Vol. 90, Issue 2, 538-544, February 2001
Steady-state measurement of NO and
CO lung diffusing capacity on moderate exercise in
men
Colin
Borland1,
Bryan
Mist2,
Mariella
Zammit3, and
Alain
Vuylsteke3
1 Department of Medicine, Hinchingbrooke Hospital,
Huntingdon, Cambridgeshire PE18 8NT; 2 Department of
Cardiological Sciences, St George's Hospital Medical
School, Cranmer Terrace, Tooting, London SW17 0RE; and
3 Anaesthetic Department, Papworth Hospital, Papworth
Everard, Cambridge CB3 8RE, United Kingdom
 |
ABSTRACT |
Using a rapidly responding nitric
oxide (NO) analyzer, we measured the steady-state NO diffusing capacity
(DLNO) from end-tidal NO. The diffusing
capacity of the alveolar capillary membrane and pulmonary capillary
blood volume were calculated from the steady-state diffusing capacity
for CO (measured simultaneously) and the specific transfer
conductance of blood per milliliter for NO and for CO. Nine men were
studied bicycling at an average O2 consumption of 1.3 ± 0.2 l/min (mean ± SD). DLNO was
202.7 ± 71.2 ml · min
1 · Torr1 and
steady-state diffusing capacity for CO, calculated from end-tidal (assumed alveolar) CO2, mixed expired CO2, and
mixed expired CO, was 46.9 ± 12.8 ml · min1 · Torr1. NO dead
space = (VT × FENO 
VT × FANO)/(FINO FANO) = 209 ± 88 ml, where
VT is tidal volume and FENO,
FINO, and FANO are mixed exhaled, inhaled, and alveolar NO concentrations, respectively. We used the Bohr equation to estimate CO2 dead space from
mixed exhaled and end-tidal (assumed alveolar) CO2 = 430 ± 136 ml. Predicted anatomic dead space = 199 ± 22 ml. Membrane diffusing capacity was 333 and 166 ml · min1 · Torr1 for NO
and CO, respectively, and pulmonary capillary blood volume was 140 ml.
Inhalation of repeated breaths of NO over 80 s did not alter
DLNO at the concentrations used.
alveolar capillary gas diffusion; dead space; membrane diffusing
capacity; lung capillary blood volume
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INTRODUCTION |
THEORETICALLY,
nitric oxide (NO) is the ideal gas to study lung diffusion because it
is poorly soluble in water and, because of its very rapid and virtually
irreversible reaction with Hb, its uptake is independent of pulmonary
capillary blood flow and rate of chemical reaction (6).
Our laboratory (4) originally developed a single-breath
method for measuring lung NO diffusion (DLNOSB) during breath holding at
rest. By including CO in the inspired mixture, it is possible
to simultaneously measure the
DLCOSB. From knowledge of the water
solubility and molecular weight of the two gases and by assuming that
Roughton and Forster's model also applies to NO lung transfer, our
laboratory (3) and others (8) have estimated
the Dm and Vc from a single breath. The availability of rapidly
responding and sensitive NO analyzers now allows estimation of alveolar
NO concentrations from end-expiratory samples and hence measurement of
steady-state DLNO
(DLNOSS) during tidal breathing
using safe and stable NO concentrations.
These measurements are important for several reasons. NO is
produced in high concentration (11) in the nose and taken
up in the lung, so steady-state NO gas transfer takes place during everyday life and knowledge of DLNO is
essential for understanding normal NO metabolism. Measuring diffusing
capacity in animals and on maximal exercise in humans is easier using a
steady-state method compared with a single-breath technique. Using
Roughton and Forster's method for obtaining Dm and Vc from
DLCO during steady-state breathing at two or
more O2 tensions is likely to overestimate the
O2-dependent resistance (1/
CO Vc) due to
hyperoxia increasing regional inhomogeneity in diffusing
capacity. Using DLNO and
DLCO at a single, physiological value for
PcO2 obviates this problem. Exhaled NO is
being investigated as a test for inflammatory markers in lung disease.
An increase in FENO could result from increased
NO production or from reduced DLNO
(10). Ill or ventilated patients will be unable to perform
single exhalations from total lung capacity, so knowing
DLNOSS is important in
interpreting values for FENO derived from tidal
breathing measurements. Finally, inhaled NO is being used
therapeutically to treat acute respiratory distress syndrome and
pulmonary hypertension. NO causes ultrastructural oxidant lung injury
when inhaled in concentrations of 6 ppm for 6 wk (12), and
its safety depends on its fast removal into the pulmonary capillary
blood before oxidation to nitrogen dioxide or other toxic products can
occur. If patients have reduced
DLNOSS, then toxicity may be
enhanced and the inhaled NO concentration may need to be reduced.
For these reasons, we have made combined
DLNOSS and
DLCOSS measurements in healthy
volunteers by adapting the method of Bates et al. (1).
Glossary
| NO |
Nitric oxide [parts per billion (ppb)]
|
| DL |
Lung diffusing capacity
|
| DLNO |
Diffusing capacity for NO
|
| DLCO |
Diffusing capacity for CO
|
| DLCOSS |
Steady-state diffusing capacity for CO
(ml · min1 · Torr1)
|
| DLNOSS |
Steady-state diffusing capacity for nitric oxide
(ml · min1 · Torr1)
|
| DLCOSB |
Single-breath diffusing capacity for CO
(ml · min1 · Torr1)
|
| DLNOSB |
Single-breath diffusing capacity for NO
(ml · min1 · Torr1)
|
| VT |
Tidal volume (liters)
|
| VA |
Alveolar volume (liters)
|
| RR |
Respiratory rate (min1)
|
| PB |
Barometric pressure (Torr)
|
| NO |
Specific transfer conductance of blood per milliliter for NO
(ml · min1 · Torr1 · ml1)
|
| CO |
Specific transfer conductance of blood per milliliter for CO
(ml · min1 · Torr1 · ml1)
|
| FACO2 |
Alveolar CO2 concentration (%)
|
| FECO2 |
Mixed exhaled CO2 concentration (%)
|
| FECO |
Mixed exhaled CO concentration (%)
|
| FICO |
Inhaled CO concentration (%)
|
| FINO |
Inhaled NO concentration (ppb)
|
| FENO |
Mixed exhaled NO concentration (ppb)
|
| FANO |
Alveolar NO concentration (ppb)
|
| VD |
Dead space (ml)
|
| Dm |
Diffusing capacity of alveolar capillary membrane
(ml · min1 · Torr1)
|
| Vc |
Pulmonary capillary blood volume (ml)
|
| PcO2 |
Partial pressure of O2 in pulmonary capillaries (Torr)
|
 O2 |
O2 uptake (l/min)
|
| Hb |
Concentration of hemoglobin in venous blood (g/dl)
|
| COHb |
Concentration of carboxyhemoglobin venous blood (%)
|
| metHb |
Concentration of methemoglobin in venous blood (%)
|
| |
METHODS |
Subjects
Nine nonsmoking male subjects with no history of lung disease
volunteered for the study. All signed consent forms approved by the
Huntingdon district ethics committee, who also gave approval for this
study. Their characteristics and
DLCOSB measured by the standard
technique at rest (6) are listed in Table
1. All subjects pursued a moderately
active lifestyle.
General Method
On a daily basis, temperature and PB were measured
by use of a metabolic cart (2900Z, Sensor Medics EME, Brighton, Sussex, England) calibrated against a mercury thermometer and the local meteorological office, respectively. PB was corrected for
saturated vapor pressure by reference to a table (6). Each
subject performed one complete maneuver. Background atmospheric NO,
CO2, and CO were measured. Each subject sat breathing air
on an electronically braked bicycle ergometer (Sensor Medics 800S) and
started to cycle, gradually building up speed until he achieved the
desired level of moderate exercise (~1 l/min
O2). Once steady state was achieved, exhaled air was collected for a 2-min period to measure NO and CO back
tension, and an 80-s record was also taken of intrabreath NO and
CO2 recording at the lips by arranging a fine-bore cannula within the mouthpiece to ensure zero dead space. They were then switched to a mixture of ~5,000 ppb NO and 0.1% CO in air stored in
a 200-liter Douglas bag (PK Morgan, Gillingham, Kent, UK) prepared immediately before each replicate. A continuous 2-min collection of exhaled air was made from a similar Douglas bag attached to the
exhaled port of the metabolic cart. VT on a
breath-by-breath basis, RR, and O2 were
recorded during this time from the metabolic cart. Volume was
calibrated by using a 3-liter syringe. The O2 analyzer of
the metabolic cart was calibrated using three different O2
concentrations (16%, 21%, and 26%). Immediately before and immediately after the period of exercise, the inspirate bag was analyzed for NO and CO.
Gas Analyses
NO and CO2 were analyzed by using a rapidly
responding instrument (Logan Research LR 2000, Rochester, UK) that
directs the sample through a rapidly reacting infrared CO2
analyzer to a chemiluminescent NO analyzer with a small (<10 ml)
reaction chamber. The NO analyzer has four separate analysis modes for
quantifying endogenous NO produced 1) through the
nose, 2) during tidal breathing, and 3) during a
maximal single exhalation and, finally, 4) a mode for analyzing inhaled concentrations during therapeutic use of NO. For this
study, the instrument was set in "therapeutic" mode and calibrated
using NO-free compressed air and 4,000 ppb and 80,000 ppb NO
(manufacturer's certificate of analysis; BOC gases, Worsley, Manchester, UK). The CO2 analyzer was calibrated using
O2 (CO2 free), 5% and 6% CO2. To
ensure linearity of these two analyzers, a serial dilution of a mix of
NO and CO2 over the working range was performed. To measure
the response time, a rubber balloon containing 2,660 ppb NO and 2.7%
CO2 was burst by pinprick.
CO was analyzed by using the infrared analyzer of a standard gas
transfer apparatus (Transfertest, PK Morgan, Chatham, Kent, UK).
Linearity was tested by serially diluting a standard CO-He mix of 6%
He and 0.1% CO in air to generate a 25-point plot of CO vs. He.
Blood Analyses
Venous blood was sampled immediately before each experiment and
analyzed within 2 h for Hb, metHb, and COHb using an automated spectrophotometer (IL282, Instrument Laboratories, Cupertino, CA).
Safety Precautions
The exercise laboratory was kept well ventilated at all times.
The stock NO cylinder (1,000 ppm in nitrogen) was kept securely fastened to the purpose-built trolley at all times. The inspired NO
concentration in the Douglas bag was checked before inhalation and was
continuously monitored breath by breath during the experiment.
Calculations
Alveolar NO and CO2.
The NO, CO2, and time (in s) readings were downloaded as
Excel spreadsheet files (Microsoft) from the Logan analyzer using the
"datadump facility." For each individual, four files were created:
mixed exhaled (breathing air on exercise), mixed exhaled (breathing NO
and CO on exercise), inhaled (breathing NO and CO on exercise), and
breath by breath (breathing NO and CO on exercise.) For the inhaled
file, the concentrations were derived as the mean of the column of
readings. For the breath-by-breath files, X-Y plots of NO as a function
of time and CO2 as a function of time were drawn using a
spreadsheet charting program (Works 3.1, Microsoft). The
FACO2 was taken as one-third of the way
along the alveolar plateau (Fig. 1)
(5). For NO, the alveolar phase was identified visually as
a stepwise reduction in the rate of fall of NO concentration with time
(Fig. 2), a line of best fit was drawn,
and the concentration one-third of the way along was taken as
FANO. FECO and
FENO were taken as the mean of the column of
readings from the exhaled bag.
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Fig. 1.
Change in exhaled NO concentration with time over 2 breaths. On the second curve, the method of fitting a straight line to
the estimated NO alveolar plateau is shown. The value of 500 ppb is the
estimated alveolar concentration one-third of the way along the
plateau. For clarity, the figure has been drawn by using the line chart
option of the Microsoft Excel chart wizard to simulate an analog output
from the NO analyzer.
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Fig. 2.
Change in exhaled CO2 concentration with time
over 2 breaths. On the second curve, the method of fitting a straight
line to the estimated alveolar CO2 plateau is shown. The
value of 6.5% is the estimated alveolar concentration one-third of the
way along the plateau. For clarity, the figure has been drawn by using
the line chart option of the Microsoft Excel chart wizard to simulate
an analog output from the CO2 analyzer.
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Dead space calculations.
Anatomic dead space was estimated as 2.2 × weight (kg) + age
in yr (6). CO2 dead space (6) was calculated
from
|
(1)
|
NO dead space was calculated as follows
This rearranges to yield
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(2)
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Diffusing capacity calculations.
We calculated DLCO and
DLNO by using estimated anatomic dead space
[(a) DCO I in Bates et al. (1)] and also
DLCO using CO2 dead space [(e) in
Ref. 1]
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(3)
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Equation 3 was calculated using the predicted
anatomic dead space for both gases and, for CO, the CO2
dead space (Eq. 1).
In addition, for NO, because we had a rapidly reacting NO analyzer, we
adapted Bates et al.'s method using end-tidal concentrations [(c)
DCO II in their paper] for NO and used end-tidal
FENO from the expired NO curve (Fig. 2) as an
estimate of FANO
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(4)
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There were thus two estimates of DLCO
and DLNO per subject.
For dead space and DL calculations, the respiratory
quotient was assumed to be 1 (see RESULTS).
Calculation of Dm and Vc.
Calculations were made as follows
|
(5)
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(6)
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(7)
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For derivation of these equations, see Ref. 4. The
value of NO (5) was taken as 4.5 ml · min1 · Torr1 · ml1
(1,500 mmol · min1 · kPa1 · l1)
and CO (7) calculated from
1/CO = 1.3 × 103 + 4.1 × 103 (PcO2) min · Torr.
PcO2 was taken as 100 Torr. For both CO and NO, correction for Hb was made by multiplying by Hb × (1 COHb metHb)/14.6.
For calculation of DmCO, the assumption (8) is
made that NO is infinity
|
(8)
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and Vc was obtained by inserting this value for DmCO
into Eq. 7.
Statistical Analysis
The paired t-test was used to compare the calculated
NO dead space to the predicted anatomic dead space and to the
CO2 dead space and to compare DLNO
calculated from FANO and predicted anatomical dead space. Values are given as means ± SD.
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RESULTS |
Performance of Analyzers
The NO-CO2 analyzer was linear to serial dilution over
the working range down to NO concentrations below 250 ppb and
CO2 below 0.55% when departure from linearity occurred;
these were well below the alveolar and mixed expired concentrations.
The minimum detectable concentration of NO was 60 ppb and
CO2 0.3% in therapeutic mode. The response time to half
signal after balloon burst was 160 ms for CO2 and 400 ms
for NO; the CO2 column was therefore "cut and pasted"
down by 240 ms in the spreadsheet to synchronize concentration data for
the two gases. A plot of CO and He was linear with intercept zero over
the working CO range.
Subject Data
Table 1 illustrates the nine subjects' physical characteristics.
Measured and Derived Variables
Mean O2 was 1.3 ± 0.2 l/min.
Mean respiratory quotient (RQ) was 0.96 ± 0.06. No loss
of NO or CO occurred from the inspired bag. There was no detectable
(i.e., <60 ppb) background NO in the laboratory atmosphere or in the
exhaled breath sample for any subject with the instrument in the
therapeutic mode. The breath-by-breath X-Y plots of exhaled
concentration and time are shown in Fig. 1 for CO2 and Fig.
2 for NO. The NO plot comprises a peak of inhaled NO, a steep fall
representing dead space, and then a shallower alveolar slope. The mean
inhaled, mean mixed exhaled, and alveolar NO were 5,218 ± 1,675, 1,402 ± 381, and 942 ± 250 ppb, respectively.
The calculated CO2 and NO dead spaces are shown in Table
2. The NO dead space is significantly
different (P < 0.001) from the CO2 dead
space but not from the anatomic dead space. Calculated DLCO and DLNO together
with Dm and Vc are shown in Tables 2 and 3. There are no significant
differences between the two estimates of DLNO.
DLNO appears constant over 30 s of
observation (Fig. 3).
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Fig. 3.
Ratio of steady-state diffusing capacity for NO
(DLNO) to mean DLNO for
the 9 subjects over ~30 s. DLNO was
calculated by using mixed exhaled NO and breath-by-breath alveolar
CO2 concentration.
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DISCUSSION |
Major Findings
Estimates of dead space.
The NO dead space is strikingly similar to the predicted
anatomical dead space but significantly lower, on average about
one-half, than the CO2 dead space. However, the estimate of
NO dead space is less precise because the alveolar slope for NO is
steeper. Clearly, NO uptake is occurring within the alveolar dead
space. NO is a reactive gas particularly in solution, and this reaction could be with groups other than Hb in the lining of unperfused alveoli.
Heller and Schuster (9), however, discounted a chemical reaction of NO with lung tissue during single-breath
DLNO measurements in rabbits because there was
no variation in DLNO either with duration of
breath hold or with FINO. Their results are in
agreement with our single-breath observations of a semilog decline in
FANO with intercept 1 in two human subjects
(4) and identical values of
DLNOSB at
FINO of 0.75 ppm and 60 ppm (Borland C and Cox
Y, unpublished observations). A more plausible explanation is
as follows: the physiological dead space exceeds the anatomic dead
space because some alveoli have a ventilation-perfusion ratio approaching infinity. Such alveoli and their associated capillaries will secrete minimal CO2. On the other hand,
DLNO is diffusion limited, independent of
capillary blood flow, and (if NO approaches infinity)
independent of capillary blood volume. Uptake of NO would therefore
occur even in these alveoli, and the NO dead space would correspond to
the anatomic dead space.
Values for DLNO.
The values for DLNO using the predicted
anatomic dead space and the dead space calculated from
FANO are similar (Table 2). The higher mean
value for DLNO calculated from
FANO is largely due to subject 3,
who had wide between-breath variation in VT and
FANO. The average
DLNOSS of ~200
ml · min1 · Torr1 measured
here on moderate exercise exceeds the single-breath value measured at
rest (125 ml · min1 · Torr1) by ~70
ml · min1 · Torr1
(4). This is at first surprising because steady-state
measurements are made at VT rather than total lung capacity
and DLNOSB is highly lung volume
dependent (4), falling by 45 ml · min1 · Torr1 with a
reduction in VA from 7 to 4 liters. It is to be noted that
it is the volume that the inhaled NO is distributed into rather than
the inhaled volume that is important here. During steady-state
breathing, the NO will be distributed into a volume of functional
residual capacity plus VT, whereas during a single breath
it will be distributed into VA. The difference
between these volumes is perhaps only 1-2 liters. However, we also
noted a rise in DLNOSB
with exercise to 210 ml · min1 · Torr1 at
1-2 l/min O2, so the
overall value could be little changed. These average values therefore
may be used to interpret values for alveolar partial pressure of NO in
models of NO production (10).
Values for DLCO, Dm, and Vc.
The mean DLCOSS on moderate
exercise exceeds DLCOSB measured at
rest by ~5-10
ml · min1 · Torr1. Our
previous mean value for DLCOSB at
1.4 l/min O2 in three individuals was 48 ml · min1 · Torr1, so again
it is possible that the discrepancy is due to exercise. Other workers
have found DLCOSS to be less than
DLCOSB (13).
DmCOSS is close to our previous value for
DmCOSB (316 ml · min1 · Torr1).
However, Vc is about three times as large (56 ml single breath) (3). It is possible to use Eq. 7 to calculate
Vc on exercise from our previous combined single-breath data
(4), and a figure of 101 ml is obtained. In contrast,
DmCOSB is 343 ml · min1 · Torr1. It would
appear that during tidal breathing on exercise Vc is one to two
times that which is measured during apnea at total lung capacity on
exercise. One explanation is that the capillaries are flattened when
the alveoli are fully inflated and stretched. Alternatively, maximal
inspiration recruits alveoli that are normally less well ventilated,
less well perfused, and hence of lower Vc. The increased cardiac output
of exercise dilates capillaries and recruits capillaries, hence
increasing Vc. All these processes have little effect on Dm because it
is probable that NO uptake is largely independent of Vc.
Variation in DLNO between
breaths.
It was not possible to perform a complete breath-by-breath analysis for
DLNOSS. Although we could measure
FANO on a breath-by-breath basis and inhaled NO
would not have varied between breaths, it was not possible to calculate
the mixed exhaled NO on a breath-by-breath basis. To do so would have
needed exhaled flow or volume averaging of the exhaled NO signal, which
is not possible with the analyzer in therapeutic mode. However,
calculating DLNOSS by using
FENO and breath-by-breath
FANO does not show any alteration of
DLNOSS with duration of inhalation or number of breaths (Fig. 3). Despite NO being vasoactive, there appears to be no evidence that breathing it alters the measurement of
DLNOSS.
Critique of Method
As with DLCOSS,
DLNOSS suffers from the inherent
inaccuracy of estimating FANO. We found a steep
alveolar phase for exhaled NO (Fig. 2), and the place on the curve
chosen as a representative value for FANO
inevitably influenced DLNOSS to a
great extent. DLNOSB measurements
are therefore more reproducible (4).
DLNOSS is more practical for exercise measurements, and indeed we studied
DLNOSS on exercise because at rest
DLCOSS is greatly affected by regional inhomogeneity in diffusing capacity, and we anticipated similar problems with DLNOSS. It
would have been of interest to monitor
DLNOSS continuously during
increasing exercise and to have several replicates per subject.
However, this would have involved exposure to 5,000 ppb NO for many
minutes over several days, and we thought that this could be unsafe
given that there is uncertainty regarding the safe exposure
concentrations for NO. This concentration was chosen because it is
stable in air but sufficiently high for interference from endogenous NO
not to be a problem. The steady-state method is more applicable to use
during artificial ventilation in patients and for animal work.
Comparison With Other Work
All three groups who have made DLNO
measurements have applied the classic Roughton and Forster model
(1/DL = 1/Dm +1/Vc) originally derived for CO transfer
to NO transfer, although each group has made different assumptions,
leading to differing values for Dm and Vc. Guenard et al.
(8) assumed that, because the rate of reaction of NO with
Hb is extremely rapid compared with the membrane conductance (Dm),
DLNO approximates to DmNO and is therefore twice DmCO because the ratio of water solubility
to the square root of molecular weight for NO is twice that
for CO. This value for DmCO is entered into the equation.
By their reasoning, DLNO is entirely
independent of capillary blood volume. Using this approach yields lower
figures for Dm and higher values for Vc than we have obtained (see
Table 3). Their method and ours use upper
and lower limits for and give correspondingly lower and upper
limits for Dm and Vc. All the groups have assumed that NO is independent of alveolar
PO2, although there is no in vitro evidence for
this given the technical difficulties due to the rapid reaction of NO
and O2. However, our laboratory (3) has previously found some O2 variability of
DLNO over the physiological PO2 range and presumed this to be due to
alteration in Dm or Vc.
Values for
DLNO-to-DLCO
ratio and the reaction resistance.
The ratio of DLNO to
DLCO varies between 3.9 and 4.8, depending on which estimates of DL are used. These
estimates are rather lower than those made using single-breath
estimates (4, 7), perhaps because of the exercise-induced
increase in DLCO.
Schuster and Heller (9) extended Guenard's
formula and obtained the reaction resistance/total transfer
resistance = DLCO/COVc = 1-2/(DLNO/DLCO).
With the use of Heller and Schuster's formula (9), which
assumes that NO is infinity, the reaction resistance to
CO uptake from our data of
1-2/(DLNO/DLCO)
gives a figure of 0.48, which is close to their estimate (0.4).
However, if the reaction resistance is calculated as
DLCO/(CO × Vc) using our value
for Vc (Table 3) and using the O2-dependent term for
CO (see calculation of Dm and Vc above), then a figure
of 45.6/(158 × 4.1 × 103 × 100) = 0.7 is obtained. It is clearly crucial to know the in vivo value of
NO to correctly calculate the reaction resistance to CO uptake.
Directions for Further Work
It would be important to confirm our observations by
making measurements at rest, increasing levels of exercise and varying PO2. A simultaneous rapidly responding flow or
volume channel would allow breath-by-breath measurement and also the
study of within-breath variation of DLNO with
VA. The interpretation of DLNO and
indeed DLCO crucially depends on how values for
obtained in the laboratory relate to the situation in the pulmonary
capillary. One approach would be to measure
DLNO and DLCO
simultaneously while varying the hematocrit. If 1/DL is
plotted as a function of 1/Hb for both gases, then the ratio of slopes
is NO/CO. These experiments would be best
performed in an isolated lung preparation. Studies of
DLNO/DLCO in anemia in
humans have given conflicting results, no doubt because chronic anemia
affects other aspects of gas transfer than hematocrit (2).
In an isolated lung model, it should be possible to keep these factors constant.
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APPENDIX |
Worked Example Using Data for Subject 1
Subject 1 was 45 yr old and weighed 80 kg.
The experiment was performed on a day when the laboratory
temperature was 24°C and PB was 752 Torr. Saturated vapor
pressure at 37°C was assumed to be 47 Torr.
VT = 2,200 ml, RR = 20.3, FECO2 = 4.8%,
FACO2 = 5.7%,
FICO = 0.106%,
FECO = 0.067%,
FINO = 5,260 ppb,
FENO = 1,467 ppb,
FANO = 1,200 ppb, Hb = 15.3 g/dl,
COHb = 1%, metHb = 0.3%.
Dead space calculations.
Anatomical dead space was estimated as 2.2 × [weight (kg) + age (yr)] (6)
CO2 dead space (6) was calculated from
|
(A1)
|
NO dead space was calculated from
|
(A2)
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Diffusing capacity calculation for
DLCO.
Using predicted anatomic dead space (a DCO 1 in Bates et
al.)
|
(A3)
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Using CO2 dead space [(e) in Bates et
al.]
Diffusing capacity calculation for
DLNO.
Using the predicted anatomic dead space for NO
Using end-tidal FENO from the expired NO
curve (Fig. 2) as an estimate of
FANO
![D<SC>l</SC><SUB>NO</SUB><IT>=</IT>V<SC>t</SC><IT>×</IT>RR<IT>×</IT>(F<SC>i</SC><SUB>NO</SUB><IT>−</IT>F<SC>e</SC><SUB>NO</SUB>)<IT>/</IT>[F<SC>a</SC><IT>×</IT>(P<SC>b</SC><IT>−47</IT>)]<IT>=2,200×20.3×273/</IT>(<IT>273+24</IT>)<IT>×</IT>(<IT>5,260−1,467</IT>)](/content/vol90/issue2/fulltext/538/img022.gif)
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(A4)
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For dead space and DL calculations, the respiratory
quotient was assumed to be 1 (see RESULTS).
Calculation of Dm and Vc.
Calculations were made as follows
|
(A5)
|
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(A6)
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(A7)
|
For derivation of these equations, see Ref. 3. The
value of NO (5) was taken as 4.5 ml · min1 · Torr1 · ml1
(1,500 mmol · min1 · kPa1 · l1)
and CO (7) calculated from
1/CO = 1.3 × 103 + 4.1 × 103 (PcO2)
min · Torr/ml1.
PcO2 was taken as 100 Torr. For both CO and NO, correction for Hb was made
by multiplying by Hb × (1 COHb metHb)/14.6.
For subject 1, we used the estimate of
DLCO using the CO2 dead space and
DLNO using end-tidal NO as an estimate of
alveolar NO
For calculation of DmCO, the assumption
(8) is made that NO is infinity
and Vc was obtained by inserting this value for
DmCO into Eq. 7
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FOOTNOTES |
Address for reprint requests and other correspondence: C. Borland, Dept. of Medicine, Hinchingbrooke Hospital, Huntingdon, Cambs.
PE18 8NT, UK (E-mail:
colin.borland{at}hbhc-tr.anglox.nhs.uk).
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. Section 1734 solely to indicate this fact.
Received 12 April 2000; accepted in final form 5 September 2000.
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REFERENCES |
1.
Bates, DV,
Boucot NG,
and
Dormer AE.
The pulmonary diffusing capacity in normal subjects.
J Physiol (Lond)
129:
237-252,
1955.
2.
Borland, C.
NO and CO transfer.
Eur Respir J
3:
977-978,
1990[Web of Science][Medline].
3.
Borland, CDR,
and
Cox Y.
Effect of varying alveolar oxygen partial pressure on diffusing capacity for nitric oxide and carbon monoxide, membrane diffusing capacity and lung capillary blood volume.
Clin Sci (Colch)
81:
759-765,
1991[Medline].
4.
Borland, CDR,
and
Higenbottam TW.
A simultaneous single breath measurement of pulmonary diffusing capacity with nitric oxide and carbon monoxide.
Eur Respir J
2:
56-63,
1989[Abstract].
5.
Carlsen, E,
and
Comroe JH.
The rate of uptake of carbon monoxide and of nitric oxide by normal human erythrocytes and experimentally produced spherocytes.
J Gen Physiol
42:
83-107,
1958[Abstract/Free Full Text].
6.
Cotes, JE.
Lung Function: Assessment and Application in Medicine. Oxford, UK: Blackwell Scientific, 1993, p. 297, 301-311.
7.
Forster, RE.
Diffusion of gases across the alveolar membrane.
In: Handbook of Physiology. The Respiratory System. Gas Exchange. Bethesda, MD: Am. Physiol. Soc, 1987, sect. 3, vol. IV, chapt. 5, p. 71-88.
8.
Guenard, H,
Varene N,
and
Vaida P.
Determination of lung capillary blood volume and membrane diffusing capacity in man by the measurements of NO and CO transfer.
Respir Physiol
70:
113-120,
1987[Web of Science][Medline].
9.
Heller, H,
and
Schuster KD.
Role of reaction resistance in limiting carbon monoxide uptake in rabbit lungs.
J Appl Physiol
84:
2066-2069,
1998[Abstract/Free Full Text].
10.
Hyde, RW,
Geigel EJ,
Olsszowska AJ,
Krasney JA,
Forster RE, II,
Utell MJ,
and
Frampton MW.
Determination of production of nitric oxide by lower airways of humans: theory.
J Appl Physiol
82:
1290-1296,
1997[Abstract/Free Full Text].
11.
Lundberg, JON,
Weitzberg E,
Lundberg JM,
and
Alving K.
Nitric oxide in exhaled air.
Eur Respir J
9:
2671-2680,
1996[Abstract].
12.
Mercer, RR.
Morphometric analysis of alveolar responses of F344 rats to subchronic inhalation of nitric oxide.
Res Rep Health Eff Inst
88:
1-15,
1999.
13.
Sackner, MA,
Raskin MM,
Julien PJ,
and
Avery WG.
Effect of lung volume on steady-state pulmonary membrane diffusing capacity and pulmonary capillary blood volume.
Am Rev Respir Dis
104:
408-417,
1971[Medline].
J APPL PHYSIOL 90(2):538-544
8750-7587/01 $5.00
Copyright © 2001 the American Physiological Society
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ABSTRACT
INTRODUCTION
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