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Departments of Internal Medicine and Anesthesiology, Mayo Clinic and Foundation, Rochester, Minnesota 55905
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ABSTRACT |
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An open-circuit (OpCirc)
acetylene uptake cardiac output (
T)
method was modified for use during exercise. Two computational techniques were used. OpCirc1 was based on the integrated
uptake vs. end-tidal change in acetylene, and OpCirc2 was
based on an iterative finite difference modeling method. Six subjects
[28-44 yr, peak oxygen consumption
(
O2) = 120%
predicted] performed cycle ergometry exercise to compare
T using OpCirc and direct Fick methods. An incremental protocol was repeated twice, separated by
a 10-min rest, and subsequently subjects exercised at 85-90% of
their peak work rate. Coefficient of variation of the OpCirc methods and Fick were highest at rest (OpCirc1, 7%,
OpCirc2, 12%, Fick, 10%) but were lower at
moderate to high exercise intensities (OpCirc1, 3%,
OpCirc2, 3%, Fick, 5%). OpCirc1 and
OpCirc2
T correlated
highly with Fick
T
(R2 = 0.90 and 0.89, respectively). There were
minimal differences between OpCirc1 and OpCirc2
compared with Fick up to moderate-intensity exercise (<70% peak
O2); however, both
techniques tended to underestimate Fick at >70% peak
O2. These differences
became significant for OpCirc1 only. Part of the differences
between Fick and OpCirc methods at the higher exercise
intensities are likely related to inhomogeneities in ventilation and
perfusion matching (R2 = 0.36 for Fick
OpCirc1 vs. alveolar-to-arterial oxygen tension difference). In conclusion, both OpCirc methods provided
reproducible, reliable measurements of
T during mild to moderate exercise. However, only OpCirc2 appeared to approximate Fick
T at the higher work intensities.
pulmonary blood flow; solubility; inhomogeneity; dead space
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INTRODUCTION |
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MULTIPLE NONINVASIVE TECHNIQUES have been developed to
assess cardiac output (
T) at rest and
during exercise. The most common include acetylene
rebreathing, carbon dioxide rebreathing, Doppler, and electrical
impedance cardiography (3, 6, 10, 13, 18, 25). Among these techniques,
the acetylene rebreathing technique has been validated against invasive
techniques and has gained wide acceptance (11, 26). A drawback to the
method, however, is the buildup of carbon dioxide as a result of
rebreathing and the resultant dyspnea. This is a particular problem at
higher intensities of exercise or with the longer rebreathe times that may be necessary when equilibration of gases is prolonged, such as in
patients with ventilation inhomogeneity (i.e., aging or obstructive
airway disease) (12). Another drawback to the acetylene rebreathing
technique is the potential change in the lung-rebreathe bag volume due
to a changing respiratory quotient and potential errors that can occur
when trying to fill the rebreathe bag with a precise volume (12).
Previous work by Stout et al. (24), Gan et al. (7), and Nielsen et al.
(16) has suggested the use of an open-circuit washin method
(OpCirc) to assess
T at rest
and during exercise. The technique is very similar to rebreathe,
requiring two inert gases, one soluble and the other essentially
insoluble, to be able to compute pulmonary blood flow and to correct
for changes in lung volume and alveolar dead space, respectively.
Because the method only requires a washin of 6-10 breaths of the
two inert gases, there is no rebreathing, and breathing remains
spontaneous (i.e., without change in breathing pattern or, in many
cases, cognition on the part of the test subject). To date, the
OpCirc method for assessing
T
has been compared with thermodilution in anesthetized, ventilated dogs
and compared with the rebreathe technique in humans (7, 16, 24). The
present investigation compares methods described by Stout et al. (24)
and Gan et al. (7) to direct Fick measurements of
T at rest and during mild through heavy
exercise in healthy humans. We propose that the OpCirc method
compares closely with invasive measurements of
T and is highly reproducible in mild
through heavy exercise.
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METHODS |
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Subjects.
All aspects of the study were approved by the Mayo Clinic Institutional
Review Board. Subjects consisted of staff clinicians or residents in
the Department of Anesthesiology who reviewed and gave written,
informed consent before participation. Usual activity levels varied
among the subjects; four subjects were former athletes and maintained a
moderate level of training during the time of the study. Before
testing, subjects were instructed to fast for at least 2 h. The
majority of studies were performed in the early morning, thus resulting
in a fasting period
8 h. Subjects were also instructed to avoid
exercise the day of testing and to avoid heavy exercise training the
day before testing.
Exercise protocol. Subjects reported to the General Clinical Research Center Exercise Core Laboratory on two occasions for exercise studies. During the first session, subjects were familiarized with the testing equipment and performed a maximal cycle ergometry test to volitional exhaustion. During the initial test, measurements were made of gas exchange (Medical Graphics CPXD), heart rate (Marquette Electronics), and power (electronically braked cycle ergometer). Power was incremented between 25 and 50 W/min, depending on the subject.
During the second session, catheters were placed in the pulmonary and radial arteries and measurements of
T
were assessed using the direct Fick and OpCirc methods.
Pulmonary artery catheters (7 Fr, 65 cm, double-lumen pulmonary artery
catheters; Arrow International, Reading, PA) were inserted via an 8-Fr
introducer catheter (Arrow International) under local anesthesia
through an antecubital vein during continuous electrocardiogram and
pressure monitoring. The correct position of the pulmonary artery
catheter was verified by the wedge position and pressure tracings.
Flexible, 20-gauge, PVC radial artery catheters were inserted
percutaneously under local anesthesia and taped in place to allow
multiple arterial blood-gas samples to be taken. Both catheters were
continuously flushed with heparinized saline (3 U/ml heparin; 3 ml/h)
to maintain patency. Measurements were obtained at rest and during
three submaximal steady-state work intensities (~20, 40, and 60% of
peak power). Each work intensity lasted 7-9 min, the time required
to reach steady state followed by two repeat sets of measurements.
After 2-3 min at constant power to allow steady state in oxygen
consumption (
O2), arterial
and mixed venous blood samples were drawn simultaneously, whereas
oxygen consumption was measured over approximately a 30-s period. This
was followed by an OpCirc measurement (8-12 breaths of
acetylene-helium gas mixture). Allowing 1-2 min at constant power
setting of the ergometer to wash out the inert gases from the
subject's lung, we repeated the measurements of
O2 and OpCirc. On
termination of the second OpCirc data collection, power
output of the ergometer was increased to the next level and the
procedures were repeated. After completion of the three submaximal work
levels, a rest period of 5-10 min was taken, and the three work
levels were subsequently repeated. When the second set of samples was completed, most subjects had an additional rest period, followed by a
final work bout at ~80-85% of the peak power achieved on their
initial exercise test. Measurements of
O2, blood sampling, and
OpCirc were taken again, similar to the submaximal work load measurements. One subject was unable to complete these last measurements.
OpCirc technique.
T was measured noninvasively using the
OpCirc inert gas washin method. The technique has been
described previously (7, 16, 24). Figure 1
shows the valve set up for the washin of inert gases. A
pneumotachograph (Hans Rudolph, Kansas City, MO, 381 series;
transducer, Celesco, ±2 cmH2O) was connected to a nonrebreathing Y valve (Hans Rudolph, 273C), whose inspiratory port was
connected to a pneumatic switching valve with low resistance and low
dead space (Hans Rudolph, P0271, controller 4285A), allowing switching
between room air and the
T gas mixture
(0.7% C2H2, 21% O2, 9% He,
balance N2) on the inspired port with minimal dead space
(<50 ml). Gases were sampled via a mass spectrometer (Perkin-Elmer, 1100), with a phase delay of 0.27 s. Throughout the resting and exercise breathing, the subjects were encouraged to breathe in a
regular rhythm, avoiding coughs, swallows, and partial breaths, if
possible. The subjects were allowed to breathe normally from the valve,
and the operator switched the pneumatic valve to change the inspiratory
air source to the
T mixture. The washin
of C2H2 and helium was observed on the computer
screen by the operator on a breath-by-breath basis, until eight breaths
had been obtained, as shown in Fig. 2. Data
analysis was performed immediately after each maneuver using the
relatively rapid calculation method (OpCirc1) described by
Gan et al. (7) and Stout et al. (24), as outlined in the
APPENDIX. In addition, data were analyzed after the
exercise session using a finite difference modeling method
(OpCirc2), also outlined in the APPENDIX. For
both techniques, we used all eight breaths. OpCirc1
calculated the uptake of C2H2, taking breath pairs, with 28 possible pairs. As a part of the data-smoothing process,
outlier solutions of the breath pairs (>98th percentile) were removed
and the
T was reaveraged.
OpCirc2 examined all breaths and included a minimization
technique to minimize differences between modeled and actual end-tidal
gas concentrations (see APPENDIX).
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Blood gases.
Mixed venous blood samples were drawn from the pulmonary artery
catheter at the same time that arterial blood was drawn from the radial
artery catheter, and measurements of
O2 were taken. The blood
samples were analyzed for oxygen content using an IL 1306 co-oximeter
and blood gases (PO2,
pH, and PCO2) were
analyzed by using an IL 482 blood-gas analyzer.
T was then determined using Fick
(
O2 =
T × arteriovenous oxygen
difference). All blood samples were collected anaerobically, agitated,
and immediately chilled in crushed ice before analysis (usually within 5-10 min of collection). The co-oximeter and blood-gas analyzer were calibrated with standards over the broad range of oxygen and
carbon dioxide values expected during the studies. An in-dwelling, fast-response thermocouple at the end of the pulmonary artery catheter
was used to assess temperature changes during exercise for correcting
the blood-gas values before calculation of
T.
Data analysis.
T at each work intensity was
calculated using OpCirc1 and OpCirc2 methods for
each subject. Each subject had four data points per work level, except
at the highest work intensities, where only two data points were
available. This included repeat measurements of
O2 and
T during each of two exercise sessions
at the lower work intensities and repeat measurements during one
exercise session for the highest work intensity. For each subject, all
data points were submitted to least squares regression using the
equation
T = K0
+
O2 × K1 +
O22 × K2, where K0,
K1, and K2 are the intercept,
linear term, and squared term coefficients, respectively. From the
regression data on each subject,
T was
estimated at fixed levels of
O2, and the interpolated
data were averaged for all subjects. The fit was very good
(R2 > 0.97 for OpCirc,
R2 > 0.93 for Fick). Paired t-tests were
applied to the interpolated data to test for differences in techniques
(P < 0.05).
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RESULTS |
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Subject characteristics.
Five male subjects and one female subject were tested. Four of the
subjects were moderately active, typically running or cycling several
times per week. The peak
O2 obtained from the
initial cycle ergometry test averaged 120% of age predicted. Peak
heart rate averaged 102% of age predicted.
Other characteristics of the group are also
shown in Table 1.
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OpCirc vs. Fick measurements of
T.
Figure 3 shows identity plots of
OpCirc1 (A) and OpCirc2 (B) vs.
Fick for all values obtained on all subjects. Each subject typically
had four data points per work intensity, except at rest and at the
highest work intensity, for which only two data points were obtained
per subject. R2 values for OpCirc1 and
OpCirc2 vs. Fick for the entire data set were 0.90 and 0.89, respectively. The mean differences (±SD) between techniques were
1.5 ± 2.0 and
0.5 ± 1.9 l/min for
OpCirc1 vs. Fick and OpCirc2 vs. Fick,
respectively.
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O2). However, OpCirc1 (but not OpCirc2) was less than Fick
(P < 0.05) over the highest two work intensities (71 and 91%
of peak
O2). Figure 4 shows the OpCirc1 and
OpCirc2 data relative to direct Fick measurements at
interpolated
O2 values.
OpCirc1 was less than Fick between
O2 of 3.5 and 4.5 l/min
(P < 0.05), but no significant differences were noted
otherwise. Therefore, the OpCirc2 calculation method more
closely tracked Fick
T
measurements with heavy exercise.
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Reproducibility of
T measurements.
Within-session (a given work intensity) and between-session (repeat
work intensity after a period of rest) coefficients of variation (CV)
of OpCirc1, OpCirc2, Fick, and
O2 are shown in Table
3. The greatest variability for all
measurements was observed at rest. The within-session and
between-session CV for OpCirc1 and OpCirc2 averaged
<4% for all work intensities and were similar to or less than the
mean CV observed for Fick and
O2 at each work intensity
(Table 3). The reproducibility of OpCirc1 and OpCirc2 was comparable in both within- and between-session
measurements at all work intensities. Thus it did not appear that one
calculation method was superior in regards to reproducibility.
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1-4% at the lower work intensities and
between 1 and 6% with moderate exercise. Repeat measurements with
different sessions were not available for the heaviest work intensities.
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DISCUSSION |
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The focus of the present investigation was to compare the
OpCirc washin technique using acetylene to the direct Fick
method for determination of
T at rest and
during exercise. We used two computational techniques,
OpCirc1 and OpCirc2, to quantify the uptake of
acetylene and to account for changes in lung volume, dead space
ventilation, and breath-by-breath variability. We found that both
methods compared favorably with direct Fick measurements of
T, particularly at light to moderate
exercise intensities. There was a tendency for both OpCirc1
and OpCirc2 to underestimate Fick at the higher work
intensities; however, this only reached significance using the
OpCirc1 method. Both OpCirc1 and OpCirc2 were found to be highly reproducible, particularly during exercise.
Computational techniques and assumptions.
Both computational methods are based on a simplified conceptual model
of the lung that includes a single dead space compartment and a single
well-mixed gas-exchanging compartment, the "alveolus." Modeling
studies and studies in challenged or diseased lungs of animals and
humans have shown that both ventilation inhomogeneity and
ventilation-to-perfusion ratio
(
A/
)
mismatching will cause
T and lung volumes
to be underestimated using rebreathing (4, 14, 19) and OpCirc
techniques (16). Acetylene uptake is dependent on lung perfusion, which
essentially carries the acetylene away from the lungs; however,
acetylene can only be carried away as delivered via ventilation. Thus
the technique is clearly dependent on the ventilation-to-capillary
perfusion ratio (
A/
c).
Any gas uptake measure will be affected by
A/
c inhomogeneity, leading to underestimation of blood flow. If the test gas is delivered from the ventilation side, the technique will give more information about high
A/
c regions
and could miss information about low
A/
c regions, whereas
techniques that deliver the gas by blood (e.g., multiple inert-gas
elimination technique) will obtain good information about
low
A/
c
regions. Further study is needed to settle this issue. In other words,
the OpCirc technique will, effectively, see low
A/
c regions as shunt
and may underestimate
T.
A/
inhomogeneity increases with exercise (8), although the cause of this
increase is not fully known. In our studies, most subjects showed an
increase in alveolar-to-arterial oxygen tension difference
(A-aDO2), consistent
with an increase in
A/
inhomogeneity (Table 2), although diffusion limitation and shunt cannot
be ruled out. There was a significant correlation between
A-aDO2 and the
Fick-OpCirc difference for OpCirc1, but not for
OpCirc2 as shown in Fig. 5.
However, a correlation with OpCirc2 may be evident with more
subjects, as there were three outliers that reduced the correlation in
the present study. We conclude from these considerations that it is likely that the OpCirc method may underestimate
T in the presence of
A/
inhomogeneities,
possibly reducing its usefulness in presence of pulmonary disease (14).
Further work is necessary to explore this in patients with obstructive
airway changes and known
A/
abnormalities.
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T may be shunted away from the gas
exchange units of the lung (through the thebesian and bronchial
circulations), and it has been proposed that this may contribute to a
substantial portion of the widened A-aDO2
during exercise. The influence of the shunt becomes particularly significant at the reduced mixed venous
PO2 observed during
heavy exercise (8). Right-to-left shunts will typically be measured by
the Fick method but not by measurements of pulmonary blood flow with
gas uptake techniques such as OpCirc with acetylene. Regions
of the lung that have perfusion but no or little ventilation (low or
zero
A/
c),
would also give an effective right-to-left shunt. Left-to-right shunts
are less common but could occur with a patent foramen ovale depending
on the cardiac pressure gradients. However, the left-to-right shunts
would be measured by both the Fick and acetylene methods for assessing
T.
The computational methods of both Stout et al. (24) and Gan et al. (7)
make a number of additional simplifying assumptions, most importantly,
an estimate of soluble gas uptake at the capillary during the breath
cycle that involves two such assumptions. The first is that alveolar
gas concentration during the inspiratory phase of the breath cycle is
obtained by linear interpolation of end-expiratory points from the
previous and current breaths; the second is that driving pressure for
diffusion is constant during inspiratory and expiratory phases of the
breath. Because of the increasing rate of absorption of soluble gas as
O2 and
T increase, this approximation could lead
to errors in
T estimation at high
levels of exercise. Our more complete computational method (OpCirc2) used all data points acquired at 8-ms intervals and thus did not include this approximation. The results from this method
were closer to Fick
T measurements at the
high intensities of exercise, and, in fact, the statistics were not
significantly different from the Fick method. The disadvantage of this
technique is its computational complexity, requiring several minutes of computer time for each analysis. However, it appears to be more accurate at higher intensities of exercise.
The gas solubility used in calculations is a critical assumption. We
used the values found by Cander (5) for blood and tissue [0.74
and 0.76 ml C2H2
(STPD) · ml
blood
1 · atm
1,
respectively]. Because solubility is a function of lipid and cell
content of the blood, it would ideally be determined at the time of the
study on each subject, potentially improving the accuracy of the method
(5, 9).
Because the OpCirc method critically depends on the
measurement of gas uptakes per breath, the time delay between gas
concentration signals and flow measurements must be accurately
determined so that the two signals may be properly aligned in time
(21). By adjusting this parameter in the analysis program, we found
that
T would be underestimated if the
time delay were underestimated. The time delay can be obtained in
individual subjects by having them perform a rapid inspiratory maneuver
after a prolonged expiration. At onset of inspiration, gas
concentration should remain at the end-expiratory value until the dead
space of the breathing valve has been cleared by the inspired gas,
after which gas concentrations should abruptly increase to the inspired
value. The time delay we used, 0.27 s, was obtained by averaging time
delays from a number of laboratory personnel who performed the rapid
inspiratory maneuver during preliminary experiments and was confirmed
by spot checking during the course of the study.
Another important determinant of the calculation of
T using the OpCirc
technique was the time response characteristics of the acetylene
channel of the mass spectrometer. Clearly, a slow response time will
result in an underestimation of
T,
especially at the higher frequencies of breathing. The 10-90%
rise time of our transient was ~0.06 s. We included a correction for
the slow rise time of our mass spectrometer that was described by Gan
et al. (7). This potential error was tested in preliminary studies by
having subjects breathe at two frequencies (30 and 60 breaths/min) at a
given work intensity. In a small number of subjects,
T did not fall with the higher breathing
frequency and was, in fact, slightly augmented, consistent with
increased work of breathing (1).
Advantage of the OpCirc technique relative to rebreathe,
breath hold, and vital capacity maneuvers.
Previous studies have found a good correlation between the rebreathe
method for the determination of
T
relative to invasive measurements in animals and humans at rest and
during exercise (11, 15, 17). Similarly, in a limited study performed
at rest,
T assessed by a single
vital capacity breath of acetylene followed by a slow complete
exhalation compared favorably to thermodilution measurements (23).
However, the washin technique offers several advantages over these
methods. Significant problems during rebreathing are the buildup of
carbon dioxide, especially during heavy exercise, and the difficulty of
matching the rebreathe tidal volume to the patient tidal volume without
inhibiting breathing. In addition, subjects are often asked to
transiently alter breathing patterns during rebreathing (augment
breathing, breathe deeper or faster), which likely alters
T, especially in some patient
populations. There are also potential errors during rebreathing
because of a change in bag volume over time due to a changing
relationship between carbon dioxide production and
O2
(
CO2/
O2),
unless two tracer gases are simultaneously evaluated (12). Similarly, the vital capacity maneuver or a breath hold followed by a slow expiration may introduce errors due to alterations in intrathoracic pressure and is difficult to perform during exercise. In contrast, using the OpCirc method, subjects are switched into a large
reservoir containing the gas mixture without altering gas exchange or
breathing pattern. In most of our studies, subjects were switched into
the
T gas mixture with little or no
awareness, even near maximal exercise.
A/
inhomogeneity. In
both methods, a well-mixed, constantly inspired concentration of gas is
inhaled with each breath. Inspired gas is delivered to well-ventilated regions, and the exhaled concentration is a weighted average of concentrations from all lung units contributing to ventilation.
Previous studies using the OpCirc method.
Becklake et al. (2) examined the use of steady-state N2O
uptake after washin was complete and compared this to a dye dilution estimate of
T during light and moderate
steady-state exercise. By using this technique, a repeat value
generally ran within 20% of the initial measurement and compared
favorably to the dye dilution estimates of
T (<20%) difference. The present
OpCirc method offers several advantages over the methods
described by Becklake et al. (2). It does not require steady-state
conditions, no assumptions are made about the magnitude of the lung
volumes, and blood flow may be determined in the presence of
breath-by-breath changes in functional residual capacity (FRC). In
addition, the method variance is likely reduced using
C2H2, instead of N2O, as the
soluble gas, because the smaller solubility coefficient of
N2O decreases the slope of the disappearance curve, making it slightly more susceptible to experimental noise.
T but refined them by adding several
smoothing techniques. The two smoothing methods described by Gan et al.
(7), which we used for OpCirc1, included smoothing the
end-tidal gas concentrations during washin by fitting to a polynomial
and a method for culling out outliers obtained by solving all pairs of
breaths for
T and tissue volume. After
the outlier points were excluded, average
T from all possible remaining pairs of
solutions were reported. An additional smoothing technique described by
Gan et al. (7), but not used in the present study, effectively reduces
noise in gas uptake measurements caused by breath-by-breath variations in inspiratory and expiratory volumes. Instead, we included the measured differences between inspiratory and expiratory volumes in our
calculations. It is not clear if the differences in calculation methods
of Gan et al. (7) and our OpCirc1 technique would have any
impact on accuracy or reproducibility of the technique.
Unlike the OpCirc1 method, our OpCirc2 has not been
previously described. For the OpCirc2 method, each data point
acquired every 8 ms was used to calculate gas uptake at the alveolar
level in a homogenous lung model that included measured dead space (see APPENDIX). We developed this model to determine if the
simplifying assumptions behind the OpCirc1 method had an
impact on calculated
T, particularly at
high exercise intensities, for which gas uptakes are larger. We found
that OpCirc2 was not significantly different from Fick
T, even at high exercise intensities,
whereas OpCirc1 results were lower. This suggests that
nonlinearities in the OpCirc1 solution become important as
gas fluxes increase with exercise. However, further work would be
needed to prove this point. It must be stressed that even the
OpCirc2 method assumes homogenous gas distribution;
therefore, calculated
T may be affected
by
A/
c mismatch in
subjects with lung disease, similar to what has been shown for
T determined by the rebreathe technique (14, 19).
More recently, Nielsen et al. (16) compared the washin technique with
rebreathing in 10 healthy subjects. They found reproducibility of the
OpCirc method to be less than the rebreathe method. Although we did not directly compare OpCirc to rebreathe, the CV in
OpCirc reported here is less than one-half of that reported
by Nielsen et al. (16) and is comparable to or slightly less than what we have reported for rebreathe in other studies (22). We do not have an
explanation for the difference in reproducibility between our data and
that of Nielsen et al. (16), although with our experiences in both
rebreathe and OpCirc, we feel that OpCirc is
equivalent to or better than rebreathe for assessment of
T during moderate to heavy exercise.
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APPENDIX |
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Definitions of symbols and terms in the APPENDIX are found in the glossary.
Glossary
| Vti | Tissue volume; static volume that acetylene dissolves in |
c |
Pulmonary capillary blood flow |
| VnAcet, VnHe | Uptake volumes of acetylene and helium (ml, STPD), respectively, for the nth breath of the washin maneuver. These are obtained by integrating the gas concentration × flow × time product for each 8-ms sample over each breath |
| RVnAcet, RVnHe | Residual volumes of acetylene and helium, respectively, left in the lungs due to difference between inspired and expired volume of the nth breath |
| FnE,Acet, FnE,He | End-expiratory fractional concentrations of acetylene and helium respectively, for the nth breath |
![]() |
Mixed expired fractional concentraion of helium, obtained by integrating helium concentration and expiratory flow |
| FnA,Acet, FnA,He | Fractional concentrations of alveolar gas for acetylene and helium, respectively. In practice, alveolar gas concentrations were obtained from end-expiratory results |
| PB | Barometric pressure (mmHg) |
t,Acet, b,Acet |
Tissue and blood solubilities of acetylene, respectively. Although
these two terms were carried through in the derivation, in practice the
same value, 0.74 ml · ml
tissue 1 · atm 1,
was used for both
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| TnI, TnE | Inspiratory and expiratory times, respectively, of the nth breath |
| VSD,VD,vlv | Volume of serial dead space and volume of the breathing valve (ml) |
| VA | Alveolar volume |
OpCirc1
Mass balance principles are applied to both acetylene and helium uptake. With each breath, the amount leaving the lungs on expiration subtracted from the amount that entered on inspiration must equal the increase in concentration in the gas and tissue spaces plus the amount taken up by the blood. This leads to a system of three equations with two unknown parameters representing Vti and
c (7)
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(1) |
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(2) |
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(3) |
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(4) |
,Acet is the mixed venous fraction concentration of
acetylene, estimated from end-expiratory fractional concentration of
the breath immediately preceding start of washin.
The quantity KEE is a ratio of end-tidal concentration differences of
breaths n and n
1
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(5) |
n is an approximation of the
mean alveolar concentration of acetylene over the inspiratory portion
of the breath
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(6) |
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(7) |
These VSD values are only averaged for breaths with an end-expiratory value <90% of the inspiratory value to avoid an unstable solution due to small numbers in the denominator.
Two data-smoothing techniques outlined by Gan et al. (7) were used in the calculations. First, the end-expiratory gas concentrations for each breath were adjusted slightly by fitting end-expiratory concentrations vs. time to a third- or fourth-order polynomial equation, and then replacing each value with the value calculated from the equation. This process was justified by Gan et al. (7) by pointing out that the end-tidal concentrations vs. time should follow an exponential approach to an equilibrium value. From Taylor's theorem, an exponential curve can be approximated by a polynomial series. Second, in calculating the uptake volumes of each gas by integrating flow and gas concentration over the breath, the response of the gas analyzer (mass spectrometer) was corrected using a first-order differential correction.
With values for zn,
un, and vn
calculated for each breath, pairs of breaths are solved using Eq. 1 to find a solution for Vti and
c for each
pair, producing a list of n × (n
1)
solutions, where n = total number of breaths. The mean and
standard deviation are then found for the set of solutions, outlying
solutions (>98th percentile) are removed, and the average is retaken.
This process of culling out outliers is only performed once.
OpCirc2
This technique is more involved computationally, but results in a more precise solution. The lungs are considered to be one well-mixed alveolar compartment separated from the inhaled gas bag by an anatomic dead space. Gas transport in each unit of time,
t (the 8-ms
sampling period of the data), is governed by the following mass balance
considerations at the alveolar level.
The total acetylene volume in the alveolar compartment is given by
VAcet = FA,Acet × (VA +
t,Acet × Vti). The change in the acetylene volume per unit time is equal to the rate of
disappearance into the blood plus the amount entering the alveolar volume by inspiring via the anatomic dead space
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(8) |
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(9) |
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This finite difference equation is used at each time-sampling increment
to update the fractional concentration of acetylene. The helium
concentration is treated similarly, except that
t,He = 0 (negligible tissue solubility for helium).
The process starts with a calculation of VSD, as above, and
VA, as follows
|
(10) |
A computer algorithm then sets up a dead space volume that consists of
an ordered list of 1-ml units, the total volume equaling VSD. The VA and each VSD element is
initially filled with gas concentration equal to expired concentration
of the breath immediately before the start of the washin maneuver,
simulating end expiration. The computer then samples the first
inspiratory data point, obtaining volume change,
V, and values for
gas concentration at the mouth from the raw data stream. At the mouth
end of the dead space, the first m =
V dead
space elements are set to the measured gas concentration. At the
alveolar end of the dead space, m elements are each added to
the alveolar space, using Eq. 9 to update the alveolar
concentration and increasing alveolar gas volume by
V. As the
process continues during inspiration, a front of gas moves through the
dead space elements until inspired gas appears at the alveolar end of
the dead space. Further inspiration adds inspired gas to the alveolar
compartment. During expiration, Eq. 9 is again applied and the
dead space elements are filled from the alveolar end with the current
value for alveolar gas concentration. This process continues until the
entire data stream has been used, and end-tidal values for each of the
breaths is obtained from the model. The sum of squared differences
between measured and modeled end-tidal concentration is obtained for
use in an iterative search procedure that finds the best
and Vti.
Taylor minimization (20) was used to find the best combination of Vti
and
that minimized the sum of squared errors
between modeled and actual end-tidal gas concentrations. Imagine a
three-dimensional surface shaped like a large bowl with the value for
sum squared errors as the height above a plane defining the ranges of
values for Vti and
. The algorithm finds the low
point of this surface (bottom of bowl) by finding its local slope and
descending the steepest path down the slope to the minimum. This
process generally took 50-100 steps. A typical solution is shown
in Fig. 6. The solution for Vti was occasionally
unphysiological, and we were unable to find methods resulting in
consistently reasonable values for it. The solution for
usually appeared reasonable despite the occasional
unstable values for Vti. Thus Vti values were not reported in this
study.
|
| |
ACKNOWLEDGEMENTS |
|---|
We thank Kathy O'Malley, Cathy Swee, and Darrell Loeffler for technical help during the study; Drs. Bradley Narr and David Seamans for expertise in placing catheters and blood-gas sampling; and Audrey Schroeder for preparation of the manuscript.
| |
FOOTNOTES |
|---|
Support for the study included The Mayo Foundation, Human Health Services Grant MO1-RR00585, General Clinical Research Centers, Division of Research Resources, and National Heart, Lung, and Blood Institure Grants HL-52230 and HL-46493.
The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.
Address for reprint requests and other correspondence: B. D. Johnson, Div. of Cardiovascular Diseases, Baldwin 2B, CVHC, Mayo Clinic and Foundation, Rochester, MN 55905 (E-mail: johnson.bruce{at}mayo.edu).
Received 22 August 1999; accepted in final form 5 January 2000.
| |
REFERENCES |
|---|
|
|
|---|
1.
Aaron, EA,
Seow KC,
Johnson BD,
and
Dempsey JA.
Oxygen cost of exercise hyperpnea: implications for performance.
J Appl Physiol
72:
1818-1825,
1992
2.
Becklake, MR,
Varvis CJ,
Pengally LD,
Kenning S,
McGregor M,
and
Bates DV.
Measurement of pulmonary blood flow during exercise using nitrous oxide.
J Appl Physiol
17:
579-586,
1962
3.
Bogaard, HJ,
Hamersma WB,
Horsch JL,
Woltjer HH,
Postmus PE,
and
de Vries PM.
Noninvasive assessment of cardiac output during exercise in chronic obstructive pulmonary disease: comparison of the CO2-rebreathing method and electrical impedance cardiography.
Physiol Meas
18:
327-338,
1997[Web of Science][Medline].
4.
Burma, GM,
and
Saidel GM.
Pulmonary blood flow and tissue volume: model analysis of rebreathing estimation methods.
J Appl Physiol
55:
205-211,
1983
5.
Cander, L.
Solubility of inert gases in human lung tissue.
J Appl Physiol
14:
538-540,
1959
6.
Espersen, K,
Jensen EW,
Rosenborg D,
Thomsen JK,
Eliasen K,
Olsen NV,
and
Kanstrup IL.
Comparison of cardiac output measurement techniques: thermodilution, Doppler, CO2-rebreathing and the direct Fick method.
Acta Anaesthesiol Scand
39:
245-251,
1995[Web of Science][Medline].
7.
Gan, K,
Nishi I,
Chin I,
and
Slutsky AS.
On-line determination of pulmonary blood flow using respiratory inert gas analysis.
IEEE Trans Biomed Eng
40:
1250-1259,
1993[Web of Science][Medline].
8.
Gledhill, N,
Froese AB,
Buick FJ,
and
Bryan AC.
A/
inhomogeneity and A-aDO2 in man during exercise: effect of SF6 breathing.
J Appl Physiol
45:
512-515,
1978
9.
Grollman, A.
The solubility of gases in blood and fluids.
J Biol Chem
82:
317-325,
1929
10.
Hopman, MT,
Oeseburg B,
and
Binkhorst RA.
Cardiac output determined by the CO2 rebreathing method during arm exercise.
Clin Physiol
14:
37-46,
1994[Web of Science][Medline].
11.
Hsia, CC,
Herazo LF,
Ramanathan M,
and
Johnson RL, Jr.
Cardiac output during exercise measured by acetylene rebreathing, thermodilution, and Fick techniques.
J Appl Physiol
78:
1612-1616,
1995
12.
Johnson, BD,
Seow KC,
Pegelow DF,
and
Dempsey JA.
Adaptation of the inert gas FRC technique for use in heavy exercise.
J Appl Physiol
68:
802-809,
1990
13.
Julius, S.
Validation of noninvasive measurement of cardiac output. The Ann Arbor experience.
Eur Heart J
11:
144-147,
1990.
14.
Kallay, MC,
Hyde RW,
Smith RJ,
Rothbard RL,
and
Schreiner BF.
Cardiac output by rebreathing in patients with cardiopulmonary diseases.
J Appl Physiol
63:
201-210,
1987
15.
Liu, Y,
Menold E,
Dullenkopf A,
Reissnecker S,
Lormes W,
Lehmann M,
and
Steinacker JM.
Validation of the acetylene rebreathing method for measurement of cardiac output at rest and during high-intensity exercise.
Clin Physiol
17:
171-182,
1997[Web of Science][Medline].
16.
Nielsen, OW,
Hansen S,
and
Gronlund J.
Precision and accuracy of a noninvasive inert gas washin method for determination of cardiac output in men.
J Appl Physiol
76:
1560-1565,
1994
17.
Nystrom, J,
Celsing F,
Carlens P,
Ekblom B,
and
Ring P.
Evaluation of a modified acetylene rebreathing method for the determination of cardiac output.
Clin Physiol
6:
253-268,
1986[Web of Science][Medline].
18.
Pianosi, P,
and
Garros D.
Comparison of impedance cardiography with indirect Fick (CO2) method of measuring cardiac output in healthy children during exercise.
Am J Cardiol
77:
745-749,
1996[Web of Science][Medline].
19.
Pierce, RJ,
McDonald CF,
Thuys CA,
Rochford PD,
and
Barter CE.
Measurement of effective pulmonary blood flow by soluble gas uptake in patients with chronic airflow obstruction.
Thorax
42:
604-614,
1987
20.
Press, W,
Flannery B,
Taukolsky S,
and
Vettering W.
Numerical Recipes: The Art of Scientific Computing. Cambridge, MA: Cambridge Univ. Press, 1986.
21.
Proctor, DN,
and
Beck KC.
Delay time adjustments to minimize errors in breath-by-breath measurement of
O2 during exercise.
J Appl Physiol
81:
2495-2499,
1996
22.
Proctor, DN,
Beck KC,
Shen PH,
Eickhoff TJ,
Halliwill JR,
and
Joyner MJ.
Influence of age and gender on cardiac output-
O2 relationships during submaximal cycle ergometry.
J Appl Physiol
84:
599-605,
1998
23.
Sadeh, JS,
Miller A,
and
Kukin ML.
Noninvasive measurement of cardiac output by an acetylene uptake technique and simultaneous comparison with thermodilution in ICU patients.
Chest
111:
1295-1300,
1997
24.
Stout, RL,
Wessel HU,
and
Paul MH.
Pulmonary blood flow determined by continuous analysis of pulmonary N2O exchange.
J Appl Physiol
38:
913-918,
1975
25.
Triebwasser, JH,
Johnson RL,
Burpo RP,
Campbell JC,
Reardon WC,
and
Blomqvist CG.
Noninvasive determination of cardiac output by a modified acetylene rebreathing procedure utilizing mass spectrometer measurements.
Aviat Space Environ Med
48:
203-209,
1977[Medline].
26.
Warburton, DE,
Haykowsky MJ,
Quinney HA,
Humen DP,
and
Teo KK.
Reliability and validity of measures of cardiac output during incremental to maximal aerobic exercise. Part I: conventional techniques.
Sports Med
27:
23-41,
1999[Web of Science][Medline].
27.
Yeh, MP,
Gardner RM,
Adams TD,
and
Yanowitz FG.
Computerized determination of pneumotachometer characteristics using a calibrated syringe.
J Appl Physiol
53:
280-285,
1982
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