
In order to counteract the resulting tissue aci-
dosis, ventilation is stimulated unproportio-
nally to the previously increased O2 demand
via chemoreceptors. During exercise, this
gives rise to an unproportional increase of
ventilation (VíE/VíO2) in the presence of
an increasing respiratory exchange rate (RER
= VíCO2/VíO2).
This ventilatory adjustment to anaerobic
metabolic conditions, i.e. the unproportional
rise of the ventilatory equivalent for oxygen
(VíE/VíO2) under exercise is termed as "an-
aerobic threshold" (ATan). The simultaneous
unproportionate CO2 production and release
(VíCO2) can be illustrated by the steeper slo-
pe of the VíCO2 curve as compared to the
VíO2 curve under increasing load. In this
way, the anaerobic threshold (ATan) can be
constructed geometrically from the curve
trends of VíO2 and VíCO2. This threshold is
at 40 - 60% of VíO2 max. Consequently,
RER, which under exercise decreased to va-
lues < 0.8, will again increase.
When exercise is continued, H-ions are in-
creasingly produced beyond aerobic thresh-
old, which give rise to a further central sti-
mulation of ventilation exceeding the alrea-
dy high VíCO2-dependent increase. Here, at
approximately 70 - 90% of VíO2 max, the
slope of the VíE-curve, which followed the
Practical Guideline
course of the VíCO2 and VíO2 slope until
AT was reached and beyond AT followed the
course of the VíCO2 curve, changes again
and may show a steeper slope than VíCO2.
This is called the "Respiratory Compensation
Point" and shows that tissue acidosis is in-
creasing (as a result of muscle fatigue). The
anaerobic threshold and the "Respiratory
Compensation Point" can also be calculated
on the basis of the respiratory equivalents
of O2 (EQO2 = VíE/VíO2) and CO2 (EQCO2
= VíE/VíCO2). Please refer to Fig. 4.
A permanent increase of EQO2 during exer-
cise reflects the anaerobic threshold, whe-
reas the rise in EQCO2 beyond AT reflects
the "Respiratory Compensation Point" (Fig.
4).
The neural and humoral regulation mecha-
nisms, which influence the ventilatory adjust-
ment to ventilation, are very complex and yet
not completely known. They cannot be
discussed in the frame of this essay (also com-
pare 25).
Respiratory mechanics during exercise
Effective ventilation (VíE in l/min) is deter-
mined by tidal breathing (VT in ml) and brea-
thing frequency (BF in breaths/min). During
exercise both parameters will increase in
healthy subjects. At a low work rate, VT ri-
ses first (up to approximately 50% of VC).
Next, VT and BF will increase similarly. At
approximately 70 - 80% of VíO2 max BF can
generally only be increased.
The dominant increase of VT during the on-
set of exercise is a result of a continuous de-
cline in the endexpiratory reserve volume and
an increase in the endinspiratory pulmonary
volume. Especially the endexpiratory decline
in pulmonary volume during exercise opti-
mizes the power/length ratio of the respira-
tory muscles (26).
At higher work rates, the increase in brea-
thing frequency is characterized by a declined
expiration time (t E) and an increased inspi-
ration time (t I), i.e. ( ti / t TOT > 0.4 - 0.55)
(25). The breathing frequencies achieved du-
ring exercise are between 50 - 60/min (23).
In healthy subjects, the airway resistance
changes during exercise as a result of bron-
chodilation, which can be due to a decline in
vagal stimulation (27), an increase in sym-
pathic afference or a release of NO (28).
Despite bronchodilation, the increase in VT
during exercise gives rise to an increase in
respiratory work as elastic respiratory work
increases (thoracic expansion, expansion of
the lung tissue). Additional factors for an in-
crease in resistance at rising VT are the in-
creasing flow turbulances as well as dyna-
mic airway compression, which also occurs
in healthy subjects.
15
Practical Guideline
An increased ventilation during exercise
gives rise to an increased O2 demand of the
respiratory muscles (VíO2 resp.). At rest and
with moderate work rate, the share of VíO2
resp. of total VíO2 is reported to be approxi-
mately 5% (29, 30). In healthy athletes, this
share can increase to 7% up to a maximum
of 15 - 20% of VíO2.
Breathing reserve (BR) is defined to be the
difference between maximum voluntary ven-
tilation (MVV) and maximum ventilation
during exercise (VíE max):
BR = MVV - VíEmax.
Healthy subjects terminate the test with a
peak ventilation not exceeding 50 - 70% of
MVV. This is due to the fact that VT normal-
ly reaches only approximately 50 - 60% of
VC during exercise (31). Similarily, the ma-
ximum breathing frequencies achievable at
rest cannot be reached during exercise. Con-
sequently, these persons have a breathing re-
serve. However, top athletes utilize their
breathing frequency up to their breathing me-
chanism limit.
Gas exchange
Alveolar ventilation (VíA) and perialveolar-
acinic perfusion (Q) are the determinants of
gas exchange.
The balance between VíA and Q (VíA/Q)
defines the effectivity of gas exchange of a
certain alveolar region in the lung. Under cer-
tain conditions (physiological rest) there are
regions of different VíA/Q sections, e.g. in
dependant parts of the lung, perfusion is
higher than ventilation. Consequently, alve-
olar O2 pressure (PAO2) is lower and CO2
pressure (PACO2) is higher than in regions
of lower perfusion as compared to ventilati-
on.
16
During expiration the mixed expiratory CO2
pressure (PECO2) and the endexpiratory CO2
pressure (PET-CO2) can be measured.
Analogous measurements are responsible for
the expiratory/inspiratory O2.
The PECO2 is defined by a gas mixture,
which is determined by dead space (anato-
mical and physiological dead space) and al-
veolar ventilation. The parts of the lung with
different VíA/Q relation are responsible for
the composition of the gas mixture.
Therefore, the relation between arterial blood
gases and composition of mixed expiratory
gas concentrations are an index for the ef-
fectivity of gas exchange.
Physiological dead space (VD/VT) is calcu-
lated as follows:
VD/VT = (PaCO2 - PECO2)/PaCO2
As physiological dead space is an important
variable for gas exchange, a change in its
share can considerably contribute to the ad-
justment to the higher ventilatory demand
during exercise.
Fig.4
At rest, dead space ventilation (VD/VT) is >
30% and considerably declines in healthy
subjects (far below 20%). If, during dead
space ventilation measurement, PETCO2 is
measured instead of PaCO2, dead space ven-
tilation is overestimated in normal subjects
and underestimated in patients with lung di-
sease. That's why many evaluation programs
allow the entry of the arterial PaCO2 as a cor-
rection factor for dead space calculation.
Oxygen saturation which during exercise is
mainly measured as PaO2, is kept in the range
of the values measured at rest in healthy sub-
jects.
It should, however, be noted that with capil-
lary PaO2 measurement, the arterial PaO2 val-
ues are not always correct (32). Additional-
ly, it should be pointed out that the precision
of blood gas analyzers can vary (33), so that
only changes of values > 5 mmHg should be
considered. Yet, despite these technical
measurement problems, certain deviations
from the initial PaO2 under load (up to < 70
mmHg) are experienced while testing healthy
patients (older patients, competitive athletes)
under physiological conditions.
Both alveolar and arterial O2 pressures will
discretely change during exercise (Fig. 5).
Furthermore, alveolar-arterial pressure dif-
ference rises. At rest, the value is approxi-
mately 8 mmHg (30) and can amount up to
40 mmHg in top athletes (31). The cause for
the increase of this difference is thought to
be a limitation of O2 diffusion and an incre-
ase in V'A/Q mismatch (31).
Cardiovascular response
Systemic oxygen transportation to the work-
ing muscles depends on the blood supply of
the tissue (Cardiac Output) and on the oxy-
gen contents of the arterial blood (= arterial
O2 pressure + contents of hemoglobin + O2
to hemoglobin affinity). The increased oxy-
gen transportation during exercise is prima-
rily achieved by increasing cardiac output.
With increasing work rate, oxygen uptake
and cardiac output will increase in a linear
relation (Fig. 6).
These parameters rise until an individual
maximum value is reached. This point is re-
ferred to as maximum oxygen uptake (VíO2
max) and forms an individual plateau value
that cannot be exceeded. Consequently, VíO2
max is a stable and reproducible individual
physiologic variable in humans. Age and
body position (lying, upright position) will
change the increase in cardiac output in rela-
tion to exercise (slope and absolute values)
due to the different cardiac pumping behavi-
or.
Cardiac output can be increased dependent
of work rate by increasing both heart rate
and stroke volume. Depending on the indivi-
dual training condition, the stroke volume in
well-trained subjects is first increased from
approx. 60 to 200 ml (30), followed by an
increase in heart rate. On the contrary, in un-
trained subjects cardiac output is increased
via an increase in heart rate. The poorer the
subject's training condition is, the faster heart
rate increases. On the other hand, a person's
physical training will increase stroke volu-
me and reduce heart frequency (Fig. 6)
VIASYS info Special Edition CPET, April 2002
 Practical Guideline

Exercise Protocols
Treadmill

Bruce Protocol 4 steps /3 minutes

(1.7 mph and 10% slope up to 4.2 mph and 16 % slope)

Balke Protocol Constant speed and increase of slope by 1%/min.

Naughton 15 test steps of 3 minutes each, starting at 3.2, km/h with 3.5% slope/3 min.
respectively and increase in speed by 1.6 km/h every 6 min.
Bicycle ergometer

Incremental exercise test 60 RPM; increase 5 - 25 W/min.; planned test duration 6-12 min
Test termination: exhaustion or termination criteria

Ramp Continuously increasing exercise; increase at a one-second interval

Stress testing methods

An acute increase of haematocrit with heavy
work load is possible in healthy subjects;
however, this is not an important factor re-
garding improvement of oxygen transporta-
tion while exercising (30). In top athletes,
however, training gives rise to an increase in
blood volume and consequently in oxygen
transport capacity and thus becomes relevant
for an increase in exercise capacity.
Oxygen pulse (VíO2/HR) is a variable that
can be determined by cardiopulmonary exer-
cise testing and can be deduced from the pro-
duct of stroke volume and the difference of
arterial and central-venous oxygen contents
i.e. VíO2/HR = SV x (CaO2 - CvO2).
Fig. 5
Assuming that one of the variables (e.g. SV)
remains constant during exercise, oxygen
pulse is a function of the other respectively.
During exercise, arterial-venous O2 diffe-
rence remains constant as long as oxygen
utilization and consequently arterial-venous
O2 difference increases at the end of exer-
cise. From now on oxygen pulse can be re-
garded to be an indicator for the increase in
stroke volume.
Standardized str ess tests can be performed
stress
with the help of:
- bicycle ergometers
- treadmill ergometers
- hand-cranked ergometers
Each of these methods has certain benefits.
The decision as to which method is used de-
pends on the space available and on the
amount of patients to be tested. The test re-
sults and predicted values are to be stated
dependent on the applied testing method. It
should however, be noted that with treadmill
tests V'O2 max is about 7% - 10% higher than
with bicycle tests. Whereby ventilatory and
lactate parameters will be higher with bicyc-
le tests than with treadmill tests (34, 35, 36).
The test results are, furthermore, consider-
ably influenced by the selected load proto-
col. Basically, we can differentiate between
constant and constantly-increasing work load
types.
Dif fer
Differ ent modalities of constant exer
ferent cise
exercise
tests have been developed:
- Maximum work load for a constant time.
- Constant work load with a duration of
6 min.
- Intermittent constant work load with a du-
ration of 6 min. with an increase in work
load between two tests, whereby the pause
between the tests is between 15 min. and
24 hours.
Constantly increasing work loads can be real-
ized in one test aiming at stressing the patient
to a maximum.

VIASYS info Special Edition CPET, April 2002 17

Practical Guideline
Normal Athlete
Today, constantly increasing exercise tests
(maximum or submaximum stress) are main-
ly performed for practical reasons. The pre-
viously described constant exercise tests have
mainly been developed on the basis of sci-
entific approaches, such as the determinati-
on of VíO2 max or ventilatory kinetics. It
should, however, be pointed out that V'O2
max can only be precisely determined on the
basis of an intermittent constant exercise test.
With constantly increasing exercise, on the
other hand, that means without steady state
conditions, it is possible to achieve a peak
work load allowing to measure "VíO2 peak".
It is an individual peak value that is recor-
ded with the latter method, but not a plateau
value as demanded for VíO2 max (37).
It should be noted that the applied predicted
values have to be obtained with the same test-
ing method as applied during recording.
In Western Europe bicycle ergometry is main-
ly used. Work load steps of three or more
minutes steady state, that have been used a
few years ago, are not required. Steady state
cannot be achieved with maximum work load
(38).
18
Fig. 6
Today, mainly steps of 2 (-1) minutes are pos-
sible for technological reasons, however,
with simultaneous right-ventricular cathete-
rization different steps are required. The total
duration of work load should be approx. 10
minutes and should not exceed 15 minutes.
A duration of < 7 minutes can lead to errone-
ous results (39). Depending on the subject's
or patient's condition, the examination should
be planned in a way that the subject/patient
is stressed to a maximum, provided that no
submaximal exercise (50 - 85% of pred) is
to be achieved for clinical reasons.
Goals
The predicted exercise capacity can be esti-
mated as follows (38):
Watts pred = Body weight (kg) x 3(Male)
pred
Body weight(kg) x 2,5(Female),
minus 10% per age decade > 30 years, re-
spectively (38).
During bicycle ergometry 60 (70) RPM
should be used.
The slope of the exercise increase depends
on the planned exercise duration. However,
the absolute increase/min. between 20 and
50 watts will not influence the results during
ramp testing with healthy subjects (40,41).
In conclusion, we can say that symptom-li-
mited exercise tests should meet the follow-
ing demands: planned test period of 10 mi-
nutes, predicted work load according to cal-
culation given above, slope increase of work
load/minute according to these two parame-
ters. The initial work load should depend on
the estimated individual fitness.
Measurements should be taken at rest for a
period of at least 5 minutes before and after
the exercise (36).
Fig. 7
VIASYS info Special Edition CPET, April 2002
 Practical Guideline

Literature:
1. Goldhammer
Goldhammer,, S., Scherf, D.: Elektrokardiographische Untersuchungen bei Kranken mit Angina pectoris. Z.klin. Med. 122 (1932), 134 f.
2. Dietrich, S., Schwiegk, H.: Angina pectoris und Anoxie des Herzmuskels, Z. klin. Med. 125(1933),
195 f.
3. Hill, A.V., Long, C.N.H., Lupton, H. : Muscular exercise, lactic acid and supply und utilisation of oxygen. 1. Proc. Roy. Soc. London, Ser. B. 96 ( 1924), 438 - 475.
A.V.,
4. Scholander
Scholander,, K.F
K.F.., Analyser for accurate estimating of respiratory gases in one-half cubic centimeter samples. J. Biol. Chem. 167 ( 1947), 235 - 259).
5. Huckabee,W .E.
Huckabee,W.E.
.E., J. Clin. Invest., 37 (1958), 1577 - 1592, 1593 - 1602: The role of anaerobic metabolism in the performance of mild muscular work. I. relationship to
oxygen consumption and cardiac output, and the effect of congestive heart failure. II. the effect of asymptomatic heart disease.
6. Taylor
aylor,, H.L., Buskirk, E., Henschel, A. , J. appl. Physiol. 8 (1955), 73 ff: Maximal oxygen intake as an objective measure of cardio-respiratory performance.
7. Issekutz, B., Rohdahl, K.
K., J.appl. Physiol., 16 (1961), 606 - 610: Respiratory quotient during exercise.
8. Wasserman, K., Whipp, B.J., Koyal, S.N., Beaver
Beaver,, W.L.
.L., J. appl. Physiol, 35 (1973), 236 - 243 : Anaerobic threshold and respiratory gas exchange during exercise.
9 H.L. Taylor
aylor,, E. Buskirk, A. Henschel J. Appl. Phys. 8, (1955), 73 - 80: Maximal oxygen intake as an objective measure of cardio-respiratory performance.
10. Mellerowicz,H
Mellerowicz,H
owicz,H.Urban u. Schwarzenberg, M¸nchen, 1979: Ergometrie.
11. Gibbons, R. et al.
al., JACC 30 ( 1997), 260 - 315: ACC/AHA Guidelines for exercise testing. A report of the american college of cardiology/american heart association
task force on practice guidelines (committee on exercise testing).
12. Wasserman, K., Hansen, JE., Sue, DY., Whipp, BJ.
DY., BJ.: Principles of exercise testing and interpretation. Philadelphia: Lea and Febiger, 1987.
13. Eschenbacher
Eschenbacher,, W., Mannina, A.
A., Chest 97 (1990), 263 - 267: An algorithm for the interpretation of cardiopulmonary exercise tests.
14. Mc Connel, TR., Laubach CA., Clark BA., J Cardiopulmon Rehabil, 15 (1995), 257 - 261: Value of gas exchange analysis in heart disease.
15. Mitlehner ,W
Mitlehner,W ., Kerb,W
,W., Kerb,W. Respiration, 61 (1994), 255 - 266: Exercise hypoxemia and the effects of increased inspiratory oxygen concentration in severe chronic obstruc-
tive pulmonary disease.
16. Harris-Eze, AO., et al
al. Am. J Respir. Crit Care Med. 150 (1994), 1616 - 1622: Oxygen improves maximal exercise performance in interstitial lung disease.
17. Howard, DK., Iademar co EJ., Trulock E.P
Iademarco E.P,, Clinics in chest medicine 15 (1994), 405 - 420: The role of cardiopulmonary exercise testing in lung and heart - lung
transplantation.
18. Larsen,R., Svendsen, UG., Milman, N., Brenoe, J., Petersen, B.N.
Brenoe, B.N.; Eur. Resp. J.,10 (1997), 1559-1565: Exercise testing in the preoperative evaluation of patients with
bronchogenic carcinoma.
19. Bolliger
Bolliger,, CT et al
al., Am J Respir Crit Care Med 151 (1995), 1472 - 1480: Exercise capacity as a predictor of postoperative complications in lung resection candidates.
20. Mahler
Mahler,, DA., Horowitz, MB.
Horowitz, MB., Clinics in chest medicine 15 (1994), 259 - 270: Clinical evaluation of exertional dyspnea.
21. Marx, H.H., Klepzig, H.
Marx, H.: Medizinische Begutachtung innerer Krankheiten. Thieme Verlag, Stuttgart, 7∞, 1997.
22. American thorax society: Evaluation of impairment/disability secondary to respiratory disorders. Am Rev Respir. Dis, 133 (1986), 1205 ff.
23. Jones, N.L.
N.L.: Clinical exercise testing. W.B. Saunders, 3∞, 1988.
24. Whipp, B.J., Clinics in chest medicine, 15 (1994), 173 - 192: The bioenergetic and gas exchange basis of exercise testing..
25. Johnson, B D., Beck, K C
C., Allergic and respiratory disease in sports medicine, 11 (1997), 1 - 34: Respiratory system responses to dynamic exercise.
26. Dempsey
Dempsey,, JA, Hanson PG, Henderson, , KS, Schweiz. Z. Sportmedizin (1992), 40, 55 - 64: Demand vs. capacity in healthy pulmonary system.
27. Warren JG, Jennings SJ, Clark TJH
arren TJH, Clin. Sci. (1984), 66, 79 - 85: Effect of adrenergic and vagal blockade on the normal human airway response to exercise.
28. Morrison KJ, Gao Y, Vanhoutte PM
PM. Am J Phys.(1990), 258, L 254 - L 262: Epithelial modulation of airway smooth muscle.
29. Aaron EA, Johnson BD, Seow CK, Dempsey JA
Aaron JA, J Appl Physiol. (1992), 72, 1810 - 1817: Oxygen cost of exercise hyperpnea: measurement.
30. Murray J F: The normal lung.2∞, W.B. Saunders, 1986.
31. Whipp, BJ, Wagner PD, Agusti A: in European respiratory monograph (1997), 2,6, 3-31: Response to exercise in healthy subjects.
32. Sauty
Sauty,, A, Uldr
Uldryy, C, Debetaz L-F
L-F,, Leuenberger
Leuenberger,, P
P,, Fitting, J-W
J-W,, Eur. Respir. J. (1996), 9, 186 - 189: Differences in PO2 and PCO2 between arterial and arterialized
earlobe samples.
33. Scuderi, Ph E, Macgr egor
egor,, DA, Bowton, DL, Harris, LC, Anderson, R, James, RL
Macgregor RL, Am Rev. Resp. Dis. (1993), 147, 1354 - 1359: Performance characteristics and
interanalyser variability of PO2 measurements using tonometered human blood.
34. Shepard, RJ, Int Z. angew. Physiol. (1966), 23, 219 - 230: The relative merits of the step test, bicycle ergometer and treadmill in the assesment of cardio-respiratory
fitness.
35. Shepard, RJ
RJ, Standard tests of aerobic power. In Shepard RJ, : Frontiers of fitness, Charles E. Thomas, Springfield, 1971.
36. Hansen, JE, Am Rev Resp. Dis. (1984), 129 Suppl. S 25 - S27: Exercise instruments, schemes and protocols for evaluating the dyspneic patient.
aylor,, HL, Buskirk E., Henschel A, J appl. Physiol. (1955), 8, 73 - 80: Maximal oxygen uptake as an objective measure of cardio-respiratory performance.
37. Taylor
38. H. Lˆllgen. Kardiopulmonale Funktionsdiagnostik, Editio CIBA , Ciba - Geigy, Wehr, 2∞, 1992.
39. Buchf¸hr
Buchf¸hrer er MJ, Hansen JE, Robinson TE, Sue DY
DY,, Wasserman K, Whipp BJ
BJ: Am Rev Respir Dis (1982), 125, Suppl., 259: Optimizing the work rate protocol for
clinical exercise tests.
40. Whipp BJ, Davies JA, Torres F
orres F,, Wasserman , J Appl Physiol (1981), 50, 217 - 221: A test to determine parameters of aerobic function during exercise.
41. Davies JA, Whipp BJ, Lamarra N, Huntsman DJ, Frank MH, Wasserman K, Med Sci Sports (1982), 14, 339 - 343: Effect of ramp slope on measurement of aerobic
parameters from the ramp exercise test.
42. H. Roskamm, H. Reindell
Reindell: Herzkrankheiten, Springer Verlag, Berlin. 1982.

Wolfgang Mitlehner, M.D.

Internist
Pulmonary and Bronchial Diseases, Allergology
Specializing in Pulmonology and Oncology
Turmstr. 21, Haus K
D-10559 Berlin

+49 (0)30 3918747
 +49 (0)30 39903889
eMail: wolfgang-mitlehner@t-online.de
www.dr-mitlehner.de

VIASYS info Special Edition CPET, April 2002 19

Diagnostics
Vmax and Cardiosoft
CPET by SensorMedics,
ECG by Marquette Hellige.
Are you looking for a sophisticated, high-end
cardiopulmonary exercise testing system and
don't want to go without a high-quality ECG
system? SensorMedics provides a perfect
solution and combines two leading products
in one system.
Thanks to the close cooperation with Mar-
quette-Hellige, SensorMedics successfully
combined Vmax and Cardiosoft in one sys-
tem. Five different screen displays, that can
be selected during the test allow you to decide
whether you want to view CPET or ECG data
only or whether you want to combine all data
on one screen.
Of course, patient data doesn't have to be en-
tered twice; a special program does that for
you automatically. It is also possible to re-
cord an individual stress ECG or, optionally,
an individual ECG at rest.
Above:
CPET including Vmax
Right:
Vmax CPET including Hellige ECG
20
SensorMedics Vmax product series
Vmax is a versatile cardiopulmonary exer-
cise testing system which meets the demands
of doctors whether they be in hospital or pri-
vate practice. Whether you need a system for
routine testing or research, for adults or child-
ren, for patients or athletes - Vmax can al-
ways be tailored to your needs. Vmax is an
open system that allows you to record im-
portant parameters such as O2 uptake, CO2
output, RER, ventilation (V'E), O2 pulse etc.
on a breath by breath basis. The results can
be displayed on-line in numeric and graphic
form. The test can be performed via mouth-
piece or mask.
The lightweight mass flow sensor is insen-
sitve to moisture and always provides high-
ly-precise ventilatory data due to its small
dead space.
With Vmax, you define the product. You
might even design your own configuration,
for example with indirect calorimetry, diffu-
sion measurements (even during exercise),
cardiac output, P0.1, bodyplethysmography
etc.
Vmax, of course, provides a program for pul-
monary function analysis. You can easily
measure the flow-volume loop at rest and
during exercise and display both loops in one
screen for diagnosis of a ventilatory impair-
ment.
All data at a glance:
Stress ECG with CPET results
VIASYS info Special Edition CPET, April 2002

Spirometry/Flow-Volume
Last but not least, Vmax makes it possible to
perform a bronchial challenge testing with
the flow-volume loop.
SensorMedics has always attached great im-
portance to absolute precision. The analyzers
can be checked during automatic 2-point ca-
libration. The same applies to volume calib-
ration. A further unique feature is the built-
in quality control for correct measurement
performance. If required, the system indica-
tes accuracy and reproducibility of the flow-
volume loop.
The fast and precise analyzers meet the high-
est standards and, unlike other types of ana-
lyzers, don't have to be exchanged at regular
intervals.
The help program is a real trendsetter that
explains and illustrates every measurement
and setting with the assistance of animated
pictures. The tutor on CD-ROM, which is
included, provides valuable information
regarding measurement technology and pa-
rameters.
Above
F/V loop during exercise
Left:
Spirometry measurement
VIASYS info Special Edition CPET, April 2002
Diagnostics
Cardiopulmonary Exercise Testing Indirect Calorimetry
Marquette-Hellige*1-ECG
The Hellige ECG is a first-class 12-channel The advantages at a glance:
PC-ECG and consists of Corina amplifier and
Powerful analyzers
Cardiosoft software. Thanks to clinical veri-
fication, the algorithms for ECG analysis of Flow-volume loop during exercise
Marquette-Hellige are the most precise and Report Maker
reliable algorithms in the world. You can Predicted Value Maker
either use adhesive electrodes or the KISS
Tutor
suction electrodes. During stress ECG recor-
ding, a real-time arrythmia analysis and a 12- Arrhythmia detection
channel on-line ST analysis is performed. CPET stand-alone
The Hellige Cardiosoft program automatical-
ly controls the ergometer, as well as the blood
pressure measurement so that you can con- Items included:
centrate on your patient.
Optionally, the 12-channel ECG can be con- Computer, color ink-jet printer and
tinuously saved. ECG at rest including di- monitor on an ergonomic trolley
mensioning and interpretation is also avail- Vmax analyzer and test module
able as an option. Vmax software "Vision"
Comprehensive help program Vmax
"Tutor"
Amplifier "Corina" made by
Marquette-Hellige
Software "Cardiosoft" made by
Marquette-Hellige
KISS suction electrodes or leads for
adhesive electrodes
Integrated isolating transformer
Calibration pump
Accessories kit
*1
a GE Medical Systems company
Vmax CPET and
Hellige ECG
21
Diagnostics

All features at a glance:

Vmax Hellige-ECG Cardiosoft

Maintenance-free O2/CO2 analyzer z Amplifier module "Corina" z
Ambient module for temperature and pressure z Software "Cardiosoft" z
Mass flow sensor z Adhesive electrodes or KISS suction unit z
Breath by breath z
Interface to SensorMedics Vmax z
Mixing chamber {
Powerful PC z Data base z
Color ink-jet printer z 12-channel ergometry program z
Mobile cart z On-line arrhythmia detection z
Volume calibration program z Warning in case of critical arrhythmias z
Automatic gas calibration z On-line-ST analysis z
Patient data base z Trend graphs z
Spirometry/flow volume program z Single electrode control z
CPET program z HR alarm, acoustically and optically z
Entry of blood gas analysis values including markers z Anti-drift system z
Capnogram display z 35 Hz and 50 Hz filter z
Off-line entry of blood pressure, SaO2 z Automatic zeroing z
User-specific graphics design z Display as on recording paper z
User-specific parameter tables z Exercise control z
Flow-volume loop during exercise z On-line storage of entire ECG {
Automatic AT calculation z ECG at rest {
Manual AT calculation z Interpretation of ECG at rest {
Automatic VO2 peak calculation z Arrhythmia marking and classification {
Manual VO2 peak calculation z
Warning if limit value is exceeded z
Screen and printer reports z z Standard { Option
User-specific design of assessments z
Predicted value editor z
Work load control z
Measurement with elevated/lowered FIO2 {
Indirect calorimetry z
- with hood {
- for ventilated patients {
- hood with elevated FiO2 {
- hood for children {
Cardiac output {
Single breath diffusion measurement {
Intrabreath diffusion measurement {
Diffusion during exercise {
Membrane measurement {
FRC measurement N2 washout {
O2 single breath for closing volume {
Bodyplethysmography {
P0.1/Pmax {
Compliance {
Provocation {
Pulse oximeter { Cardiopulmonary exercise testing
Calibration and test gas {
Pressure reducer { and ECG
Network {
Lung function interpretation program { perfectly combined
3-channel ECG z
in one unit.
z Standard { Option

22 VIASYS info Special Edition CPET, April 2002

 Diagnostics

Oxycon Mobile
A milestone in CPET
Execellent diagnostic possibilities are achieved
by traditional stress testing equipment like
treadmill and bicycle ergometer.
Up until now this equipment has been limited to
indoor usage.
Now we have the Oxycon Mobile.

Oxycon Mobile offers on-the-spot measure-

ments of all relevant CPET parameters. The
small sophisticated unit is attached to a
comfortable belt system. This is slipped over
the test subject's shoulder. The test can be
performed via a breathing mask and the
subject is not impeded by tubes and cables.
The recorded data is telemetrically transferred Main features:
to the PC or saved on a small chip card. After
being transferred, the data is analyzed using
the powerful Oxycon Software by Jaeger.
Oxycon Mobile records all key parameters
such as:
Ventilation V'E
VO2, VCO2
Anaerobic threshold
RER
HR
EQO2, EQCO2
Telemetric data transfer
Portable, lightweight unit attached to
a belt system, which is slipped over
the shoulders.
Complete CPET test including flow-
volume loop, heart rate, ECG,
anaerobic threshold etc.
Long-range telemetry for real-time
data monitoring
Applicable to a wide range of test
subjects from seriously ill patients to
elite athletes
Powerful evaluation software with
report generator
Fields of application:
Pulmonology, cardiology, intensive care
Suspected stress-induced asthma
Monitoring of patients with heart
diseases
Monitoring of parenteral fed patients
Rehabilitation
Therapy monitoring
Occupational medicine
Determination of occupational
exercise tolerance
Determination of degree of handicap
Sports medicine
Optimizing of training

Fig. left:
Display of anaerobic
Belt system threshold

VIASYS info Special Edition CPET, April 2002 23

Essay

Clinical Importance of CPET

Author: Prof. Karl-Heinz R¸hle, M.D.

In regards to exercise tolerance, cardiopulmonary exercise testing is an excellent tool for diagnosis and
therapy. However, the values obtained at rest during cardiopulmonary function diagnostics are often not
enough to establish a proper therapy. The results of cardiopulmonary exercise testing can be interpreted on
the basis of the nine-panel graph which gives a clearly structured overview of exercise capacity, cardiac
parameters, pulmonary performance values and gas exchange parameters.

Indications for cardiopulmonar

cardiopulmonaryy exercise testing
exercise
A. Disability assessment
Maximum exercise capacity
Factors of exercise limitation

B. Risk/pr ognosis
Risk/prognosis
Risk assessment prior to pulmonary resection (pneumonectomy, lobectomy)
Risk assessment prior to heart transplantation

C. Therapy assessment
Training
O2 therapy
Drug therapy

A. Disability assessment
Maximum exercise capacity
With good patient effort, definition of maxi-
mum oxygen uptake is the best method to
define a subject's physical exercise capacity.
Indication that the subject has reached his/
her maximum exercise capacity is the pla-
teau-formation of the continuously measured
V'O2 in the ramp protocol, despite increasing
work load. This value is referred to as V'O2
max. If V'O2 rises only slightly, one can be
sure that the patient is stressed to a maxi-
mum and consequently a cardiopulmonary
limitation is present. This is of special im-
portance for disability assessments. If no pla-
teau is reached, we talk about Peak V'O2 (or
V'O2 peak). In fact, this is the highest V'O2
achieved during the test. Here, it is not pos-
sible to decide whether patient effort was
good or not.
In this context, it is helpful to consider base
excess (BE). If this value falls below -6 up
to -9 mmol/l in healthy subjects, it can be
assumed that the subject has been stressed to
a maximum.
Especially in the presence of pulmonary di-
seases maximum exercise capacity cannot be
exactly predicted on the basis of functional
parameters measured at rest.
It is therefore indispensable for disability
assessments to describe the impairment
caused by e.g. functional pulmonary or car-
diac disorders during exercise, as well as the
resulting reduced exercise capacity on the
basis of V'O2 max. Functional impairments
are highly relevant with regard to their ef-
fects on occupation and way of life.
Disability
In some occupations, people are exposed to
short-termed maximum loads. By determin-
ing V'O2 peak, it can be decided whether the
subject can meet this requirement during spe-
cific conditions (disability for a certain oc-
cupation).
The measurement of V'O2 peak provides im-
portant information about the endurance ca-
pacity. The demands of a normal 8-hour
working day should be considerably below
the endurance limit.
If an exact description of the working place
including the average oxygen uptake during
work or power in watts is available, disabili-
ty can be better assessed by determining
maximum oxygen uptake with regard to the
possible performance.
Factors of exercise limitation
Even with a great deal of expenditure cardi-
opulmonary exercise testing only allows to
describe approximately 50% of the influenc-
ing factors. Other limiting factors, such as
dyspnea or claudicating pain cannot be quan-
tified objectively. A study with COPD pa-
tients showed that in 46% of all cases musc-
le exhaustion was the main cause for exer-
cise cessation. Cessation due to dyspnea was
only reported in 36 % of the cases. Patients
with interstitial pulmonary fibrosis however
ceased exercising due to dyspnea (62%) and
muscle exhaustion (25%).
To determine maximum oxygen uptake, the
Borg scale is highly recommended. Dyspnea
often rises linearly with increasing work load
(V'O2,Watt or V'E/MVV); however, the work
load dependant increase of dyspnea varies
with the type of disease and can also be used
to estimate the probable maximum exercise
capacity during examination.
An important aspect of cardiopulmonary
exercise testing is that it allows to exclude a
relevant cardiopulmonary impairment.

24 VIASYS info Special Edition CPET, April 2002


This is valid, whenever a patient complains
about stress dyspnea, but nevertheless rea-
ches his/her steady state/unsteady state exer-
cise capacity according to the respective re-
ference values. Consequently, exercise capa-
city is normal but the subjects are either not
able to assess their condition or suffer from
psychogenically induced dyspnea. With nor-
mal exercise capacity the patient can be re-
assured. Alternatively a psychotherapy or a
drug therapy (sedatives, anxiolytics) can be
prescribed. Additional examinations are
often not required. Lack of training and
reduced exercise capacity, for example in
case of adipositas, cannot be differentiated
from cardiac impairments.
It should be generally noted that the results
of the cardiopulmonary exercise test cannot
be assigned to a specific clinical picture, but
only provides important information for fur-
ther diagnosis. Poorly trained subjects or pa-
tients with cardiac diseases have a similiar
reduced maximal oxygen uptake, breathing
reserve (MVV/V'E), oxygen pulse and low
anaerobic threshold. Reduced load capacity,
including the early onset of lactic acidosis,
indicate a poor training condition. This in-
formation cannot be obtained by clinical data,
body-plethysmography or blood gas analy-
sis at rest.
B. Risk/pr ognosis
Risk/prognosis
Risk assessment prior to pulmonary
resection
By quantifying the functional reserves, in the
case of pulmonary resection it is possible to
define which patients are at risk and conse-
quently the pre/post-surgical mortality rate
declines. An important goal is the pre-surgi-
cal determination of the risk for
complications after a major surgery. Nowa-
days the most important information is re-
trieved out of the measured static and dyna-
mic lung-volume before surgery, out of which
the post-surgery values for FEV1 can be de-
rived and estimated, even better in combina-
tion with a quantitative perfusion-scintigra-
phy. Due to the high discrimination, deter-
mination of maximum V'O2 for estimation
of the surgical risk is favored.
+49 (0)2331 974 0
VIASYS info Special Edition CPET, April 2002
If V'O2max is less than 60% of the predicted
value, the removal of more than one lung lobe
is not recommended.
If V'O2max is higher than 75% of the predic-
ted value it can be assumed that no post-sur-
gical complications will occur.
Risk assessment for heart transplant
patients
Prognosis and clinical trend in the case of
cardiac insufficiency can be examined on the
basis of the patient's own account, according
to NYHA classification or by objective test-
ing procedures with the help of Wmax or
V'O 2 peak. There is a good correlation
between the measured V'O2 peak and the
mortality in patients with heart failure accor-
ding to NYHA III and IV.
With a cutoff of V'O2max below 10 ml/kg/
min. mortality after one year is 77%.
C. Therapy assessment
Training
One of the most important tasks of rehabili-
tation is the increase of exercise capacity by
training the muscles of the upper and lower
extremities.
In the case of COPD, maximum exercise ca-
pacity is limited during exercise as the large
and small airways will collapse. As the end-
expiratory volume increases with increasing
work load, the lungs are working in an unfa-
vorable area of the pressure-volume-curve.
Furthermore, there is fatigue of the periphe-
ral muscles, increasing hypoxemia in the pre-
sence of severe obstruction, a reduction in
cardiovascular capacity as well as the incre-
ased lactic acidosis in the presence of a re-
duced capacity of the peripheral muscles.
In the case of COPD, cardiopulmonary exer-
cise testing is important to control muscle
training, i.e. when defining work load levels
for training purposes.
At the beginning of an exercise program the
exercise intensity, at which an increase in
exercise capacity under training is to be ex-
pected, has to be defined. However, there
are still no standardized guidelines regarding
duration, frequency and intensity of training.
Prof. Karl-Heinz R¸hle, M.D.
Klinik Ambrock
Ambrocker Weg 60
D-58091 Hagen
eMail: klinik-ambrock.pneumo@t-online.de
Essay
With the help of a ramp protocol, maximum
exercise capacity, as well as a range for trai-
ning can be defined on the basis of which
the anaerobic threshold is determined. Some
studies recommend a range from 50% of peak
oxygen uptake to values below maximum
oxygen uptake.
Cardiopulmonary exercise testing allows to
objectively quantify the success of training
programs. Parameters to be measured are,
among others, maximum oxygen uptake, lac-
tate, minute volume, breathing frequency,
V'CO 2 , ventilatory equivalents, heart
rate,VD/VT and anaerobic threshold. These
parameters can be determined best on the
basis of a ramp protocol performed prior to
and after training.
O2 therapy
To compensate hypoxemia and its effects on
exercise capacity, it can be attempted to in-
crease exercise capacity by O2 insufflation
during exercise. Studies regarding O2 thera-
py in the presence of different pulmonary di-
seases are available for patients with COPD,
interstitial fibrotic lung diseases and cystic
fibrosis.
Drug therapy
Endurance capacity is a very sensitive and
clinically relevant variable for evaluating
drug effects, especially of fl-sympathicomi-
metics and anticholinergics. By measuring
lung volumes such as FEV1, FVC and inspi-
ratory capacity (IC), an improvement after
administration of anticholinergics can be
documented. Hyperinflation at rest, measu-
red via IC, is a very good predictive parame-
ter of V'O2 max. Dynamic hyperinflation and
the simultaneous increase of the endexpira-
tory volume (EELV) during exercise and
their reduction after administration of
antiobstructive medication correlates best
with the increase in endurance capacity.
25
Essay

Evaluation and Interpretation

of a cardiopulmonary exercise test
Author: Hermann Eschenbacher, Ph.D.

Cardiopulmonary exercise testing is a comprehensive testing procedure suited for differential diagnosis and
examines a subject's cardiopulmonary exercise capacity or limitation. In addition to cardiac parameters,
(e.g. stress ECG) respiratory parameters are recorded at defined work rates. The test provides a variety of
parameters which, as compared to the individual stress ECG, allow for a comprehensive assessment.

The goal of this essay is to explain an easy
and understandable procedure that allows
assessment of individual areas of exercise li-
mitation in order to deduce clear results.
There are a variety of proposals and flow
charts in literature (e.g. Eschenbacher (1990),
Roca (1997), Wasserman (1999), Schardt
(1999)) describing certain methods, one of
which is the evaluation on the basis of the
nine-panel graph. This method has been re-
commended by Wasserman for years and has
been proven to be well suited. Although re-
cording of the dynamic flow-volume loop
during exercise, which has become increa-
singly important during the past years, has
not yet been considered. As seen in Fig. 1,
the nine-panel graph can be divided into se-
veral areas (whereby the graphs are numbe-
red from left to right):
Ventilation: Graph 1, 4 and 7
Cardiopulmonary: Graph 2, 3 and 5
Gas exchange: Graph 6, 9 and 4
Metabolism: Graph 8
Anaer obic thr
Anaerobic eshold: Graph 5, 6, 8 and 9
threshold:
Recording of the flow-volume loop during
exercise and comparing it with the maximal
flow-volume loop provides additional infor-
mation, mainly on ventilatory limitations
(Fig. 2).
Comments on the evaluation and interpreta-
tion of a cardiopulmonary exercise test with
the help of these graphs, explained step by
step, follow. As far as the sequence of the
individual graphs is concerned, there are dif-
ferent views (e.g. Wasserman (1999), R¸hle
(2001)) depending on where emphasis is
placed.
As far as I'm concerned, the procedure de-
scribed below is the best suited.
Assessment of cardiac (cardiopul-
monar y) exer
monary) cise capacity
exercise
What is the subject's exercise capacity
exercise
(Graph 3)?
On the basis of the predicted values in Graph
3, it can be immediately recognized whether
the subject has reached or even exceeded his/
her expected exercise capacity and oxygen
uptake (as in Fig. 1: 194% pred). If reached,
these values clearly show that none or at least
no severe limitation or impairment is pres-
ent. It should, however, be noted that oxy-
gen uptake in obese subjects is higher than
in persons of normal weight. This is due to
the increased body mass and means that oxy-
gen uptake, although reduced, can reach nor-
mal values if the overweight is not conside-
red in the predicted values (see Fig. 3 => se-
lect correct predicted values!).
How does oxygen uptake increase during
increase
exercise (Graph 3)?
exercise
Linearity?
In healthy subjects, oxygen uptake normally
increases linearily with increasing work load
and, according to Wasserman, can be
estimated as follows:
V'O2 [ml/min] = 151 mL/min + 5.8*body weight[kg]
+ 10.5 * work load[Watt]1
load[Watt]
This linear relation is also valid for obese
subjects (Fig. 3, left); however, oxygen
uptake is parallel shifted upwards due to body
weight.
Flatening with increasing work rate?
Each subject has an individual cardiovascu-
lar/cardiopulmonary limitation, which is re-
flected by a flatening in oxygen uptake de-
spite increasing work load. However in nor-
mal subjects, this flatening is often not rea-
ched (xV'O2 peak), as this requires a lot of
effort and healthy subjects are rarely willing
to do so, so that this flatening is only rea-
ched with really limited patients or with top
athletes who stress themselves to a maximum
(Fig. 3 - right).

1 2 3

4 5 6

7 8
9 Fig. 1 (left): CPET test on the basis of the nine-panel graph. The graphs are
numbered from left to right as follows: 1-3, 4-6 and 7-9.
Fig. 2. (top): Left curve: Maximal and dynamic F/V loop of a subject with no
limitation. Right curve: Obstruction. The graph shows that ventilatory limitation
is reached (flows, tidal volume).

26 VIASYS info Special Edition CPET, April 2002


As long as the individual body cells are suf-
ficiently supplied with oxygen, the increase
is linear. As soon as the supply is no longer
sufficient, the curve flattens. If limitation
starts already below the predicted value, we
can assume for sure that exercise capacity is
limited. Limitation is the greater, when flaten-
ing starts earlier. Nevertheless, the body has
to meet the increased demands, which means
that energy has to be produced anaerobical-
ly. Due to the limited anaerobic capacity, the
subject will soon stop exercising depending
on his/her individual reserves.
Slope of oxygen uptake?
Another important aspect is the increase of
oxygen uptake during exercise. The slope of
V'O2 with increasing work load (= aerobic
capacity, normally approx. 10.5 ml/watt1, see
above) provides information on whether the
peripheral muscle cells are sufficiently sup-
plied with oxygen. If not, for example in the
presence of peripheral stenosis or a left ven-
tricular functional impairment, a lower slo-
pe can be observed (Fig. 3, center). To be
able to assess this increase, it is recommen-
ded to simultaneously record work load in
Graph 3 and to plot it in relation to V'O2 with
a scale of 1:10 (an increase of 1 watt equals
an 10 mL V'O2 increase), so that both slopes
can be directly compared with each other (see
Fig. 1, Graph 3: green and blue curve).
Does heart rate rise continuously; what is
maximum HR (Graph 2)?
In healthy subjects, heart rate is expected to
rise continuously and approximately linear-
ly with work load. In healthy subjects and
athletes a slight decline of the slope can of-
ten be observed at high work rate levels, whe-
reas mainly patients with cardiac impair-
ments often show an increase of the slope.
Especially when testing patients with pace-
makers, investigators should pay close atten-
tion to a continuous increase in heart rate.
In order to assure that the subject is stressed
to a maximum and is not limited by other
Fig. 3. Oxygen uptake: Position, slope, linearity (modified accoding to Wasserman (1999)).
See text for explanation.
VIASYS info Special Edition CPET, April 2002
symptoms (e.g. pulmonary limitation), max-
imum heart rate should almost reach the
maximum predicted value (less than 10
beats).
How does heart rate rise during
exercise (Graph 5)?
exercise
Oxygen transport can be described on the
basis of Fick's Principle:
VO 2 = HR * SV * (CaO2 - CvO2).
Increasing heart rate (HR), increasing stroke
volume (SV), as well as the difference of oxy-
gen content between arterial and mixed-ve-
nous blood, (CaO2-CvO2) contribute to in-
crease V'O2. In general, all three parameters
change with increasing work load whereby
there will be an approximately linear relati-
on between heart rate and oxygen uptake in
healthy subjects. However, the lower the stro-
ke volume (e.g. in unfit or obstructive sub-
jects), the higher the basic heart rate has to
be. If no further increase in stroke volume is
possible, and if CaO2-CvO2 is already utili-
zed, there is no choice but to increase heart
rate in order to increase oxygen uptake. This
is reflected by the overproportional increase
in Fig. 4.
How does oxygen pulse rise with
increasing work load (Graph 2)?
increasing
On the basis of Fick's Principle oxygen pul-
se is obtained through division by heart rate:
O2 Pulse = V'O2/HR = SV * (CaO2 - CvO 2)
Consequently, oxygen pulse measures the
amount of oxygen that is transported by the
blood per beat and therefore directly reflects
cardiac function; if cardiac function is good,
the amount of oxygen transported per beat is
high. O2 pulse is continuously increasing dur-
ing exercise (increase in SV and in CaO2-
CvO2). In unfit or, for example obstructive
subjects, O2 pulse will continuously increase;
however, the curve trend will be lower due
to smaller stroke volume.
If cardiac function is poor or bad, the stroke
volume is already utilized at low work rate
Essay
levels so that oxygen transport per beat can
only be increased by oxygen extraction.
Since this increase is soon limited, O2 pulse
will reach a plateau as soon as maximal ex-
traction is reached. A further increase in work
rate will then consequently result in an over-
proportional increase in heart rate (see Fig.
4).
Assessment of ventilator
ventilatoryy perfor
perfor--
mance
Graph 1, 4, 7 as well as dyn. F/V -loop
F/V-loop
Does ventilation rise during exer cise
exercise
(Graph 1)?
Ventilation normally increases linearily un-
til the anaerobic threshold is reached and ri-
ses overproportionally due to the increased
amount of anaerobically produced CO2 du-
ring exercise provided that the breathing re-
serve is sufficient.
Is the ventilatory demand incr
ventilatory eased
increased
(Graph 4)?
Respiratory drive is mainly controlled by the
CO2 that has been released. A healthy sub-
ject requires an increase in ventilation by
about 20 to 25 L per additional liter of CO2.
If dead space ventilation is increased and/or
an impairment in gas exchange is present,
ventilation must be increased so that the same
amount of CO2 can be released. This graph
is discussed in detail later in relation to the
respiratory equivalents (Graph 6).
Breathing pattern, br
Breathing eathing rreserve
breathing eserve
(Graph 7)?
Depending on the breathing frequency (BF)
and tidal volume (VT) there are several pos-
sibilities to reach the same ventilation:
For example: VE=50 L/min can be reached
as follows: 50 breaths ‡ 1 L (lower isopleth)
or 20 breaths ‡ 2.5 L (upper isopleth, see
Fig. 1, Graph 7). Subjects with flow limita-
tions will try to breathe as deeply and as slow-
ly as possible, whereby the V'E curve will
be plotted along the upper isopleth. A sub-
ject with ventilatory restriction, on the other
hand, achieves maximum tidal volume quik-
kly due to his/her low VC and then ventilati-
on can only be increased by increasing brea-
thing frequency. Consequently, VT will soon
reach a plateau, move towards the lower iso-
pleth and probably intersect.
Furthermore, the measured maximum volun-
tary ventilation (MVV) and inspiratory ca-
pacity (IC) can be plotted illustrating whe-
ther the subject has reached his/her maximum
ventilation and consequently whether a ven-
tilatory limitation is present.
27
Essay
Breathing pattern, br
Breathing eathing rreserve
breathing eserve
(Dynamic F/V -loop)?
F/V-loop)?
Thanks to modern digital technology it is,
however, easier to record the dynamic flow-
volume loop during exercise in addition to
the maximum flow-volume curve at rest (see
Fig. 2). This allows you to immediately de-
termine whether a subject's ventilatory reser-
ves are sufficient or whether his/her maxi-
mum possible flow and tidal volume have
already been reached, i. e. whether he/she is
already exhausted. The evaluation of dyna-
mic flow-volume loops are discussed in de-
tail by Schwarz in Fritsch (1999) and in the
JAEGER info, Special Edition Ergo-
spirometry (1999).
Assessment of a ventilation-
perfusion mismatch
Graph 6, 4 (and 9)
Is the ventilatory demand incr
ventilatory eased
increased
(Graph 6 and 4)?
In Graph 6, the two ventilatory equivalents
for oxygen (EQO2 ª V'E/V'O2)2 and carbon
dioxide (EQCO2 ª V'E/V'CO2)3 are display-
ed. Ventilation V'E is composed of alveolar
ventilation V'A (here gas exchange takes
place) and dead space ventilation V'D:
V'E = V'A + V'D.
During exercise onset, dead space ventilati-
on is relatively high due to the low tidal vo-
lume but decreases with increasing tidal vo-
lume. This is also reflected by the trend in
ventilatory equivalents: At the beginning,
they are relatively high and decline with in-
creasing tidal volume (due to reduced dead
space ventilation and due to an improved gas
exchange).
Fig. 5: Oxygen pulse (modified acc. to
Wasserman (1999))
28
In close vicinity to the anaerobic threshold,
a healthy subject has a ventilatory demand
of approximately 20 to 25 L for one liter of
oxygen uptake or 25 to 30 L VE to release
one liter of CO2.
Both an increased dead space ventilation and
an impaired gas exchange will result in an
increased ventilation to assure an adequate
gas exchange. Consequently, the respiratory
equivalents are increased (also see Fig. 7,
Graph 6).
Dif fusion impairment or incr
Diffusion eased dead
increased
space (if rrequir
equired, Graph 9)?
equired,
There are different possibilities to differen-
tiate between an increased dead space venti-
lation and an impaired gas exchange:
Blood gases: PaO2, PaCO2
Dead space ventilation
If blood gases are taken during exercise, the
amount of dead space ventilation can be cal-
culated according to the Bohr formula:
VD/VT = (PaCO2 ñ PECO2)/PaCO2 ñVDapp/VT4
At maximum work load, this value is nor-
mally between 0.15 and 0.20, values higher
than 0.30 indicate an increased dead space
ventilation.
Alveolar -arterial
Alveolar-ar
-ar differ
terial oxygen dif ference
ference
P(A-a)O2:
A diffusion impairment can be best deter-
mined on the basis of P(A-a)O2 which is cal-
culated from blood gases and CPET data:
P(A-a)O2 = FiO2 * (BP ñ 47) ñ PaCO2 * (FiO2
+ (1-FiO2)/RER)
At rest, this value is normally between 10 to
15 mmHg; during exercise, this value is age-
dependent and is between 25 (subjects < 40
years) and 35 mmHg (> 50 years). If the
blood gas values are plotted in Graph 9 to-
gether with the values for PETO2 and PET-
CO2, this information is immediately display-
ed on the screen.
Slope and offset of ventilation
(Graph 4)?
As already mentioned, ventilation is com-
posed of V'E = V'A + V'D.
Normally, there is an increase in ventilation
of aproximately 25 liters per liter CO2. An
increased dead space ventilation will there-
fore mainly give rise to a parallel displace-
ment, whereas a disturbed gas exchange dur-
Fig. 4. Increase in heart rate with oxygen uptake
(Graph 5; for a better overview the 2. Y-axis has
been left out).
Left: Athlete (low HR, low slope); Center: un-
trained subject (increased heart rate but linear
and normal slope, finally slightly flattened);
Right: cardiac limitation (clear unproportional
slope at the end of exercise).
ing exercise will result in an increased slo-
pe5.
Consequently, evaluation of this slope has
increasingly gained importance over the last
few years, mainly with regard to the degree
of severity of the impairment, as well as re-
garding the mortality (Johnson (2000), Kle-
ber (2000), Meyer (2001)).
Determination of the aer obic-ana-
aerobic-ana-
earobic transition (A
earobic T thr
(AT eshold)
threshold)
Graph 5, 6, 8 (and 9):
What is the subject's endurance
capability?
In addition to other findings (is exercise ca-
pacity normal, at least up to AT? Is AT within
the normal range? Are impairments occuring
below AT?) this transition is of importance
mainly for diagnosing exercise capacity in
the field of endurance sports, as well as for
disability assessments. Due to the additional
anaerobically produced CO2, cardiopulmo-
nary exercise testing allows reliable deter-
mination of anaerobic threshold by non-in-
vasive methods on the basis of several re-
corded or computed parameters:
AT-determination on the basis of RER
(Graph 8):
If the CO2 release exeeds the O2 uptake (i.e.
no hyperventilation, CO2-rebreathing etc., i.e.
RER > 1) during incremental exercise tests,
the additional CO2 has to be produced anae-
robically. However, not every subject is able
to adjust his/her metabolism to combust
100% carbohydrates. Consequently, additi-
onal anaerobically produced energy has to
be provided at, for example, RER = 0.9 (of-
ten reflected by the quick increase in RER,
also see Fig. 6, bottom left).
Therefore, AT determination via RER = 1 can
only be regarded as a rough estimation and
RER = 1 as the upper limit for AT.
AT determination according to V-Slope
(Graph 5, second Y-axis):
At rest and at low work rate levels both car-
bohydrates (RER = 1.0) and fat (RER = 0.7)
are combusted (mixed combustion) so that
the ratio between oxygen uptake and carbon-
dioxide release is approximately 0.85.
This energy production is reflected by the
first linear portion (also see Fig. 6, top left).
VIASYS info Special Edition CPET, April 2002

With increasing exercise, the body tries to
improve oxygen utilization so that fat com-
bustion declines and combustion of carbo-
hydrates increases. Consequently, RER in-
creases from 0.85 towards 1.0. In other
words, more CO2 is produced per oxygen
portion. This adjustment is clearly reflected
by the first break point. At a certain work
rate level the additional oxygen amount is
still not sufficient to produce the required
amount of energy. Now the body activates
its anaerobic reserves.
Due to anaerobic metabolism, additional CO2
is released, whereby oxygen uptake is not
increased proportionally. This results in a
further increase in CO2 release as compared
to oxygen uptake reflected at the second
break point.
AT determination on the basis of EQO2
(Graph 6):
At rest and with the onset of exercise the
subject breathes shallowly. Due to the ana-
tomic dead space of 200 to 300 ml, a major
part of the ventilation doesn't reach the alve-
oli resulting in relatively high breathing equi-
valents for both O2 and CO2 (also see Fig. 6,
upper right corner).
Fig. 6. Anaerobic threshold acc. to various me-
thods: Top left: V-slope (Graph 5 - right Y-axis),
Top right: EQO2 (graph 6); Bottom left: RER
(Graph 8); Bottom right: PETO2 (Graph 9).
VIASYS info Special Edition CPET, April 2002
With increasing work load, tidal volume in-
creases resulting in a decline in relative dead
space ventilation. This is reflected by the fall
of the ventilatory equivalents. At a certain
tidal volume, which is defined by the
subject's pulmonary function, the increase in
ventilation can only be met by breathing fre-
quency. This means that from this point on
the ventilatory equivalents remain approxi-
mately constant.
Normally CO2 is responsible for respiratory
drive, the EQCO2 curve shows a constant
trend after reaching AT, while the EQO2 curve
rises due to increased ventilation. This rise
has the same cause as the second break of
the V-slope curve and can consequently be
used to determine AT as well.
The same applies to the FETO2 curve (PETO2
respectively) in Graph 9. This parameter will
also rise at AT due to hyperventilation (with
regard to oxygen - please refer to Fig. 6, bot-
tom right).
Essay
Evaluation of anaerobic thr
anaerobic eshold
threshold
Before going into details, I would like to
point out that it is often not easy or someti-
mes even impossible to determine anaerobic
threshold. Often, subjects are not able to even
reach the anaerobic threshold. Although we
are talking about a threshold, we have to re-
alize that in fact, it is a transition area. Con-
sequently, if defined by different methods,
the threshold is not always at the exactly same
point depending on the method of evalua-
tion. It is therefore recommended to simul-
taneously use all available methods and de-
fine the point which has the best possible
match with all methods (Fig. 6).
The anaerobic threshold considerably cont-
ributes to endurance capacity evaluation and
according to Wasserman, should be approxi-
mately 60% of maximum predicted oxygen
uptake. Unfortunately, this has not been ac-
cepted so far in different guidelines for
assessment (Fritsch 1999). Instead, it is still
referred to maximum oxygen uptake. Howe-
ver, this is only valid if both anaerobic thres-
holds are within the normal range and the
subject has been stressed to a maximum.
Example
As a summary of all the different parame-
ters, graphs and trends discussed above, view
the following example:
Before treatment:
Figure 7 shows the results of a patient with
valvular heart defect, aortostenosis, pulmo-
nary hypertension, as well as an exercise-in-
duced pulmonary shunt.
Fig. 7. Example
(prior to treatment);
Details see text.
29
Essay

Assessment of cardiac (cardiopulmonary)
performance
Maximum oxygen uptake: approx. 1,286 mL
Maximum V'O2 pred = 2,119 mL Î reduced
(approx. 61%)
a) V'O2: Linear, no flattening, normal slo-
pe Î yet no cardiac limitation
b) HR: Linear increase, high HR reserve
Î yet no cardiac limitation
c) HR/V'O2: Slightly above normal, unpro-
portional rise at the end Î slightly im-
paired cardiac function
c) O2 pulse: Low, still increasing oxygen
pulse Î yet no cardiac limitation but
slightly impaired cardiac function
Assessment of ventilatory performance
a) V'E: Continuous increase in ventilation
Î no ventilatory limitation
b) V'E/V'CO2: Increased ventilation (both
"offset" and slope) Î increased ventila-
tory demand
VT/V'E:
- Normal breathing pattern Î yet no
ventilatory limitation
- Dynamic F/V not available but no gra-
phical indication of any ventilatory li-
mitation
Assessment of a ventilation-perfusion-im-
pairment
a) Impairment (Graph 4 and Graph 6): the
+49 (0)931 4972-381,
hardly declining ventilatory equivalents,
which immediately rise after exercise on-
set are important.
Fig. 8: Example (post
treatment).
Details see text.
Î Suspected pulmonary shunt and dif-
fusion disorder
b) Blood gases are not available but both
Graph 4 (high slope) and Graph 6 (in-
creased, rising during exercise) rather in-
dicate a gas exchange disorder (pulmo-
nary hypertension, pulmonary shunt).
Definition of anaerobic thr
anaerobic eshold (A
threshold T)
(AT)
a) AT at approx. 993 mL
b) AT at approx. 47 % of V'O2 pred Î con-
siderably reduced
After treatment:
Although the subject was not stressed to a
maximum, it is clearly shown after treatment
(artificial valves and surgery of aortosteno-
sis) that (Fig. 8):
the lower limit of maximum oxygen
uptake is reached (85% pred)
oxygen pulse is within normal range
(96% pred)
heart rate increase is within normal ran-
ge (only a small unproportional rise can
be seen at the end)
diffusion disorder is no longer present
(EQO2 within normal range: approx. 22
at AT, even the slope in Graph 4 is low)
AT is 1,495 mL and consequently within
normal range.
Last, but not least, I would like to point out
that also the stress ECG, which is not discus-
sed in this essay, may provide important in-
formation for evaluation and interpretation.
Literature:
Literature:
1. Eschenbacher W. L., Mannina A.: An
algorithm for the interpretation of cardio-
pulmonary exercise tests.. Chest 97 (1990)
263 - 267
2. Fritsch J., Schwar
Schwarzz S.: Ergospirometrie
in der Begutachtung. Atemw Lungenkrkh
25 (1999) 117 - 137
3. Jaeger -Info: Schwarz S.: Ergspirometrie
Jaeger-Info:
in der Begutachtung. Sonderausgabe
Ergospirometrie, JAEGER (1999) 8-21
4. Johnson R. L.: Gas Exchange Efficiency
in Congestive Heart Failure. Circulation
101 (2000) 2774 - 2776
5. Jones N. L.: Clinical Exercise Testing.
Atemw Lungenkrkh 25 (1999) 117 -137
6. Kleber FF.. X., Vietzke G., Wernecke K.
D. et al.: Impairment of Ventilatory Effi-
ciency in Heart Failure. Circulation 101
(2000) 2803 - 2809
7. Meyer F F.. J., Borst M. M., Zugck C. et
al.: Respiratory Muscle Dysfunction in
Congestive Heart Failure. Circulation 103
(2001) 2153 - 2158
8. R¸hle K.-H.: Praxisleitfaden der Spiroer-
gometrie. Kohlhammer (2001)
9. Roca J., Whipp B. J. Clinical Exercise
Texting. ERS Monograph 6 (1997)
10. Schardt F ., Bedel S.: Ergospirometrie in
F.,
der arbeits- und sozialmedizinischen
Begutachtung, Sonderausgabe Ergospiro-
metrie, JAEGER (1999) 24-25
11. Wasserman K., Hansen J. E., Sue D. Y.,
Casaburi R., Whipp B. J.: Principles of
Exercise Testing and Interpretation. Lip-
pincott Williams & Wilkins, Philadelphia
(1999)
Hermann Eschenbacher, Ph.D.
Erich Jaeger GmbH
Scientific Application and Training Center
Leibnizstr. 7
D-97204 Hoechberg.
 +49 (0)931 4972-319,
eMail: he@jaeger-toennies.com

Footnotes
1
Wasserman proposes 10.3, literature gives values between 9.5 and 12; according to our experience, a value of 10.5 has proven to be suitable.
2
The exact calculation also considers apparative dead space VDapp of mask or mouthpiece, as otherwise these parameters would depend on the equipment: EQO2 = VE/VO2 - VDapp*BF/VO2
3
see note 2: analoguous for EQCO2
4
Literature also supports estimation of dead space ventilation on the basis of FETCO2. However, this is not very precise, especially in patients with ventilation-perfusion disorders.
5
This is the result of first model calculations I have perfomed; however, for manifestation, further examinations are required.

30 VIASYS info Special Edition CPET, April 2002

 The Last Page

Principles of Exercise Testing & Interpr

Exercise
Clinical Applications
etation: Including Pathophysiology and
Interpretation:
CPET Seminars
von Karlman Wasserman (Editor), James E. Hansen, Darryl Y. Sue, Richard Casaburi Jaeger regularly offers CPET semi-
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A practical guide to using gas exchange techniques in clinical and research settings, Steinh‰user, Carolina Neder
explaining exercise testing technology and its applications. After background material Texts and graphics have been compiled
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