J Appl Physiol
91: 637–644, 2001.
Effects of hypergravity and anti-G suit pressure on
intraregional ventilation distribution during VC breaths
PER M. GUSTAFSSON,1,2 OLA EIKEN,1 AND MIKAEL GRÖNKVIST1
1
Swedish Defense Research Agency, Aviation Medicine, S-580 13 Linköping
and Karolinska Institutet, S-171 77 Stockholm; and 2Department
of Paediatrics, Central Hospital, S-541 85 Skövde, Sweden
Received 21 August 2000; accepted in final form 19 March 2001
seem to affect intraregional ventilation distribution
differently, which has led to speculations that changes
in pulmonary blood volume may influence ventilation
distribution in the lung periphery via still unknown
mechanisms (22).
In the present study, 10 healthy male test subjects
performed vital capacity (VC) single-breath washin/
washouts (SBW) of 4% SF6 and 4% He in a human
centrifuge during exposures to ⫹1, ⫹2, or ⫹3 Gz, with
or without pressurization (0, 6, and 12 kPa) of an
extended-coverage anti-G suit (AGS). The study aimed
to explore the influence of increased gravity on total
and intraregional ventilation distribution during VC
breaths and to assess the effects on ventilation inhomogeneity from the pulmonary vessel engorgement
and abdominal compression that result from inflating
an AGS.
On the basis of the findings in microgravity, we
hypothesized that total and intraregional inhomogeneity would both increase in hypergravity. Furthermore,
we hypothesized that pressurization of the AGS would
increase intraregional ventilation inhomogeneity by
translocation of blood into the thorax.
gravity; He; SF6; single-breath washout; ventilation inhomogeneity; vital capacity
METHODS
Subjects
INCREASED GRAVITY IN THE HEAD-TO-FOOT
direction (⫹Gz) is
known to impair the homogeneity of ventilation distribution between widely separated lung regions (interregional inhomogeneity) (4, 24) because of the increased pleural pressure gradient (13). Washin/
washout studies using two inert tracer gases with
markedly differing molecular mass (Mm) such as SF6
(Mm 146) and He (Mm 4) offer the possibility to assess
not only overall ventilation inhomogeneity but also
inhomogeneity between and/or within adjacent acinar
regions, i.e., intraregional inhomogeneity (8, 15, 27,
30). Studies in microgravity employing such methods
indicate that gravity influences both interregional and
intraregional ventilation distribution (18, 32). Interestingly, short-term (22) and sustained microgravity (32)
Address for reprint requests and other correspondence: P. M.
Gustafsson, Dept. of Paediatrics, Central Hospital, S-541 85 Skövde,
Sweden (E-mail: [email protected]).
http://www.jap.org
Ten volunteering test subjects, all specially trained for
centrifuge studies, were engaged in this study. They were all
nonsmokers and none of them had a history of chronic or
current respiratory conditions. Their mean ⫾ SD age, weight,
and height were 32 ⫾ 4 yr, 79 ⫾ 6 kg, and 180 ⫾ 7 cm,
respectively.
Equipment
The study was performed in the human centrifuge at
Karolinska Institutet, Stockholm, Sweden. All test subjects
were equipped with an extended-coverage AGS and positioned and strapped in a jet fighter seat in the centrifuge
gondola. The three inflatable bladders of this suit cover the
lower limbs from the ankles to the groin completely and the
abdomen up to the lower costal margins, i.e., slightly above
the umbilicus. The AGS was laced to snugly fit each test
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8750-7587/01 $5.00 Copyright © 2001 the American Physiological Society
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Gustafsson, Per M., Ola Eiken, and Mikael Grönkvist. Effects of hypergravity and anti-G suit pressure on
intraregional ventilation distribution during VC breaths. J
Appl Physiol 91: 637–644, 2001.—The effects of increased
gravity in the head-to-foot direction (⫹Gz) and pressurization
of an anti-G suit (AGS) on total and intraregional intraacinar ventilation inhomogeneity were explored in 10
healthy male subjects. They performed vital capacity (VC)
single-breath washin/washouts of SF6 and He in ⫹1, ⫹2, or
⫹3 Gz in a human centrifuge, with an AGS pressurized to 0,
6, or 12 kPa. The phase III slopes for SF6 and He over
25–75% of the expired VC were used as markers of total
ventilation inhomogeneity, and the (SF6 ⫺ He) slopes were
used as indicators of intraregional intra-acinar inhomogeneity. SF6 and He phase III slopes increased proportionally
with increasing gravity, but the (SF6 ⫺ He) slopes remained
unchanged. AGS pressurization did not change SF6 or He
slopes significantly but resulted in increased (SF6 ⫺ He)
slope differences at 12 kPa. In conclusion, hypergravity
increases overall but not intraregional intra-acinar inhomogeneity during VC breaths. AGS pressurization provokes
increased intraregional intra-acinar ventilation inhomogeneity, presumably reflecting the consequences of basilar pulmonary vessel engorgement in combination with compression of
the basilar lung regions.
638
SF6 AND HE SINGLE-BREATH WASHOUT IN HYPERGRAVITY
centrifuge was halted, and subsequently the AGS was deflated. A 3- to 5-min-long pause was taken between the runs,
allowing the test subjects to rest and all tracer gas possibly
remaining in the lungs to be exhaled.
The difference between the SF6 and He concentrations
(SF6 ⫺ He) was calculated sample by sample and plotted as
a function of expired volume. The phase III slopes for SF6,
He, and (SF6 ⫺ He) were calculated by linear regression
(least squares fit) over 25–75% of the expiratory volume from
TLC. All slopes were normalized by the mean slope concentration for each gas to avoid possible errors from differences
in inhaled tracer gas concentrations and from potential drift
in the mass spectrometer. For calculations and presentations, the SF6 and He phase III slopes were treated as
positive.
Ethics
The study was approved by the Ethics Committee for
Human Research at Karolinska Institutet, Stockholm.
Statistics and Data Presentation
Two- or three-way ANOVA tests were undertaken to estimate the overall effects of tracer gas, gravity level, AGS
pressure, and interaction effects on the parameters were
assessed. The P values from the ANOVA are given when
appropriate. Post hoc comparisons were undertaken using
the Tukey honest significant difference test. P values ⬍0.05
were regarded as statistically significant. Data are presented
as means ⫾ SE. The statistical analysis was performed by
use of the Statistica 5.5 Software (StatSoft, Tulsa, OK).
RESULTS
VC
VC tended to be lower (1.7%) in ⫹2 Gz than in ⫹1 Gz
and was significantly lower in ⫹3 Gz (5.1%; P ⬍ 0.001)
when an AGS pressure of 0 kPa was used. In normogravity, VC was on average 7.5% lower when the AGS
pressure was 6 kPa, and 17.8% lower when the pressure was 12 kPa, compared with 0 kPa AGS pressure
(P ⬍ 0.001; Fig. 1). When the AGS was pressurized, the
Test Procedures and Evaluation
The SBW procedure was carried out in a randomized order
in ⫹1, ⫹2, or ⫹3 Gz, with an AGS inflation pressure of 0, 6,
or 12 kPa at each level. A nose clip was used during all tests.
Three VC SBW maneuvers were performed in each test
condition, resulting in a total of 27 washouts. The tests began
by pressurizing the AGS, before the centrifuge was started.
Gravity was allowed to increase at a rate of 0.1 Gz/s until the
desired ⫹Gz level was reached. After 30 s of acclimatization
at the respective gravity level, the VC SBW procedure was
performed. Air was administered at the start of the procedure. During expiration to residual volume (RV), the solenoid
was switched, resulting in administration of the 4% SF6 and
He gas mixture during the subsequent inspiration to total
lung capacity (TLC). Inspiration was performed at a target
flow of 0.5 l/s. The test subjects were instructed not to make
a postinspiratory pause. Expiration started at TLC and was
also performed with a flow of 0.5 l/s until RV was reached.
Gravity was then decreased at a rate of 0.2 Gz/s until the
J Appl Physiol • VOL
Fig. 1. Expiratory vital capacity (VC) in relation to anti-G suit (AGS)
pressure and gravitational load (⫹Gz). Error bars (SE) are given for
⫹1 Gz and ⫹3 Gz only. ***P ⬍ 0.001, VC at ⫹3 Gz vs. ⫹1 Gz, with 0
kPa AGS pressure; †††P ⬍ 0.001, VC at 6 kPa vs. 0 kPa AGS
pressure at ⫹1 and ⫹2 Gz; ###P ⬍ 0.001, VC at 12 kPa vs. 0 kPa AGS
pressure in ⫹1, ⫹2, and ⫹3 Gz.
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subject. Gas mixtures (air or a mixture of 4% SF6, 4% He,
21% O2, balance N2) were directed to the gondola from two
gas cylinders positioned in the rotary center of the centrifuge.
The gases were further administered via a demand valve
(OTWO-systems, Toronto, ON, Canada), through a two-way
breathing valve (model 2630; Hans Rudolph, Kansas City,
MO), and finally via a pneumotachometer (PTM) and a
mouthpiece to the test subject. The dead space of the breathing system was ⬃70 ml. Either gas was provided by manually
controlled solenoids. Inspiratory and expiratory flows were
measured by a heated Fleisch no. 2 PTM attached to the
two-way valve. Gas concentrations were measured at the
mouth by an AMIS 2000 respiratory mass spectrometer (Innovision A/S, Odense, Denmark), placed in the center of
rotation of the centrifuge. All signals were sampled at a rate
of 100 Hz each by a digital Pentium computer, equipped with
a 16-channel analog-to-digital conversion board using custom-made software.
The PTM was calibrated with a 3,000-ml precision syringe
(Hans Rudolph) at a flow of ⬃0.5 l/s. Separate calibration
constants for inspiratory and expiratory flow rates were
calculated. Recorded inspiratory and expiratory flow rates
and volumes were converted to BTPS conditions. Proper time
alignment of gas concentration and flow signals was achieved
by the technique described by Brunner et al. (3). The tip of
the mass spectrometer capillary was positioned in the center
of the air stream, between the mouthpiece and the PTM, and
the sample rate was 20 ml/min. The mass spectrometer
measured the concentrations of all respiratory gases used
(SF6, He, N2, O2, and CO2), except water vapor, i.e., dry gas
concentrations. The gas concentration signals were updated
at a rate of 33.3 Hz. The software corrected the flow signal
sample by sample for changes in dynamic viscosity caused by
the variations in gas composition. Validation of the function
of the measurements was performed before and after completion of the measurements in each test subject. Multiplebreath washouts of tracer gas were then done by using the
3,000-ml precision syringe, i.e., simulating functional residual capacity (FRC) measurements. The accuracy of the measured syringe volumes was within 3% of the geometric volume (3,000 ml), and the precision was also within 3%. During
the tests, inspiratory and expiratory flows and volumes were
monitored on a computer screen placed in front of the test
subjects. This visual feedback allowed the test subjects to
perform the VC maneuver with the desired respiratory flow
of 0.5 l/s.
SF6 AND HE SINGLE-BREATH WASHOUT IN HYPERGRAVITY
639
level of gravity had no significant influence on VC.
Three-way ANOVA (flow direction, gravity, and AGS
pressure) disclosed no significant difference between
the inspiratory and expiratory volumes measured during the VC maneuvers (P ⫽ 0.54).
Respiratory Flow and Timing
SF6 and He Phase III Slopes
In all test situations, the phase III slopes were significantly steeper for SF6 than for He (P ⬍ 0.001; Fig.
2). The phase III slopes for both SF6 and He increased
significantly in a stepwise fashion with increased gravity irrespective of AGS pressures (P ⬍ 0.001; Fig. 2).
With an AGS pressure of 0 kPa, the phase III slope
increased on average 25% and 33% in ⫹2 Gz and 42%
and 63% in ⫹3 Gz for SF6 and He, respectively, compared with the findings in normogravity. No significant
overall influence from AGS pressure on the SF6 or He
phase III slopes was found, but there was a statistically significant so-called interaction effect between
gas and AGS pressure (P ⬍ 0.001; Fig. 2): in ⫹3 Gz the
average SF6 phase III slope remained unchanged between AGS pressures of 6 and 12 kPa, whereas the He
slope decreased at 12 kPa.
(SF6 ⫺ He) Phase III Slopes
Increased gravity had no significant influence on
the (SF6 ⫺ He) phase III slopes (Fig. 3). On the other
hand, increased AGS pressure had a significant effect on (SF6 ⫺ He) phase III slopes (P ⬍ 0.001). The
average slope values were markedly greater at an
AGS pressure of 12 kPa than at 6 or 0 kPa (P ⬍
0.001; Fig. 3).
DISCUSSION
Overview of the Results
This SBW study confirms the findings from previous
studies (2, 4, 24) showing that overall ventilation distribution is substantially influenced by gravity. SecJ Appl Physiol • VOL
Fig. 2. SF6 (A) and He (B) phase III slopes in relation to AGS
pressure and ⫹Gz. ***P ⬍ 0.001, comparison between slopes at all 3
levels of gravity.
ondly, the study extends the previous observations by
demonstrating that intraregional intra-acinar ventilation inhomogeneity does not change significantly with
increased gravity in the range of ⫹1 to ⫹3 Gz when a
VC breath is taken. An even more interesting and
important finding is that the inflation of the AGS
provoked a significant impairment of gas mixing between and within the most distal airways as manifested by increased (SF6 ⫺ He) phase III slopes. Finally, we found that VC decreased markedly when the
AGS was pressurized but only slightly when gravity
was increased.
Several factors are likely to influence the phase III
slope (e.g., the intrathoracic blood volume, gravity per
se, VC, and AGS pressure). Their roles have been
elucidated by other authors in several previous papers.
These factors will be discussed below one by one to
facilitate the interpretation of the changes in the phase
III slopes and the physiological events involved. First,
however, a short review of the theory of gas mixing in
the lungs is given.
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On the whole, mean values of inspiratory flows were
only slightly but statistically significantly higher than
expiratory flows (0.45 vs. 0.42 l/s; P ⬍ 0.001). Average
expiratory or inspiratory flows did not vary with the
level of gravity but decreased slightly with increased
AGS pressure from 0 to 12 kPa (0.01 l/s; P ⬍ 0.05). The
recorded average inspiratory and expiratory flows were
all slightly lower than the flow that the test subjects
were instructed to maintain (0.50 l/s). Because of the
decrease of VC and the constant average respiratory
flows, the inspiratory and expiratory times decreased
significantly with increased gravity and AGS inflation
pressure. The inspiratory time decreased from 12.0 ⫾
2.0 s in ⫹1 Gz with nonpressurized AGS to 9.6 ⫾ 2.1 s
in ⫹3 Gz at an AGS pressure of 12 kPa (P ⬍ 0.001). For
expiratory time, the corresponding figures were 12.9 ⫾
2.5 and 9.3 ⫾ 4.1 s, respectively (P ⬍ 0.001). The
average postinspiratory pause time was 0.27 s and did
not vary between test conditions.
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SF6 AND HE SINGLE-BREATH WASHOUT IN HYPERGRAVITY
Fig. 3. (SF6 ⫺ He) phase III slopes in relation to AGS pressure and
⫹Gz. ***P ⬍ 0.001, comparison of mean slopes at AGS pressure of 12
kPa vs. 6 kPa and vs. 0 kPa, respectively.
The phase III slope of an inert marker gas reflects in
part the combined influence of all unequally and sequentially ventilated parallel airway regions on gas
mixing (12). Previous lung modeling and experimental
studies (15, 27, 30) have established the mechanisms
that determine the phase III slope. Ventilation distribution in the human lung is determined by gravity, i.e.,
through the gravity-dependent pleural pressure gradient, and by other factors not related to gravity (12, 13).
During normal tidal breathing, most of the inhomogeneity of ventilation distribution in the normal lung is
the result of inhomogeneity in the most distal air
spaces (8). The mechanisms contributing to the SBW
phase III slope, an indicator of overall inhomogeneity,
have been summarized (32) as follows: 1) Gravitational
convection-dependent inhomogeneity (CDI), produced
by differences in expansion between the top and the
bottom of the lung and sequential lung emptying (24).
SBW studies in microgravity suggest that gravitational CDI causes ⬃25–30% of all inhomogeneity (18,
23). 2) Nongravitational CDI, which results from inhomogeneity within and between separate regions due to
variations in mechanical properties that are not caused
by gravity (26, 34). 3) Diffusion-convection interactiondependent inhomogeneity (DCDI) at the diffusion-convection front in the distal airways and air spaces.
DCDI is the major contributing mechanism to inhomogeneity during normal breathing in healthy subjects
(8, 15).
The diffusion-convection front is the region of the
airways where the influence of diffusion and convection
on the movement of gas molecules is of equal magnitude. The diffusivity of a gas is inversely proportional
to the square root of its Mm, and because the Mm of
SF6 is 146 and for He 4, the diffusivity of He is approximately six times greater than for SF6. In the normal
human lung, the front for SF6 is predicted to form
within the acini, and the phase III slope for SF6 reflects
the degree of ventilation inhomogeneity that exists
J Appl Physiol • VOL
Methodological Aspects
The phase III slope was determined from 25 to 75%
of the expired VC in this study. Other authors have
used slightly different criteria and an interactive procedure for determination of the limits of phase III (10,
13, 32). In the recordings from all our subjects, the
chosen interval started after the end of phase II and
ended before the start of phase IV. Another possibility
would have been to use absolute lung volumes to indicate the limits of the phase III interval. When the AGS
was not inflated, VC was 1.7% lower in ⫹2 Gz and 5.1%
lower in ⫹3 Gz than in normal gravity. Such small
changes would not invalidate the use of relative reference points for the phase III slope interval. With AGS
inflation there were, however, substantial reductions
in VC. At an AGS pressure of 6 kPa, VC was 4–7%
lower and at 12 kPa 11–19% lower compared with the
0-kPa AGS pressure conditions. It would have been of
interest to apply absolute lung volumes as reference
points for phase III slope calculation in these conditions. Such a procedure would have to be based on the
assumption that one static lung volume, e.g., the RV,
could serve as a reference volume. In the present study,
we did not measure RV, and therefore we felt that we
had no solid ground for changing the way of analyzing
the slopes. For the (SF6 ⫺ He) phase III slope, a
possible difference in the limits of the interval would
probably matter less than for the two gases measured
separately.
The time allowed for diffusion of the inert tracer
gases during inspiration and expiration is important,
because diffusion will reduce the differences in the
distribution of the two gases within small regions.
Although the mean inspiratory and expiratory flows
did not vary significantly with gravity or inflation pressure, inspiratory and expiratory time did differ
slightly, reflecting the reductions in VC. However, the
time differences noted between the conditions are not
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Theory
within acini plus that which exists between parallel
regions that branch more proximally (27, 28). The front
for He is predicted to form some generations mouthward of the SF6 front at the terminal bronchiole and/or
more proximally, and thus it reflects inhomogeneous
ventilation between groups of acini (27, 28). These
differences are the result of branching geometry, which
is more nonuniform in the distal airways of human
lungs (19, 28), with unequal cross-sectional areas or
volumes at the branch points (15). Proximal to the
diffusion-convection front for each gas, CDI makes its
contribution to the phase III slope for that particular
gas. Whereas the CDI components of the phase III
slope from SF6 and He are almost identical, the DCDI
components will differ because of the more peripheral
location of the diffusion-convection front for SF6. The
(SF6 ⫺ He) phase III slope will consequently reflect
intraregional intra-acinar ventilation inhomogeneity.
Gas exchange is known to contribute ⬃10% additional
heterogeneity during exhalation (6), but this effect is
equal for SF6 and He.
SF6 AND HE SINGLE-BREATH WASHOUT IN HYPERGRAVITY
great enough to invalidate the recorded phase III slope.
The average end-inspiratory pause time was ⬍0.5 s
throughout, which should not affect the phase III slope
results significantly (7).
A longer duration of hypergravity would presumably
result in more blood pooling in the lower body half
when AGS was not inflated. The SBW maneuvers were
undertaken after ⬃30 s at the predetermined ⫹Gz level
only. Therefore we could not assess the importance of
the duration of the gravitational stress on the parameters recorded. Furthermore, the present study does
not separate between the effects on lung function resulting from compression of the lower limbs (i.e., pulmonary vessel engorgement) and the abdomen (i.e.,
basilar lung compression), respectively.
VC Changes
J Appl Physiol • VOL
microgravity might be the result of blood shift into the
thorax, consistent with a previous report on the relationship between body posture and the intrathoracic
blood volume (33).
Short-term microgravity. The VC changes were not
reported from the short-term microgravity parabolic
flight studies by Michels and West (23) or by Lauzon et
al. (22). Paiva et al. (29) reported an 8% reduction in
VC during transient weightlessness, and Dutrieue et
al. (10) found a 17% reduction in inspiratory VC and no
change in RV in short-term microgravity compared
with the ⫹1 Gz control.
Immersion. Head-out immersion studies have unambiguously demonstrated that ⬃80% of the decline in
VC seen in this condition is caused by intrathoracic
blood pooling and that the restriction of the chest wall
movements from the external hydrostatic pressure has
little importance (1, 5, 9, 21).
Body position and blood pooling. At least 500 ml of
blood may be shifted to the lower limbs when subjects
assume the upright position from supine in normogravity (20). Sjöstrand (33) combined plethysmographic
and spirometric methods and showed that 80% of the
pooled blood when erected was drained from intrathoracic organs. Henry (20) demonstrated that an increased intrathoracic pressure of 60 mmHg resulted in
an additional pooling of blood of 150–500 ml in the
lower limbs. A similar effect will occur with a threefold
increase of gravity when the hydrostatic pressure gradient between heart level and the thighs increases by
⬃80 cmH2O (⬃60 mmHg). Combined, the results of
these earlier studies indicate that a total of over 1,000
ml of blood may be pooled into the lower limbs in ⫹3 Gz
in the upright compared with the supine position in
normogravity.
In the present study, the restricted chest movements
imposed by the increased weight of the chest wall in
hypergravity would tend to lower VC. On the other
hand, hypergravity would tend to raise VC by decreasing the intrathoracic blood volume, because venous
blood return is impaired. When the AGS is inflated in
normal and especially in increased gravity, large blood
volume shifts into the thorax may occur. The resulting
pulmonary vessel engorgement is probably the most
important mechanism behind the marked decrease of
VC that we found when the AGS was pressurized in
hypergravity. To establish the relative contributions of
AGS pressurization on VC from purely mechanical
external restrictions and from translocation of blood
into the thorax, it would be necessary to compress the
abdomen and the lower limbs separately. Both mechanisms are likely to impair the homogeneity of ventilation distribution, particularly in hypergravity.
Overall Ventilation Inhomogeneity and Gravity
Hypergravity. In the present study, the phase III
slopes, indicators of overall ventilation inhomogeneity,
increased by 25 or 33% in ⫹2 Gz and by 42 or 63% in ⫹3
Gz compared with ⫹1 Gz (SF6 and He, respectively),
whereas inflation of the AGS had no significant impact
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The physiological events responsible for the VC
changes in response to hypergravity and AGS pressurization are essential to understand because they may
be the key to understanding the mechanisms of increased intraregional ventilation inhomogeneity. In
the present study, VC decreased only slightly with
increased ⫹Gz when the AGS was not inflated. After
inflation of the AGS, VC decreased significantly but
was not further influenced by gravity. Previous observations on VC changes in response to hypergravity,
sustained or short-term microgravity, and immersion
will therefore be discussed in detail.
Hypergravity. In a summary of his extensive studies,
Glaister (17) reported that there was little change in
VC or RV measured after 30 s of stabilization in ⫹3 Gz,
but in ⫹4 Gz TLC was reduced by 5% in five test
subjects with no concomitant change in RV. In ⫹5 Gz,
VC was reduced by 15% (one subject). It was, however,
also reported that some other test subjects demonstrated a small decrease in VC in ⫹3 Gz (17), in agreement with the present findings. Glaister also showed
that the diaphragm descended 1 cm in ⫹2 Gz and 2 cm
in ⫹4 Gz, with concomitant increases in resting lung
volume of 300 and 500 ml, respectively (17). He further
reported that inflating an AGS to a pressure of 21 kPa
in ⫹1 Gz forced the diaphragm upward by 1 cm and
decreased the FRC by 500 ml. Interestingly, the descent of the diaphragm during hypergravity was not
prevented by the AGS inflation, but it was less pronounced with the AGS inflated than without such
protection. In the interval from ⫹1 to ⫹3 Gz, lung
compliance remained constant, but overall thoracic
compliance decreased linearly with gravity up to ⫹4
Gz, and this was consequently attributed to a decrease
in the compliance of the chest wall (17).
Sustained microgravity. Guy et al. (18) reported that
VC had decreased by 5% on flight day 2 in space,
but was normalized on day 4 and 9. Elliot et al. (11)
also reported that VC was lower in the first few days
of microgravity. From the Spacelab Life Sciences-2
(SLS-2), Prisk et al. (31) reported that VC increased on
average 6.1% (370 ml) after flight day 3. They proposed
that the consistent decrease of VC early in sustained
641
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SF6 AND HE SINGLE-BREATH WASHOUT IN HYPERGRAVITY
J Appl Physiol • VOL
Fig. 4. A: average percent change of VC single-breath washin/washout (SBW) SF6 and He phase III slopes from normogravity to sustained microgravity (Ref. 32) and to hypergravity (present study). B:
average percent change of VC SBW SF6 and He phase III slopes from
normogravity to short-term microgravity (Ref. 22) and to hypergravity (present study).
plotted percent changes of the He phase III slope from
normogravity to hypergravity reported here (R2 ⫽
0.999; Fig. 4A). But for SF6, there seems to be a slightly
better linear fit between the short-term microgravity
data and our results (Fig. 4B).
(SF6 ⫺ He) Phase III Slopes
In this study, we found no significant effect of increased gravity on the (SF6 ⫺ He) phase III slope,
indicating that hypergravity did not influence intraregional intra-acinar ventilation inhomogeneity. When
the AGS was inflated to a pressure of 12 kPa, but not to
6 kPa, the (SF6 ⫺ He) phase III slope increased significantly, indicating impaired intraregional intra-acinar
homogeneity, irrespective of ⫹Gz level.
Microgravity. In their bolus study, Dutrieue et al.
(10) reported that when the bolus was inhaled at low
lung volumes the resulting (SF6 ⫺ He) phase III slopes
indicated greater inhomogeneity for SF6 than for He.
When the bolus was inspired in the middle range of
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on overall inhomogeneity. Bryan et al. (4) measured
regional variations in lung volume and expansion with
133
Xe in ⫹1 to ⫹3 Gz. They found that the lung was
relatively more expanded at the top than at the bottom
in ⫹1 Gz and that ventilation was greater at the bottom when inspiring above FRC. These differences became greater during acceleration. The pleural pressure
gradient was indirectly measured in the esophagus
and was found to be twice as great in ⫹2 Gz vs.
normogravity (4). The effect of hypergravity on overall
ventilation distribution (SF6 and He phase III slopes)
in the present study is thus consistent with that reported by Bryan et al. (4).
Microgravity. No previous reports have been published using VC single-breath SF6 and He washout
tests to assess the effects of increased gravity on ventilation distribution, but several studies have been
undertaken in microgravity (10, 22, 32). From the
SLS-1 experiments (sustained microgravity), Guy et al.
(18) reported a 22% reduction in the phase III slope of
N2 during a VC breath. The initial 150-ml portion of
inspired gas during the preceding VC washin maneuver contained 79% Ar and 21% O2, and the remaining
inspired gas was 100% O2. The Ar phase III slope
decreased more markedly to 29% of the standing control value. This was expected because inhalation of an
inert tracer early in the breath will visualize any topographic sequencing between unevenly ventilated lung
spaces very clearly as an increased phase III slope (14).
In the SLS-2 study, Prisk et al. (32) found that the He
phase III slope decreased by 28% and the SF6 slope by
46% compared with the erect normogravity condition.
Lauzon et al. (22) performed VC SBW of SF6 and He in
eight subjects (five men) in short-term microgravity
(parabolic flights) and reported that the phase III slope
for He decreased by 66% and for SF6 by 37%. The
relative decrease of the He phase III slope was thus
twice as great in short-term microgravity to that in
sustained microgravity. Dutrieue et al. (10) performed
He and SF6 VC SBW in six subjects in short-term
microgravity and normogravity when the tracer gases
were inhaled over the whole VC or as discrete boluses
at various points over the inspiration. They found that
the phase III slope from the SBW could be correctly
reconstructed from individual bolus test. Most of the
slope was the result of events when inspiring below the
closing capacity or near TLC, and gravity-related
events at low and high lung volumes accounted for the
differences in phase III slopes between microgravity
and ⫹1 Gz for the two gases (10).
Fig. 4 shows plots of the relative changes in the
phase III slopes obtained for He and SF6 from normogravity to sustained microgravity in the SLS-2 study
(32) and from normogravity to short-term microgravity
in the Lauzon study (22). The changes measured in the
present study during hypergravity are also included.
Absolute values of changes in the phase III slopes in
the different studies are not given in the figures because different ways of normalizing the phase III
slopes were used in the studies. The He SLS-2 data
seem to fit strikingly well in a linear fashion with the
SF6 AND HE SINGLE-BREATH WASHOUT IN HYPERGRAVITY
microgravity and hypergravity are more pronounced
near RV then near TLC. The relative changes of the He
slope in response to gravity, given in Fig. 4A, would
consequently reflect changes in the geometry of the
small airways mouthward of the acini occurring at a
very low inspiratory level (near RV).
Other Reports on the Effects of Hypergravity and
AGS Pressurization
In a parallel study to the present one (Gronkvist M,
Bergstan E, Eiken O, and Gustafsson PM, unpublished
observations), we recently measured the volume of
trapped gas and assessed overall ventilation distribution from tidal breathing SF6 washouts in 10 healthy
male test subjects exposed to the same conditions as in
the present study. There was a slight but statistically
significant increase of ventilation inhomogeneity and
gas trapping with increased gravity. When the AGS
was inflated, gas trapping but not ventilation inhomogeneity increased markedly. These findings indicate
the appearance of widely spread airway closures in the
basilar lung regions and agree with those by Glaister
(17), who demonstrated airway closures during tidal
breathing by following the washout of intravenously
injected 133Xe. In ⫹1 Gz, the 133Xe washout followed a
single exponential curve, with a time constant proportional to the regional ventilation per unit volume. In
⫹3 Gz, with inflated AGS, however, the basilar washout curve had two components, one being very slow
(17). Modell and Baumgardner (25) measured the intrapleural pressure in dogs during gravitational stress
and simulation of the effect of AGS inflation. Their
study indicated that the pressurized suit caused positive pleural pressures over a significant portion of the
lung with a magnitude great enough to cause lung
compression and gas trapping. Glaister (16) also studied the lungs of a dog exposed to ⫹1 Gz for 4.75 h and
to six 1-min exposures of up to ⫹4 Gz and reported that
Fig. 5. Average relative change of VC SBW
(SF6 ⫺ He) phase III slopes from normogravity to
sustained microgravity with or without breath
holding (Ref. 32), to short-term microgravity
(Ref. 22), and to normogravity with pressurized
AGS and to hypergravity with or without pressurized AGS (present study).
J Appl Physiol • VOL
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VC, the resulting phase III slopes were very small for
both tracer gases, and the (SF6 ⫺ He) phase III slope
difference was minimal. With bolus inspiration at high
lung volumes, the resulting (SF6 ⫺ He) phase III slopes
indicated greater inhomogeneity for He than for SF6
(10). Prisk et al. (32) found that the positive normalized
(SF6 ⫺ He) phase III slope in normogravity was abolished in sustained microgravity, and with breath hold
it became negative, indicating more inhomogeneity for
He than for SF6. Lauzon et al. (22) reported an even
greater reduction in the He and SF6 phase III slopes
during short-term weightlessness. Because of a greater
reduction in the slope for He than for SF6, the (SF6 ⫺
He) phase III slope became greater in microgravity,
indicating greater inhomogeneity in the distal air
spaces (22).
Fig. 5 illustrates the relative changes in the (SF6 ⫺
He) phase III slopes from the normogravity condition
to weightlessness as reported in previous studies (22,
32) and to hypergravity in the present study. It is
apparent that conditions involving a sudden increase
in the intrathoracic blood volume, such as short-term
weightlessness and AGS inflation, are accompanied by
increased (SF6 ⫺ He) phase III slopes when a VC
breath is taken. The intrathoracic blood volume is
probably increased also during the first few days of
sustained microgravity, as indicated by the reduced VC
at this time. Further on (by day 3 and later), the VC
may be increased, suggesting that the intrathoracic
blood volume could then be reduced compared with
normogravity (18, 31).
The best agreement of relative changes in the phase
III slope in sustained microgravity and hypergravity
was seen for He (Fig. 4A). The He phase III slope
changes presumably reflect conformational events
mouthward of the acini. The phase III slope of a VC
breath in turn reflects inhomogeneities occurring near
RV and TLC, respectively (10). It may be presumed
that the differences of the phase III slopes between
643
644
SF6 AND HE SINGLE-BREATH WASHOUT IN HYPERGRAVITY
We acknowledge the skilful technical assistance given by Eddie
Bergsten, Roger Kölegård, and Bertil Lindborg.
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most alveoli from the basilar lung regions appeared as
“closed off vacuoles in an otherwise solid tissue.”
On the basis of the studies above, we believe that
there is convincing evidence that gas trapping due to
widely spread closures in the most distal airways took
place in the basilar lung regions when our test subjects
were exposed to ⫹3 Gz with the AGS inflated to 12 kPa.
The concomitant increase of the (SF6 ⫺ He) phase III
slopes when large breaths are taken reflects intraregional inhomogeneity, presumably within the lung
bases, due to lung compression and basilar pulmonary
vessel engorgement.
In conclusion, increased gravity in the head-to-foot
direction results in increased overall but not intraregional intra-acinar ventilation inhomogeneity when
a VC breath is taken. Inflation of an AGS, especially in
hypergravity, results in increased intraregional intraacinar ventilation inhomogeneity presumably due to
pulmonary vessel engorgement and basilar lung compression.