Vol. 94, Issue 1, 75-82, January 2003
Tidal volume single-breath washin of SF6 and
CH4 in transient microgravity
Brigitte
Dutrieue1,
Manuel
Paiva1,
Sylvia
Verbanck2,
Marine
Le Gouic3,
Chantal
Darquenne4, and
G. Kim
Prisk4
1 Biomedical Physics Laboratory, Université
Libre de Bruxelles, 1070; 2 Department of Pneumology,
Akademisch Ziekenhuis, Vrije Universiteit Brussels, 1090 Brussels,
Belgium; 3 European Space Agency, ESTEC,
NL-2200 AG Noordwijk, Holland; and
4 Department of Medicine, University of California,
San Diego, La Jolla, California 92093-0931
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ABSTRACT |
We performed tidal volume
single-breath washins (SBW) by using tracers of different diffusivity
and varied the time spent in microgravity (µG) before the start of
the tests to look for time-dependent effects. SF6 and
CH4 phase III slopes decreased by 35 and 26%,
respectively, in µG compared with 1 G (P < 0.05), and the slope difference between gases disappeared. There was no
effect of time in µG, suggesting that neither the hypergravity period
preceding µG nor the time spent in µG affected gas mixing at
volumes near functional residual capacity. In previous studies using
SF6 and He (Lauzon A-M, Prisk GK, Elliott AR, Verbanck S, Paiva M, and West JB. J Appl Physiol 82: 859-865,
1997), the vital capacity SBW showed an increase in slope difference
between gases in transient µG, the opposite of the decrease in
sustained µG. In contrast, tidal volume SBW showed a decrease in
slope difference in both µG conditions. Because it is only the
behavior of the more diffusive gas that differed between maneuvers and
µG conditions, we speculate that, in the previous vital capacity SBW,
the hypergravity period preceding the test in transient µG provoked
conformational changes at low lung volumes near the acinar entrance.
vital capacity single-breath washout; phase III slope; helium; gas
mixing; sustained microgravity
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INTRODUCTION |
THE PHASE III
SLOPE of the N2 single-breath washout is an
index of inhomogeneities of ventilation in the lung
(8). These inhomogeneities are generated by
convective processes, which can be gravitationally or
nongravitationally dependent, and by interaction between diffusion and
convection (12). Addition of tracer gases of different
diffusivity (usually He and SF6) to the test gas mixture,
i.e., a He and SF6 single-breath washin (SBW), allows investigation of the diffusion-convection-dependent ventilation processes that occur at different levels in the lung periphery (7, 9). In adult humans, the He phase III slope is
generally considered an index of inhomogeneity of gas mixing occurring
around the acinar entrance, whereas the SF6 phase III slope
characterizes gas mixing more peripherally inside the acinus (19,
11, 5). Any changes in the SF6-He slope difference
are assumed to be caused in the lung periphery since purely convective
processes will produce the same contributions to He and SF6
phase III slopes.
The vital capacity single breath washout (VC-SBW) test using He and
SF6 has been performed in sustained microgravity (µG; 9 days) during spaceflight (18) and showed decreased He and SF6 slopes that could be partially attributed to the
elimination of the gravity-dependent convective component of the
gas-mixing process. Importantly, however, the SF6-He slope
difference virtually disappeared, principally because of a smaller
decrease in the phase III slope for He than for SF6 on
going from 1 G to µG. This suggested a change in gas mixing in the
lung periphery as a result of the removal of gravity in addition to the
more central changes that affect convective mixing. A subsequent VC-SBW
study in transient µG (20-25 s) during parabolic flight
(10), aimed at elucidating the mechanisms involved, showed
a similar SF6 slope decrease as in sustained µG
conditions, whereas the reduction in He slope was much greater in
transient µG compared with sustained µG. As a consequence, the
SF6-He slope difference of the VC-SBW was actually increased in transient µG, the reverse of what was observed in sustained µG. The difference in the behavior in VC-SBW performed in
transient and sustained µG could possibly be explained on the basis
of 1) the potential effects of the preceding period of
hypergravity on measurements performed in transient µG and
2) a change in acinar conformation in sustained µG that
occurs with a time constant well in excess of the 25 s of µG
available in parabolic flight.
Further adding to the knowledge of changes in acinar gas mixing are the
results of bolus inhalation studies performed during VC maneuvers in 1 G and during transient µG. Those studies showed that there was an
effect of airway closure at low lung volumes on VC-SBW phase III slope
(4).
When SBW tests were performed in sustained µG at lung volumes near
functional residual capacity (FRC; thus eliminating the effect of
airway closure), these tidal volume (VT)-SBW showed phase
III slope decreases for both gases with the SF6-He slope difference also significantly reduced from 1 G to µG (similar to that
seen in VC-SBW in sustained µG). In all of these studies, the
decreases in SF6 slope from 1 G to µG were similar,
irrespective of the SBW maneuver or of µG duration. In contrast, the
He phase III slope behavior was different in VC-SBW in transient µG,
which suggests a physiological phenomenon that occurs around the
entrance of the acinus or between neighboring acini (10)
and is likely associated with airway closure. On the basis of these
preceding studies, and in particular the discordant He slope behavior
in VC-SBW performed in sustained µG vs. transient µG, we were
desirous of testing two alternative hypotheses. First was the
hypothesis that there is a short time dependence in the conformational
change induced by µG at the level of the acinar entrance. If this is the case, then VT-SBW performed in transient µG would be
expected to be largely similar to VC-SBW performed in transient µG
(an increased SF6-He slope difference), and this slope
difference might be expected to change with time spent in µG before
beginning of the test. Second was the hypothesis that gas mixing in all lung volume ranges is not equally affected by the removal of gravity, especially lung volumes that are below closing capacity
(4). If this is the case, then VT-SBW
performed in transient µG would be expected to be largely similar to
VT-SBW performed in sustained µG and would show a
decrease in the SF6-He slope difference.
In the absence of any VT-SBW data obtained under transient
µG conditions, it was not possible to determine the validity of either of these hypotheses. Hence, we performed a study of
VT-SBW in transient µG (parabolic flight) by using
CH4 and SF6 as tracers of different diffusivity
(CH4 was used as a surrogate for He). In these tests, we
varied the time interval the subject had been in µG after the
hypergravity period before the onset of the VT-SBW maneuver
to look for time-dependent effects with a short time constant.
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METHODS |
Experimental system.
The system used was a prototype of that developed for spaceflight
(ARMS, Innovision, Odense, Denmark). Briefly, it was comprised of a
differential pressure flowmeter connected to the mouthpiece, which in
turn was connected to a computer-controlled rotary valve to direct the
breathing path. The subject was responsible for actuation of the valve
at predetermined points in the test maneuver. Gas was sampled from the
mouthpiece by a photoacoustic gas analyzer with a response time
(10-90%) of ~250 ms. Data were acquired by an IBM Thinkpad
(model 760-ED) at 33 Hz for the gas signals and 200 Hz for the flow
signal. The software provided prompts and feedback to the subject to
control flow rate when required.
The gas analyzer was calibrated before each test session by sampling
gas from calibration gas cylinders. Gas analyzer transit time was
determined by measuring the time required for a sharp puff containing
CO2 to be detected by the gas analyzer, and the data were
then aligned accordingly. This maneuver was repeated daily, and average
values were 0.935 ± 0.015 s. Delays in gas analyzer response time
between the different gas species were measured from gas calibration
tests. The delays were slightly different but constant relative to
CO2 to within 0.03 s. The dynamic response time of the
gas analyzer (~0.250 ms) is rapid compared with the relatively slowly
changing gas concentration signal that occurs over phase III of the
expiration, and thus the slope measurement is minimally affected by the
gas analyzer dynamics. The flowmeter was calibrated by integration of
the flow strokes of a 3-liter calibration syringe (model 5530, Hans
Rudolf). Flow drift was checked by measuring 2 s of imposed zero
flow condition (flowmeter occluded) before each maneuver, and flow was
corrected accordingly.
Data were collected in an A300 zero-G aircraft (Novespace Centre
National d'Etudes Spatiales, CNES). A typical flight consisted of a
climb to an altitude of ~6,000 m with the cabin pressurized to ~600
Torr. The aircraft was pitched up at 1.8 vertical acceleration (Gz) to a 50° nose-high attitude; this hypergravity phase
lasted ~20 s. Then the nose was lowered to abolish wing lift, and
thrust was reduced to balance drag (thus maintaining µG). A ballistic flight profile resulted and was maintained until the nose of the aircraft was 40° below the horizon. In this manner, µG was
maintained for ~22 s. A 1.8 Gz pullout of ~20 s
followed the µG phase until the aircraft returned to the horizontal,
which was followed by 1-G flight conditions for at least 90 s. The
cycle was repeated for 31 successive parabolas.
Subject and data collection.
Eleven healthy subjects, who were nonsmokers for at least 5 yr before
the start of data collection, participated in the study. They had
undergone medical examinations equivalent to Federal Aviation
Administration class II and reported no pulmonary problems on
questioning. They were well trained in these respiratory maneuvers, and
only tests meeting predefined quality control criteria (see Test
maneuver) were retained; therefore, results come from nine of the
subjects (5 women and 4 men) aged 32.3 ± 6.1 yr, weight 63.7 ± 14.4 kg, and height 170 ± 10 cm (means ± SD). All
subjects took antimotion sickness drugs (0.4 mg scopolamine, 5 mg
dexedrine) ~1 h before flight. The data were collected with the
subjects sitting in a standard aircraft seat and restrained with a lap belt both during 1-G and µG phases of the parabolic flights. All preflight data were collected on the ground under sea level conditions. The µG data were collected at a pressure of ~600 Torr. All
experiments were reviewed and approved by the ESA Medical Board, and
all subjects were fully informed and provided written consent.
Test maneuver.
The maneuver as shown in Fig. 1 began
with quiet breathing through the mouthpiece. On command, the subject
relaxed to FRC and the rotary valve turned, connecting the subject to
the bag containing the test gas. It was composed of 1.0%
SF6, 2.4% CH4, 25.0% O2, balance
N2; SF6 and CH4 were able to be
analyzed by the photoacoustic gas analyzer. Subject inspired a preset
volume (typically 1.37 liters; see Table
1) of test gas at a controlled flow rate
of ~0.4 l/s (Table 1). At the end of inspiration, the subject performed a short breath hold (BH; ~2 s; Table 1) that allowed the valve to be actuated before expiration. Expiration was
performed at the same controlled flow rate until the subject reached
residual volume (RV). On the aircraft, the start of the inspiration was
performed at the beginning of the µG phase or after a time
(
tµG) of 5 or 10 s of µG (see Fig.
1). All subjects performed the test at least twice in each of the four
conditions (1 G and µG for tµG = 0, 5, or 10 s).
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Fig. 1.
Respiratory maneuver during a parabola. After a
predetermined time in microgravity (tµG),
the subject inspired ~1.4 liters from functional residual capacity
(FRC), performed a short breath hold (BH), and then expired to residual
volume before the end of the microgravity (µG) phase. Vertical dotted
lines marked the beginning of the µG phase and the start of the test.
1.8 Gz, hypergravity.
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Data analysis.
Data were first corrected for gas analyzer transit time, and volume was
obtained from flow integration corrected for zero offset. Tests were
then selected according to the following inclusion criteria:
1) mean inspiratory and expiratory flow rate had to be in a
consistent window of ±0.15 l/s around the mean for that subject,
2) inspired volume had to be between 1 and 1.6 liters, 3) BH between inspiration and expiration had to be in a
consistent window of ±0.5 s around the mean for that subject, and
4) tests performed in the aircraft had to be completed
during the µG phase. Inspired volume, flow, and BH resulting after
test selection are presented for 1-G and µG conditions in Table 1.
SF6 and CH4 were analyzed by considering the
pretest gas concentration in the lung as 0% and the inspired gas
concentration as 100%, which resulted in positive phase III slopes.
For each test, gas concentration was plotted against expired volume and the phase III slope was computed from linear regression between 0.7 and
1.2 liters of expired volume. Finally, the slope was divided by the
concentration at 1.2 liters of expired volume. The volume limits used
for the slope regression in combination with the normalization leads to
test results exactly comparable to that of the first breath of the
multiple-breath washout data from spaceflight (17). Expiratory reserve volume (ERV) was computed as the difference between
expired and inspired volume.
Statistical analysis was performed by using Statistica (Statsoft,
Tulsa, OK) and Microsoft Excel (Microsoft, Redmond, WA). Comparisons
involved one- and two-way ANOVA tests with Tukey's post hoc testing.
Values are means ± SE, and significant differences were accepted
at P < 0.05.
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RESULTS |
Phase III slope vs. time in µG.
Normalized phase III slopes are presented in each gravity condition (1 G and tµG = 0, 5, 10 s) in Fig.
2. Figure 2,
A and B, shows results for each subject for
SF6 and CH4, respectively. Each point
represents the mean value of all tests meeting the acceptance criteria
by a given subject in a given gravity condition. The complete set of
data is presented in Table 2 and shows
the between-test variability. Figure 2C shows the
SF6 and CH4 slopes obtained when pooling all
subjects together. Phase III slope fell from 1 G to µG for all
tµG. On the basis of the one-way ANOVA test, no significant differences (P > 0.2) were found
between slopes obtained at different tµG
conditions for both gases. The two-way ANOVA test revealed no
significant difference (P > 0.9) between
SF6 and CH4 for each
tµG condition.
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Fig. 2.
Normalized phase III slope from tidal volume
single-breath washout (VT-SBW) in 1 G and after different
tµG in µG. SF6 (A)
and CH4 (B) show individual data: each point
represents the mean value of all tests of 1 subject performed in the
specified condition (1 G or µG with
tµG = 0, 5, or 10 s).
C: same results for all subjects pooled together. Values are
means ± SE. #Significantly different compared with 1-G value
(P < 0.05).
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ERV did not change significantly between different
tµG conditions (P > 0.5, from one-way ANOVA test). Because no significant differences were found
between the different tµG conditions for
SF6, CH4, and ERV, µG data were pooled for
further analysis. As presented in Table 1, although there was some
variability in flow rate and BH time between subjects, subjects were
generally consistent in their performance of the tests between 1 G and µG, except for ERV, which decreased significantly
(P < 0.005) from 1 G to µG.
Comparison of phase III slopes between respiratory maneuvers and
gravity conditions.
Figure 3D presents, for both
gases, the normalized phase III slope obtained in 1 G compared with
µG with data from all different tµG
pooled together. From a two-way ANOVA test, µG slopes were
significantly smaller (P < 0.05) than the 1-G slopes
for both gases. SF6 and CH4 slopes were
significantly different (P < 0.001) in 1 G, whereas
the significance disappeared in µG (P > 0.5), which
meant that the SF6-CH4 slope difference was
reduced in µG compared with 1 G.
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Fig. 3.
Comparison between 1-G and µG data obtained in different µG
conditions and from different test maneuvers. A: vital
capacity single-breath washout (VC-SBW) phase III slopes obtained in 1 G standing position and in sustained µG during spaceflight mission
(data from Ref. 18). B: VC-SBW phase III slopes
obtained in 1 G sitting position and in transient µG during parabolic
flight (data from Ref. 10). Both vital capacity phase III
slopes were normalized to 100% background and 0% inspired gas, giving
slope in %/liter. C: tidal volume phase III slope
(VT-SBW) obtained in 1 G standing position and in sustained
µG during spaceflight (data from Ref. 17). D:
VT-SBW phase III slope with all subjects and all µG data
pooled together (data from present study) obtained in 1 G sitting
position and in µG during parabolic flight. Both tidal volume phase
III slopes were normalized by the end-expiratory concentration and then
expressed in liter 1 (see text for details). Note the
difference in units between VC-SBW and VT-SBW.
 , SF6;  , CH4;
 , He. Values are means ± SE. * Significant
difference between slopes of different gas diffusivities
(P < 0.05).
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For the purposes of comparison, the data obtained for VC-SBW during
sustained µG (spaceflight) (18) and during transient µG (parabolic flight) (10) as well as VT-SBW
slope obtained from the first breath of multiple-breath washout
performed in sustained µG (17), each with their 1-G
control data, are presented in Fig. 3, A-C,
respectively. It should be noted that, in the VC-SBW tests, the units
of phase III slopes were % per liter, whereas in the
VT-SBW test, the units were
liters1. The data in Fig. 3,
A-C, were performed by using He and SF6. It
is important to note that, in those experiments, the 1-G data compared
with the µG data were significantly different in all cases
(P < 0.05) and that the He and SF6 slopes
were significantly different (P < 0.05) in all
situations except for VC-SBW slope obtained in sustained µG. Both
sustained µG studies were performed by the same subjects (17,
18), and one of these subjects also performed the VC-SBW in
transient µG (10). Results from this particular subject
were representative of the mean tendency in each study, which
highlights the consistency of the three studies. There was no common
subject between the present study and the previous studies.
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DISCUSSION |
The main goal of this study was to shed light on the paradoxical
results obtained for VC-SBW in transient and sustained µG. Compared
with 1-G data, the SF6-He slope difference was decreased in
sustained µG (Fig. 3A) and increased in transient µG
(Fig. 3B). These results could possibly be explained by the
potential effects of the period of hypergravity preceding the
measurements in transient µG and/or by a change in acinar
conformation in sustained µG that occurs with a time constant longer
than the 25 s of µG available in parabolic flights. To determine
the potential effect of time spent in µG, we performed
VT-SBW in parabolic flight and varied the time at which the
test was started during the µG period. It was not possible to vary
the time in µG with a VC-SBW maneuver because this type of maneuver
requires the whole µG period to be completed.
VT-SBW phase III slope: effect of time spent in µG.
The main result of this portion of the study is illustrated in Fig.
2C and shows that there is an abrupt decrease in phase III
slope immediately on transition from 1 G to µG with no subsequent effect of tµG on either CH4 or
SF6 slope, or on their slope difference. Figure 2,
A and B, and Table 2 show that there was considerable consistency between subjects in the response to µG. This
result implies that the hypergravity period preceding µG in parabolic
flight either does not induce conformational change in lung volumes
near FRC or, if it does, the effect persists for >10 s. However, the
similarity between the results obtained in transient and sustained µG
for VT-SBW, i.e., a decrease in phase III slope difference
from 1 G to µG (Fig. 3, C and D), suggests that
the latter explanation is unlikely. Therefore, it appears that
conformational changes affecting the phase III slope of
VT-SBW are only a consequence of µG and happen
immediately after the removal of gravity without subsequent time dependence.
Comparison between VC-SBW and VT-SBW in sustained vs.
transient µG.
The central issue of this portion of the study is illustrated in Fig.
3, which presents a summary of the results obtained for VC and
VT-SBW in transient and sustained µG conditions. The main
differences between transient and sustained µG conditions are that
the µG phase obtained during parabolic flight lasts only 22-25 s
and that it is preceded by a hypergravity phase (1.8 Gz), whereas sustained µG lasts for several days. In the case of VC-SBW, during the sustained µG of spaceflight, the entire maneuver is performed in µG, whereas the short period of transient µG requires that the expiration to RV preceding the test occurs during the hypergravity phase. In contrast to VC-SBW, VT-SBW requires
less time, and it is possible to perform the entire maneuver within the
µG phase available during parabolic flight.
The following four observations can be made from Fig. 3. First, phase
III slope decreased from 1 G to µG for all gases in both VC and
VT-SBW maneuvers, whatever the µG condition
(A-D). This slope reduction can be partially attributed
to the elimination of the gravity-dependent convective component of the
gas-mixing process that affects all gases to the same extent. Second,
the decrease in SF6 slope from 1 G to µG is similar in
all situations (A-D). This suggests that the effect of
µG on the acinar periphery is similar at all lung volume ranges and
in both µG conditions. Third, in A, C, and
D, the slope difference between gas of low (SF6)
and high (He and CH4) diffusivity decreased from 1 G to µG. In particular, results obtained for VT-SBW in both
µG conditions (C and D) are similar, especially
when one considers that CH4 was used instead of He (see
below). Indeed, the slope difference showed a small reduction in
transient µG with respect to 1 G (D), as was previously
observed in sustained µG vs. 1 G (C). This implies that,
irrespective of the time spent in µG, gas mixing at lung volumes near
FRC is similar in both µG conditions. And fourth, in contrast to the
behavior observed in A, C, and D, the
VC-SBW performed in transient µG (B) show an increase of
the slope difference from 1 G to µG. This difference results from a
larger decrease of the He slope for VC-SBW in transient µG compared
with its decrease in other conditions, whereas the SF6
slope reductions are similar in all conditions. The clearly opposite
behavior in slope difference points out that, in the VC-SBW,
1) the main slope alterations from 1 G to transient µG are
induced by conformational changes around the acinar entrance (larger He
than SF6 slope reduction) and 2) they are
generated to a large extent at low lung volume ranges, i.e., at volumes
below closing capacity (where airway closure occurs). This last
observation is in good agreement with previous observations suggesting
that extreme lung volumes and particularly volumes below closing
capacity are the major contributor to gas mixing inhomogeneities in VC
maneuvers and are the most affected by the removal of gravity
(4). This is also supported by the similarity between
VT-SBW in sustained and transient µG, which involves only
lung volumes near FRC.
In the case of the VC-SBW in transient µG, the expiration to RV
preceding the test occurs during the hypergravity phase. As a
consequence, at the beginning of the test, the lung is in a hypergravity configuration. This could possibly explain the difference observed in VC-SBW between µG conditions based on the fact that airway closure is known to be gravity dependent (6) and
has been shown to alter the phase III slope (4).
Furthermore, the greater impact on the He slope compared with the SF6
slope suggests that the airway closure conformational changes occur
mainly in the region of He mixing, i.e., around the acinar entrance.
Gas diffusivity.
In the present study, CH4 was used in the test gas instead
of He as in the previous studies (10, 17, 18) because the gas analyzer available to us in the ARMS system cannot measure He. The
diffusion coefficient of SF6, CH4, and He is
0.1, 0.4, and 0.6 cm2/s, respectively. Previous studies
have shown that He slope reflects inhomogeneity of concentration
generated at the entrance of the acinus, whereas SF6 slope
reflects inhomogeneity occurring at the acinus periphery.
CH4, with its intermediate diffusion coefficient value,
gives information on gas mixing from a position more distal than the
acinar entrance.
Figure 4 shows the simulated
concentration profile (diffusion front) inside the acinus structure at
the end of inspiration, i.e., the mean concentration per generation.
Those simulations were performed with the model presented in Ref.
5, in which the maneuver of the present experiments was
simulated. The position of the steepest part of the diffusion front
corresponds to the point where diffusion and convection are of the same
order of magnitude. It is at this level that the concentration
inhomogeneities are generated by the interaction of diffusion and
convection. These inhomogeneities are reflected in the phase III slope.
On the basis of this mechanism and the diffusion coefficient values, CH4 would be expected to have a slope intermediate between
SF6 and He slopes. The proximity of He and CH4
diffusion fronts with respect to the more peripheral SF6
front (Fig. 4) suggests that phase III slope values for CH4
would be expected to be closer to He than to SF6. In fact,
the model predicts that the SF6-CH4 slope
difference would be ~19% smaller than the SF6-He slope
difference. Despite being obtained on different subjects, the
experimental 1-G data in Fig. 3, C and D, are
consistent with the model. On the basis of the above theoretical and
experimental arguments, we can safely state that CH4 is a
good surrogate for He.
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Fig. 4.
Gas concentration inside the acinus structure at the end
of inspiration. SF6, CH4, and He were
normalized by considering the pretest gas concentration in the lung as
0% and the inspired gas concentration as 100%. Vertical dashed line,
acinar entrance. Curves were simulated with the model described in Ref.
5.
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In the case of the SF6 and CH4 transient µG
data (Fig. 2C), the slope difference was of the same order
of magnitude as the individual slope variability, resulting in a loss
of significance between the slopes of the different gases (Fig.
3D). However, the opposite sign of the change in
SF6-He slope difference from 1 G to µG observed in VC-SBW
compared with the change in SF6-CH4 in
VT-SBW results eliminates concerns that the use of
CH4 instead of He in the present data set may have reduced
the sensitivity of the measurement to such a degree as to hide µG effects.
Another effect on gas diffusivity in the transient µG study is the
lower cabin pressure in the aircraft during parabolic flight than in
studies performed in 1 G on the ground. The diffusion coefficient is
inversely proportional to the pressure. In the present study, the
pressure reduction in µG compared with 1 G increased the diffusion
coefficient by ~21% and consequently moved the diffusion front
approximately one-third of a generation toward the acinar entrance. The
model predicts that such change should decrease the phase III slope by
~10% (5), but because this pressure effect applies to
both gases, the likely impact on our results is small.
ERV and BH.
Because RV has been shown to not change from 1 G to transient µG
during parabolic flight (4), ERV is an indirect
measurement of the FRC in both gravity conditions. Therefore, the
decrease of the ERV observed from 1G to µG (Table 1) reflects a
decrease in FRC of 0.45 ± 0.32 liters, consistent with the
0.41 ± 0.07 liter reduction found in a previous study
(13). The present VT-SBW experiment differs
then from the VT-SBW performed in sustained µG in two
aspects: 1) FRC decreased from 1 G to transient µG, whereas it was kept constant in the sustained µG data set; and 2) a short BH was performed between inspiration and
expiration (both in 1 G and in transient µG). A decrease in FRC was
shown to result either in an increase (15, 16) or a
decrease (1) of the phase III slope. In fact, Crawford et
al. (1) have shown that a decrease in FRC (of ~0.5
liter) has the opposite influence on the phase III slope, depending on
whether the limits for phase III regression are chosen between 0.75 and
1 liter or between 1 and 1.6 liters of expired volume. Considering the
expired volume limits used in the present study (0.7-1.2 liters)
and the variability of FRC decrease between subjects, the observed FRC
decrease probably has no significant impact on the mean phase III
slope. BH has been shown to decrease the phase III slope (2,
16), but in the present study an equivalent BH was performed in
both the 1-G and µG condition, allowing, from the BH point of view,
for direct comparison between 1 G and transient µG. In addition, the
effect of BH is to reduce the intra-acinar concentration inhomogeneity generated during inspiration, and it has been shown to reduce the
influence of other breathing parameters, such as preinspiratory lung
volume (14, 16). Hence, the combined effect of the
end-inspiratory BH and the observed FRC changes on the phase III slopes
is expected to be minor and not likely to affect the results in such a
way as to preclude their interpretation.
Antimotion sickness drugs and other constraints.
The antimotion sickness drug taken by the subjects was composed of 5 mg
of dexedrine and 0.4 mg of scopolamine. To our knowledge, there is no
report of any effect of dexedrine on the airway function. Scopolamine
is of the same family as atropine, which was studied by
Crawford et al. (3). In their study, they found that
atropine increased the degree of ventilation inhomogeneity. However, in the present study, given the lower dose used [0.4 mg compared with 2.0 mg in Crawford et al. study (3)], the larger amount of
time between the medication administration and the test (>1 h compared
with 10 min), and the less direct administration method (oral dose
compared with intravenous), we consider the likely effect to be very
small. Furthering this argument in the VC-SBW transient µG study,
most of the subjects (6 of 8) had taken the same drugs, and the results
of all subjects were similar, i.e., an increase of the
SF6-He slope difference in the transition from 1 G to µG.
In the present study, all subjects took the medication, and the effect
on the slope difference was the opposite (a decrease of the
SF6-He slope difference), which adds to the argument that there was likely little effect of the medication on the airway function.
The study was limited by experimental constraints: a limited number of
parabolas, i.e., µG periods, in a limited number of flights, which
precluded our subjects from performing additional VC-SBW in µG to
verify the comparability with the previous VC-SBW study in transient
µG. Indeed, to obtain a sufficient number of repeat measurements in a
sufficient number of subjects, it was not possible to repeat any
measurement made in previous studies. However, the similarity of the
SF6 results for the same VT-SBW maneuver
performed in different µG conditions (Fig. 3, C and
D) combined with the consistent results for a common subject
in the previous studies (Fig. 3, A-C) produce a
considerable degree of confidence in our results.
In summary, the time spent in µG does not affect gas mixing at lung
volumes near FRC, which implies that conformational changes due to the
removal of gravity occurred virtually immediately at those lung
volumes. There was a totally different behavior between VC-SBW in
transient µG (in which slope difference increased) and VC-SBW in
sustained µG, and VT-SBW in either µG condition (in which slope difference decreased). This suggests that a change in gas
mixing below closing capacity, likely in airway closure configuration,
is the primary mechanism of the observed differences in peripheral gas
mixing between transient and sustained µG seen previously
(10).
| |
ACKNOWLEDGEMENTS |
The authors thank André Kuipers, Dag Linnarson, and Alain Van
Muylem for contributions to achieve those experiments and for statistical analysis help. We also acknowledge the team of the A300-Zero G of the Novespace/CNES for organization of the parabolic flights and Innovision for building the ARMS system.
| |
FOOTNOTES |
This work was supported by National Aeronautics and Space
Administration (NASA) Subcontract G860600J67 and European Space Agency
(ESA) funding for parabolic flight campaign. M. Paiva was supported by
contract Prodex with the Belgian Federal Office for Scientific Affairs,
and S. Verbanck was supported by the Federal Fund for Scientific
Research-Flanders (FWO). G. K. Prisk was partially supported by
NASA contract NAS9-98124, and C. Darquenne was supported by NASA Grant
NAGW-4372 and by a Parker B. Francis fellowship in Pulmonary Research.
Address for reprint requests and other correspondence: B. Dutrieue, Laboratoire de Physique Biomédicale, Route de Lennik, 808, CP 613/3, B-1070 Brussels, Belgium (E-mail:
bdutrieu{at}ulb.ac.be).
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.
September 6, 2002;10.1152/japplphysiol.00299.2002
Received 8 April 2002; accepted in final form 3 September 2002.
| |
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