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Department of Medicine, University of California, San Diego, La Jolla, California 92093; Akademisch Ziekenhuis, Vrije Universiteit Brussel, 1090 Brussels; and Biomedical Physics Laboratory, Université Libre de Bruxelles, 1070 Brussels, Belgium
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ABSTRACT |
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Top
Abstract
Introduction
Methods
Results
Discussion
References
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Prisk, G. Kim, Ann R. Elliott, Harold J. B. Guy, Sylvia
Verbanck, Manuel Paiva, and John B. West. Multiple-breath washin of helium and sulfur hexafluoride in sustained microgravity.
J. Appl. Physiol. 84(1): 244-252, 1998.
We performed multiple-breath washouts of
N2 and simultaneous washins of He
and SF6 with fixed tidal volume
(~1,250 ml) and preinspiratory lung volume (approximately the
subject's functional residual capacity in the standing position) in
four normal subjects (mean age 40 yr) standing and supine in normal
gravity (1 G) and during exposure to sustained microgravity (µG). The
primary objective was to examine the influence of diffusive processes
on the residual, nongravitational ventilatory inhomogeneity in the lung
in µG. We calculated several indexes of convective ventilatory
inhomogeneity from each gas species. A normal degree of ventilatory
inhomogeneity was seen in the standing position at 1 G that was largely
unaltered in the supine position. When we compared the standing
position in 1 G with µG, there were reductions in phase III slope in
all gases, consistent with a reduction in convection-dependent
inhomogeneity in the lung in µG, although considerable convective
inhomogeneity persisted in µG. The reductions in the indexes of
convection-dependent inhomogeneity were greater for He than for
SF6, suggesting that the distances
between remaining nonuniformly ventilated compartments in µG were
short enough for diffusion of He to be an effective mechanism to reduce
gas concentration differences between them.
humans; spaceflight; zero gravity; distribution of pulmonary ventilation; phase III of expiration; specific ventilation; intra-acinar inhomogeneity; convective inhomogeneity
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INTRODUCTION |
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Top
Abstract
Introduction
Methods
Results
Discussion
References
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INHOMOGENEITY OF VENTILATION is known to be caused by convective (bulk flow) processes and by interactions between diffusion and convection. The absence of gravity [microgravity (µG), weightlessness] has long been postulated to cause a reduction in the convective inhomogeneity of ventilation (1, 14). However, until recently, it was not possible to measure the behavior of the lung in µG.
During vital capacity maneuvers, a reduction in ventilatory inhomogeneity was observed in short periods of µG during parabolic flight (13) and in sustained µG (9). This reduction was in the convective component of the overall inhomogeneity of ventilation, as evidenced by marked reductions in the size of cardiogenic oscillations and the height of the terminal rise in gas concentration after the onset of airway closure. The observations were consistent with the removal of gravitationally induced distortion of the lung parenchyma.
However, only minor reductions in phase III slope were observed in transient and sustained µG (9, 13). This observation is consistent with model predictions of diffusion-convection-dependent inhomogeneity (DCDI) (16) and showed that, at the acinar level, considerable inhomogeneity of ventilation persisted irrespective of the presence or absence of gravity. More recently, by use of gases of widely differing diffusivity (He and SF6), it was shown that, although this inhomogeneity at the acinar level persists in µG, its nature was altered considerably (21). In normal subjects in normal gravity (1 G) the phase III slope was steeper for SF6 than for He because of the effects of DCDI at the acinar level and the more rapid diffusional spreading of He. However, in µG this slope difference was abolished, and the two slopes became the same. Furthermore, after a 10-s breath hold in µG, the slope difference was reversed, with the SF6 slope actually being flatter than the He slope. The genesis of this unexpected change is unknown, but it is likely due to a widespread change in acinar geometry, perhaps as a result of alterations in pulmonary blood volume, or to alterations in cardiogenic mixing as a result of altered propagation of the cardiac pressure wave through the lung.
In contrast to the results obtained during vital capacity maneuvers, µG resulted in only small changes in convection-dependent inhomogeneity (CDI) and DCDI when measurements were made with near-normal tidal volumes from functional residual capacity (FRC) (19). This surprising result indicates that, during normal breathing, inhomogeneities in lung mechanical properties, rather than gravitational distortion, are dominant in determining the inhomogeneity of ventilation. Use of an independent technique for measuring inhomogeneity of specific ventilation (SV) using rebreathing data collected in µG resulted in a similar conclusion (22).
We report the results of multiple-breath washout (MBW) studies performed in µG, in which tidal volume and preinspiratory lung volume (PILV) were fixed and He and SF6 were used as tracers in the test gas mixture. By fixing PILV, we eliminated the confounding influence of changes in FRC in different positions or in µG that limited the interpretation of previous data (19). The addition of small amounts of He and SF6 to the test gas mixture allowed us to examine the effects of diffusive gas mixing on the residual nongravitational inhomogeneity in the lung in µG. Because these gases differ widely in their diffusivity, their behavior in the periphery of the lung is markedly different, and these differences can provide information on the nature of the inhomogeneity. Data were collected during the 14-day Spacelab Life Sciences-2 (SLS-2) mission of the space shuttle Columbia. The results are compared with ground control studies carried out before and after the mission in the standing and supine positions.
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METHODS |
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Top
Abstract
Introduction
Methods
Results
Discussion
References
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Experimental system. We used the same experimental system used for previous studies of ventilatory inhomogeneity in µG (9, 19, 21). Briefly, the system centers around a bag-in-box with separate bags for inspired and expired gas. The subject breathes through a nonrebreathing valve, inspiring air or test gas. Flow was measured with a linearized (25) Fleisch no. 2 pneumotachograph in the wall of a bag-in-box system, and gas concentrations were measured with a rapidly responding magnetic sector mass spectrometer sampling at the lips of the subject, with all signals sampled at 160 Hz. Inspired gas was contained in a bag within the bag-in-box and was composed of 5% He-1.25% SF6-balance O2.
The system was arranged to allow the subject to act as the operator for all measurements, except those pre- and postflight measurements performed in the supine position, when assistance was provided. Subjects were trained to maintain a constant body position while standing and in µG, with their hands on the valves at the level of the mouthpiece. The mass spectrometer was calibrated immediately before and after use by sampling gases carried on board. These data were also used to determine and correct for fragment ion cross talk between channels. The flowmeter was calibrated by integration of the flow from strokes of a 3-liter calibration syringe. Mass spectrometer transit time was determined daily by measuring the time required for a sharp puff of gas containing CO2 to be detected by the mass spectrometer, and the data were then aligned accordingly. The time delay was taken as the time to the midpoint of the rise in CO2 and thus included the lag time and dynamic response time components. The total time delay was ~30 ms greater for SF6 than for He because of a 10-90% response that was ~30 ms greater than for He. On the basis of previous experience and simulation studies on test data, these differences are sufficiently small to be ignored in the context of these measurements.Subjects and data-collection schedule. The anthropometric data for the subjects are shown in Table 1. The subjects were numbered as in previous studies so that comparisons can be made. Subject 2 flew on SLS-1 and SLS-2 and retains her subject number. All subjects were healthy, nonsmokers for at least 2 yr before the start of data collection, had normal lung function, and reported no pulmonary problems.
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Test maneuver. The subject breathed air through the mouthpiece and, when comfortable, turned a valve beginning the test. The subject then expired to residual volume (RV), and this minimum volume was detected by the system. From this volume, a predetermined volume was added, defining the PILV to be used for the rest of the test. This volume was determined preflight in the standing position for each subject and set so that it was approximately equal to the subject's upright FRC. The same PILV was used for all tests performed on a subject, regardless of the posture or gravity level. Subjects were then prompted by the alphanumeric display to "breathe in," and the expiratory line was closed with large-bore solenoid valves, preventing exhalation. Once the inspired volume reached the PILV plus a predetermined tidal volume (typically ~1,250 ml; Table 1), the inspiratory line was closed, and simultaneously the expiratory valves opened and the subject was prompted to "breathe out." After exhalation of the preset tidal volume, the cycle repeated itself.
Three controlled breaths of air were taken in this manner, and then the subject was prompted to turn a rotary valve during exhalation so that the next inspiration was taken from the bag prefilled with the test gas mixture. The subject then continued to inspire the test gas, with tidal volume being controlled for 12 breaths. At the completion of breath 12 of the test gas, the subject was prompted to exhale to RV, completing the test.Data analysis. Data from each test were identified within the data stream, and calibrations were applied. To allow ready comparison between the resident gas washout (N2) and the nonresident gas washin (He or SF6) and to account for differences in the inspired concentrations of He and SF6, gas concentrations were normalized by considering the pretest concentration of gas in the lung as 100.0 and the inspired concentration of gas as 0.0. Thus N2 was simply rescaled to cover the range 0-100%, whereas He and SF6 were inverted and then rescaled to cover the range 0-100%. This results in all data appearing as a washout from an initial concentration of 100% to a final concentration of 0%, with positive phase III slopes for all gases.
Data were first corrected for mass spectrometer transit time, and the flow was converted to BTPS conditions. For each of the three tracer gases (N2, He, SF6), end-tidal gas concentrations were measured, and the mixed expired gas concentration was determined from the integration of the product of flow and instantaneous gas concentration. The cumulative expired gas volume over the course of the washout was also determined in milliliters (STPD). For all gases (N2, He, SF6) we calculated the distribution of SV (from end-tidal and mixed expired data), the slope ratio of the washout, the normalized phase III slope, and the contribution of CDI to the washout as detailed below.Distribution of SV. Distribution of SV was calculated using the method described by Lewis et al. (12). This calculation was performed twice for each washout: once for the mixed expired gas concentrations and once for the end-tidal gas concentrations. In both cases 50 compartments of SV were chosen to span the range of SV from 0.01 to 10 on a uniformly distributed logarithmic scale. The distribution of fractional ventilation values providing the best fit to the observed 12 breaths of gas concentration was then determined using the technique of enforced smoothing (12). The first two moments of the distribution (mean, log-SD) were then calculated.
Slope ratio of MBW. The logarithm of the mixed expired gas concentration was plotted as a function of lung turnover (cumulative expired volume divided by PILV). The slope of this relationship was then measured over the portion of the washout from 50 to 100% of total lung turnover and also over 10-50%, and the ratio of the slope of these two lines was calculated. The first 10% of the washout was not used in the calculation to exclude dead space effects in breath 1. This ratio has a value of unity in the case of a monoexponential washout and will be <1 when the behavior of the lung deviates from perfectly mixed (5).
Normalized phase III slope. The normalized phase III slope (Sn) for each exhalation was determined from the least-squares best-fit line of gas concentration fitted against volume over the range 700-1,200 ml of expired tidal volume for each breath (500-900 ml for subject 2). Phase III slope was expressed as the normalized expired slope (Sn) by dividing the slope by the end-tidal gas concentration for that breath (19). For each subject in each state, the progression of Sn with breath number was determined by averaging the values for each breath over each performance of the maneuver, and the results are expressed as means ± SE. For each data set, the final Sn (Snf) for the washout was determined as the average over the final two breaths. Snf was used by Crawford et al. (4, 5) to compare end points of washouts. We use it here because it allows a reduction of the noise associated with end points of the washouts when gas concentrations are very low.
Contribution of CDI.
The contribution of CDI to the overall washout was calculated using the
method outlined by Crawford et al. (4). Briefly, because the
contribution to the
Sn from DCDI
effects is essentially constant from breath
5 of the washout, any subsequent rise in Sn is due to CDI
effects. We calculated this effect as the slope of
Sn
per unit lung turnover obtained from a linear least-squares fit to the
Sn data from
breath 5 to breath
10 of the washout (beyond which noise in the gas
concentration signals is too large for accurate slope determination)
and use this index
(
SCDI)
directly.
PILV. PILV was calculated from the volume of N2 washed out over the course of the test maneuver. At the beginning of the washout, the lung was assumed to be uniformly filled with gas at ambient concentration (which was set to 100% by the calibration procedure described above). At the end of the washout the lung was assumed to be uniformly filled with gas at the end-tidal gas concentration of the last breath of the washout (typically <10%). By use of mass balance, the average PILV of the washout was then determined.
Statistical methods. We followed the procedure used in our earlier studies of pulmonary function in µG (7-9, 18-21). Subjects acted as their own controls. Statistical analysis was performed using Systat version 5.0 (Systat, Evanston, IL) or Microsoft Excel (Microsoft, Redmond, WA). Data were grouped according to subject and position (standing, supine, µG), and two-way analysis of variance was performed. In cases where there were significant F ratios, post hoc testing was performed using the Bonferroni adjustment to determine significance levels. Simple comparisons were performed using t-tests. Significance was accepted at P < 0.05, and values are means ± SE.
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RESULTS |
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Abstract
Introduction
Methods
Results
Discussion
References
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We found no significant differences in the variables between pre- and postflight. This is similar to our other studies on the distribution of ventilation in µG (9, 19, 21), and for that reason we report only the combined pre- and postflight (standing and supine) and in-flight (µG) results.
Sn. The Sn of N2 is shown in Fig. 1 for all four subjects. There was no consistent difference in Sn between the standing and supine positions in 1 G. Similarly, the Sn calculated over the final two breaths of the washout (Snf) was unaltered by position in 1 G. Although they are not shown, the equivalent plots for He and SF6 are qualitatively similar; however, the reduction in Sn over the course of the washout from 1 G to µG was considerably smaller for He than for SF6. There was no difference in the behavior of He or SF6 between the standing and the supine position.
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1) than in the
Sn for He
(0.028 ± 0.012 liter1) in µG means
that the SF6-He difference in
Sn is greatly
reduced in µG compared with the standing and supine positions in 1 G.
CDI contribution.
Figure 3 shows the results from the
washouts performed in the standing position and in µG. In µG,
SCDI was
reduced (but not significantly) for He and largely unaltered for
N2 and
SF6 (Fig. 3). The CDI contribution
to Sn
(SCDI) could
not be determined from the supine data because of the large effects on
Sn caused by
cardiogenic oscillations in this position.
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Distribution of SV. The distributions we obtained from the end-tidal gas concentrations in these very well controlled experiments were always unimodal. In subject 11 the distributions derived from mixed expired gas concentrations showed evidence of a second mode at high values of SV, but this was small. Because the distributions themselves are unremarkable, they are not included in this report. However, the mean and log-SD values for end-tidal and mixed expired data for each position and for each of the three gas species are shown in Table 2. Because we controlled tidal volume and PILV in each of the positions, the mean SV of the distributions is not indicative of the values that would normally be obtained in these positions but is increased due to the larger than normal tidal volume used. The mean SV values for each position are the same in all conditions when a specific gas is considered.
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Slope ratio of MBW. Slope ratios calculated between 10-50% and 50-100% of cumulative expired volume are shown in Table 2. With the exception of SF6, the smallest slope ratio (which indicates the greatest degree of inhomogeneity) was found in the supine position, although the differences were small. In µG the slope ratio for SF6 was reduced compared with the standing position (P < 0.00), and the reduction for He bordered on being statistically significant (P = 0.054). However, the slope ratio for N2 was unchanged.
Lung volumes. The mean tidal volumes of breath 1 of the washouts were 1,150 ± 23 (SE), 1,130 ± 28, and 1,220 ± 40 ml in standing and supine positions and in µG, respectively. The tidal volume in µG was significantly greater than that measured in the supine position. This small difference results from timing differences in the volume control systems used on the ground and in µG (19). As in the previous study (19), we consider these differences to be of minor physiological significance. Tidal volume measured in the standing position was not different from that measured in the supine position or in µG. There were no differences between the tidal volumes measured on successive breaths of the washouts.
PILV values as calculated from the N2 washout data were 2,985 ± 115, 2,917 ± 135, and 3,199 ± 216 ml in the standing and supine positions and in µG, respectively. There was no difference in PILV among the three positions. The volume between the PILV selected and maintained by the system and the subject's RV (effectively the expiratory reserve volume) was not different among positions, nor was it different between the beginning and end of the washouts.| |
DISCUSSION |
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Top
Abstract
Introduction
Methods
Results
Discussion
References
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Sn. In the previous study of MBW data in µG (19), we found a small increase in Sn in the supine compared with the standing position. In this study we fixed PILV to be the same in all three positions and, in doing so, eliminated any change that might be caused by changes in lung volume per se that, at least in 1 G, would tend to decrease Sn at lower lung volumes (3). Under these conditions of fixed lung volume, Sn was largely unaffected by gravitational orientation in 1 G (Fig. 1). This suggests that the degree of inhomogeneity caused by gravity during breathing at near-normal tidal volumes from FRC is largely independent of position, in contrast to the situation during vital capacity single-breath tests. It further suggests that the influence of the changes in thoracic blood volume that occur in transitioning from the standing to the supine position (18) is negligible with respect to its effect on the distribution of ventilation.
In contrast to the previous study (19), Sn was moderately reduced in µG over most of the washout in this study. We expected to see such a reduction in Sn if the CDI contribution to overall inhomogeneity were decreased, since there is clear evidence for a gravitational influence on alveolar ventilation (1, 10, 14), and we were surprised not to see such a reduction in µG in an earlier study (19). Removing the confounding influence of a change in PILV likely allowed us to see a reduction in Sn in this case. One of the most striking aspects of the Sn data is the difference in the magnitude of the reduction in Sn from 1 G to µG between He and SF6. Compared with the standing position, Sn was reduced in µG on average for all breaths by 0.028 ± 0.012 and 0.0640 ± 0.012 liter1 for He and
SF6, respectively. The reduction
occurred in all four subjects (Fig. 2) in whom a clear difference
exists between SF6 and He in
all the standing data (and in the supine data, although these are not
shown). However, in the µG data, this difference is much smaller. In
particular, for subjects 2 and
8, there is little difference in
Sn between
SF6 and He. These are the same two
subjects who exhibited negative
SF6-He phase III slope differences in vital capacity single-breath tests performed during the same Spacelab flight (21). A direct comparison is provided in Fig. 4, which plots the phase III slopes
recorded from vital capacity washouts of He and
SF6 performed without an
end-inspiratory breath hold (21) and the phase III slopes from
breath 1 of the multiple-breath study
reported here. The breath 1 data are
equivalent to a single-breath washout test performed starting at PILV
and with an inspiration of ~1,200 ml. Figure 4 shows that, as was the
case in the vital capacity breaths, there is a reduction in the
SF6-He phase III slope difference
in µG. However, the magnitude of this reduction is much smaller in
these breaths near tidal volume. A large part of the sloping alveolar
plateau is thought to be due to the interaction between convective and
diffusive transport processes that occur in a human at a zone about the
level of the entry to the acinus. For the more diffusive gas (He), this
zone is more proximal by two to three airway generations than it is for
the less diffusible gas (SF6)
(16). Modeling studies have shown that the critical determinant of
phase III slope due to these effects is the degree of volumetric
asymmetry and/or cross-sectional area asymmetry of daughter
branches in this zone. Thus a change in the difference between He and
SF6 slopes suggests a change in
acinar conformation due to the removal of gravity or a change in the
mechanics of gas mixing in this zone, perhaps as a result of changes in
cardiogenic mixing. The reduction in
SF6-He slope difference in µG
observed in this study also indicates that the changes in acinar gas
mixing previously reported for breaths that encompass lung volumes near RV and total lung capacity (21) are also operating, although to a
lesser extent, in breaths that are more representative of physiologically normal breathing.
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CDI contribution.
The slope of
Sn
as a function of breath number after breath
5 of the washout
(SCDI) is
due solely to CDI effects (4, 5). The
SCDI we
calculated indicates only a small (or no) reduction in the CDI
contribution for SF6 and
N2 in µG (Fig. 3). The result for N2 is consistent with our
previous study, in which we found only a modest reduction in the
inhomogeneity of ventilation measured with multiple-breath
N2 washouts (19), and with the
lack of change we see in other indexes of CDI in this study (e.g.,
log-SD) for N2 and
SF6. However, for He, there is a
substantial (although not statistically significant) reduction in
SCDI in µG.
This reduction is consistent with the notion that the (necessarily) nongravitational CDI persisting in µG is located in units that are
relatively close to one another, such that diffusion of a highly
diffusible gas is an effective mechanism to reduce concentration gradients set up by CDI. That a reduction in CDI is seen in the He data
suggests that this nongravitational CDI exists between acini or between
groups of a few acini.
SCDI).
The gravitational contribution to phase III slope may be estimated from
the phase III slopes of breath 1 [Sn(1)] in 1 G and µG. This
contribution {100 × [1 
Sn(1)
(µG)/Sn(1) (1 G)]} is relatively small in all gases: ~17%
for N2, 22% for He, and 15% for
SF6. The low value for the
gravitational contribution to phase III slope is consistent with
previous single-breath studies (9) and shows that the overall
contribution of gravity to phase III slope is small in normal subjects.
In a previous study (5) an upper limit of 28% was estimated for the
total CDI contribution, consistent with our estimates.
Distribution of SV. Although we calculated the distribution of SV from all three gases (N2, He, SF6), there was little to distinguish between the different gas species, except that in the standing position and in µG the log-SD of the distributions was consistently higher for SF6 than for He (Table 2).
The fact that the mean SV values were similar within a gas species independent of position is a good indication of the technical validity of these measurements. We fixed tidal volume and PILV to eliminate the influence of changes in lung volume per se on the inhomogeneity of ventilation. Previous studies have shown that measures of the inhomogeneity of ventilation vary markedly in the same subject when the studies are performed at different lung volumes (3, 17). In our previous studies of the multiple-breath N2 washout in µG, we found that resting FRC changed (19), as was the case in other studies of lung volume in µG (8). By controlling tidal volume and PILV, we sought to study the lung at a similar absolute lung volume to observe the effects of the removal of gravity on the inhomogeneity of ventilation. The difference between the mean SV measured by N2 and that measured by He or SF6 (the results of which were similar to each other, except in the case of the supine data, which are affected by cardiogenic oscillations) is likely caused by the effects of continuing gas exchange in the lung (2). Although we normalized the gas data so that the washin data appeared as washout data, washin gases will tend to reach their equilibrium concentration more rapidly as the shrinkage due to removal of respiratory gases concentrates them toward the inspired level. In contrast, the washout of the resident gas is delayed as the concentrating effect of gas exchange raises its concentration from the inspired (zero) level. Thus the effective PILV of a resident gas is lowered (less gas is washed out), raising the mean SV. The log-SD results from these washouts provide a direct measure of how evenly the inspired gas is distributed on the basis of convective flow. For N2, log-SD was greatest in the supine position and smallest in µG, although these differences were not significant. This is as might be expected from the effect of gravity on the convective distribution of gas in the lungs. In µG, where we would expect differences in alveolar size to be minimized, the distributions of SV are narrower than in 1 G, although again the differences were not significant. A similar result was seen in the previous study when PILV was not fixed (19). However, this study produces a more consistent result in the supine position than the earlier study, with log-SD generally being greater in the supine (less homogeneous) than in the standing position. This is similar to the effect seen in single-breath washouts (9, 21), which showed significantly greater inhomogeneity of ventilation in the supine than in the standing position. Direct comparison of log-SD for He and SF6 with that for N2 may not be valid, but because He and SF6 are washin gases, they may be compared with each other. To verify that the wider distributions for SF6 (larger log-SD) were not the result of more noise in the SF6 data, we performed a simple simulation. A typical He washout was analyzed using the techniques described and taken as a reference. Normally distributed random noise was added to these data at a level approximately twice that seen in the SF6 data, thus testing a worst-case scenario, and the analysis was repeated. This was performed eight times on the same data set, and the log-SD change was averaged. An increase of the noise in the signals resulted in no change in log-SD for the end-tidal data (0.5554 reference, 0.5548 ± 0.0037 SD, noisy simulations) or in the mixed expired data (0.6529 reference, 0.6536 ± 0.0011 SD, noisy simulations), indicating only a small sensitivity of log-SD to the noise levels in the underlying signals. In general, the log-SD was greater for SF6 than for He, although these differences were small. However, in the end-tidal data collected in µG, the log-SD for He was considerably less than that for SF6. This likely reflects the enhancement in alveolar mixing provided by the higher diffusivity of He. If significant CDI exists between closely placed units of lung, then diffusion will be an effective mechanism in reducing this inhomogeneity. Evidence for considerable nongravitational CDI has been obtained from experiments performed in µG (9, 19, 21, 22) and from studies of excised lungs (15, 23, 24). The markedly lower log-SD for He than for SF6 in µG is strong evidence for nongravitational CDI between lung units that are sufficiently close to each other that diffusion of He can reduce the concentration differences generated by CDI and is consistent with the calculations of CDI contribution performed above.Slope ratio of MBW. The slope ratio is affected by the degree of CDI in the lung. We had expected to see an increase in the slope ratio in µG and failed to observe this in the previous MBW study (19). We attributed this in part to the reduction in lung volume in µG. In this study we obtained absolute values for the slope ratio similar to those in the previous study and also failed to see an improvement in this index in µG, despite the fact that lung volume was held constant. In fact, SF6 showed a significant reduction in slope ratio (became more inhomogeneous) in µG, and the change for He bordered on statistically significant (Table 2).
This result confirms our previous observation that at normal or near-normal tidal volumes the bulk of the CDI-induced inhomogeneity of ventilation is nongravitational in origin and must, therefore, reflect differences in alveolar size or alveolar expansion between regions of the lung that are likely close together.Lung volumes. The differences in tidal volume (which was controlled by the system), although significant in a statistical sense, are sufficiently small to be ignored in a physiological sense, inasmuch as they are only 50-100 ml. In the previous MBW study (19), we also saw a higher tidal volume in µG than on the ground, which we attributed to differences in system timing with respect to closing of the valves. We believe the same to be the case here.
The constancy of the PILV above RV is a good indication of the degree of control we were able to impose on our subjects' breathing pattern and allows us to be very confident in the quality of our results. Similarly, the absolute PILV was unchanged between positions, suggesting that any changes in RV, such as have been seen previously (8), were sufficiently small so as to not perturb our measurements and allow us to compare the inhomogeneity of ventilation at similar absolute lung volumes.Ventilatory inhomogeneity during tidal breathing. Previous studies of ventilatory inhomogeneity in µG led to equivocal results. Single-breath washout studies have provided strong evidence for a marked reduction in CDI effects, as evidenced by reductions in markers of inhomogeneity such as the height of the terminal rise after airway closure and the size of the cardiogenic oscillations (9, 13). On the basis of previous studies of the effect of gravity on the lung (1, 10, 14), these reductions were expected. However, considerable inhomogeneity that was clearly convective in origin remained, indicating that regional differences in mechanical behavior of the lung play a significant role in the overall degree of convective inhomogeneity. In a recent study of the degree of SV derived from rebreathing data (22), it was concluded that, in 1 G, gravitationally independent convective inhomogeneities were at least as large as gravitationally dependent inhomogeneities.
These same single-breath studies cited previously (9, 13) showed that, in µG, most of the phase III slope persisted, indicating that considerable acinar inhomogeneity remains in µG. This was not unexpected, since inhomogeneity at the acinar level was expected to be largely independent of gravity. However, when He and SF6 single-breath washouts were studied in µG (21), marked changes in diffusion-dependent inhomogeneity occurred, with unexpected slope reversals between SF6 and He. This suggested widespread changes in acinar conformation or alterations in cardiogenic mixing in the lung. Similar studies in short periods of µG (25 s), however, failed to reproduce these results, suggesting that the time course leading to these alterations in acinar gas mixing was >25 s but less than several hours (11). This in turn suggested that changes in the vascular compartment must play a role, since the known time course of viscoelastic settling of the lung is on the order of only a few seconds (6). These studies also suggested that the principal change in acinar gas mixing in µG was in the more proximal He diffusion front, as opposed to the more distal SF6 diffusion front, consistent with the changes in He observed in this study. When multiple-breath N2 washouts were performed in the same subjects used for single-breath studies (9, 19), there were no significant reductions in the CDI components of ventilatory inhomogeneity, with the exception of a slight reduction in normalized phase III slope. These results were, however, somewhat confounded by the changes in PILV between the states studied. However, the overall conclusion from that study was that, during breathing close to that seen tidally, gravity played a largely unimportant role in the total amount of inhomogeneity seen in the normal human lung. The results of this study support that conclusion, with little or no change in CDI-dependent inhomogeneity in N2 or SF6, gases in which diffusion is less effective at abolishing the residual nongravitational concentration differences due to CDI. In conclusion, studies of MBWs in µG, performed at a fixed PILV and with tracers of differing diffusivity in the inspirate, largely confirm the somewhat surprising result of previous studies. Specifically, it appears that, despite reductions in CDI in the lung during large breaths, during tidal breathing, CDI remains largely unchanged in µG. However, on the basis of the calculations of the CDI contribution to total inhomogeneity, it appears that this nongravitational CDI may exist between lung units that are relatively close together (at the level of a single acinus or a few acini) where diffusion of He can reduce the concentration gradients generated by CDI. The changes in interacinar gas mixing likely stem from enhanced spreading of the diffusion front for He, possibly caused by changes in cardiogenic mixing. However, the exact mechanism of these changes is unclear.| |
ACKNOWLEDGEMENTS |
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We acknowledge the support and cooperation of the crew of SLS-2 and the National Aeronautics and Space Administration and Martin Marietta Services personnel who supported the mission. We also thank Jim Billups, Mel Buderer, Charlie Davis, Marsha Dodds, Brian Dubow, Gerald Kendrick, Pat Kincade, Janelle Fine, Mary Murrell, and Gloria Salinas.
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FOOTNOTES |
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This work was supported by National Aeronautics and Space Administration Contract NAS9-16037 and contract Prodex with the Belgian National Policy Office.
Address for reprint requests: G. K. Prisk, Dept. of Medicine, 0931, University of California, San Diego, 9500 Gilman Dr., La Jolla, CA 92093-0931.
Received 31 March 1997; accepted in final form 4 September 1997.
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REFERENCES |
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Abstract
Introduction
Methods
Results
Discussion
References
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