Journal of Applied Physiology AJP: Endocrinology and Metabolism
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

J Appl Physiol 91: 637-644, 2001;
8750-7587/01 $5.00
This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF) Free
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via ISI Web of Science (7)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Gustafsson, P. M.
Right arrow Articles by Grönkvist, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Gustafsson, P. M.
Right arrow Articles by Grönkvist, M.
Vol. 91, Issue 2, 637-644, August 2001

Effects of hypergravity and anti-G suit pressure on intraregional ventilation distribution during VC breaths

Per M. Gustafsson1,2, Ola Eiken1, and Mikael Grönkvist1

1 Swedish Defense Research Agency, Aviation Medicine, S-580 13 Linköping and Karolinska Institutet, S-171 77 Stockholm; and 2 Department of Paediatrics, Central Hospital, S-541 85 Skövde, Sweden


    ABSTRACT
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES

The effects of increased gravity in the head-to-foot direction (+Gz) and pressurization of an anti-G suit (AGS) on total and intraregional intra-acinar 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.

gravity; He; SF6; single-breath washout; ventilation inhomogeneity; vital capacity


    INTRODUCTION
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES

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) 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.


    METHODS
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES

Subjects

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 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. Multiple-breath 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.

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 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
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES

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 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).


View larger version (12K):
[in this window]
[in a new window]
  		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; dagger dagger dagger 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.

Respiratory Flow and Timing

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.

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.


View larger version (15K):
[in this window]
[in a new window]
  		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.

(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).


View larger version (12K):
[in this window]
[in a new window]
  		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.


    DISCUSSION
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES

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. Secondly, 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.

Theory

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 interaction-dependent 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 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.

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 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

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 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 on overall inhomogeneity. Bryan et al. (4) measured regional variations in lung volume and expansion with 133Xe 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 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).


View larger version (16K):
[in this window]
[in a new window]
  		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).

(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 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).


View larger version (15K):
[in this window]
[in a new window]
  		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).

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 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 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 intra-acinar ventilation inhomogeneity presumably due to pulmonary vessel engorgement and basilar lung compression.


    ACKNOWLEDGEMENTS

We acknowledge the skilful technical assistance given by Eddie Bergsten, Roger Kölegård, and Bertil Lindborg.


    FOOTNOTES

Address for reprint requests and other correspondence: P. M. Gustafsson, Dept. of Paediatrics, Central Hospital, S-541 85 Skövde, Sweden (E-mail: pmgmed{at}artech.se).

The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Received 21 August 2000; accepted in final form 19 March 2001.


    REFERENCES
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES

1.   Agostoni, E, Gurtner G, Torri G, and Rahn H. Respiratory mechanics during submersion and negative-pressure breathing. J Appl Physiol 21: 251-258, 1966[Free Full Text].

2.   Amis, TC, Hazel AJ, and Hughes JMB Effect of posture on inter-regional distribution of pulmonary ventilation in man. Respir Physiol 56: 145-167, 1984[ISI][Medline].

3.   Brunner, JX, Wolff G, Cumming G, and Langenstein H. Accurate measurement of N2 volumes during N2 washout requires dynamic adjustment of delay time. J Appl Physiol 59: 1008-1012, 1985[Abstract/Free Full Text].

4.   Bryan, AC, Milic-Emili J, and Pengelly D. Effect of gravity on the distribution of pulmonary ventilation. J Appl Physiol 21: 778-784, 1966[Free Full Text].

5.   Buono, AC. Effects of central vascular engorgement and immersion on various lung volumes. J Appl Physiol 54: 1094-1096, 1983[Abstract/Free Full Text].

6.   Cormier, Y, and Bêlanger J. Contribution of gas exchange to slope of phase III of the single-breath nitrogen test. J Appl Physiol 50: 1156-1160, 1981[Abstract/Free Full Text].

7.   Crawford, ABH, Makowska M, Kelly S, and Engel LA. Effect of breath holding on ventilation maldistribution during tidal breathing in normal subjects. J Appl Physiol 61: 2108-2115, 1986[Abstract/Free Full Text].

8.   Crawford, ABH, Makowska M, Paiva M, and Engel LA. Convection- and diffusion-dependent ventilation maldistribution in normal subjects. J Appl Physiol 59: 838-846, 1985[Abstract/Free Full Text].

9.   Dahlbäck, GO, Jönsson E, and Linér MH. Influence of hydrostatic compression of the chest and intrathoracic blood pooling on static lung mechanics during head-out immersion. Undersea Biomed Res 5: 71-85, 1978[ISI][Medline].

10.   Dutrieue, B, Lauzon AM, Verbanck S, Elliot AR, West JB, Paiva M, and Prisk GK. Helium and sulfur hexafluoride bolus washin in short-term microgravity. J Appl Physiol 86: 1594-1602, 1999[Abstract/Free Full Text].

11.   Elliot, AR, Prisk GK, Guy HJB, and West JB. Lung volumes during sustained microgravity on Spacelab SLS-1. J Appl Physiol 77: 2005-2014, 1994[Abstract/Free Full Text].

12.   Engel, LA. Intraregional gas mixing and distribution. In: Gas Mixing and Distribution in the Lung, , edited by Paiva M.. New York: Marcel Dekker, 1985, p. 287-358.

13.   Engel, LA. Dynamic distribution of gas flow. In: Handbook of Physiology. The Respiratory System. Mechanics of Breathing. Bethesda, MD: Am. Physiol. Soc, 1986, sect. 3, vol. III, pt. 2, chapt. 32, p. 575-593.

14.   Engel, LA, Grassino A, and Anthonisen NR. Demonstration of airway closure in man. J Appl Physiol 38: 1117-1125, 1975[Abstract/Free Full Text].

15.   Engel, LA, and Paiva M. Analysis of sequential filling and emptying of the lung. Respir Physiol 45: 309-321, 1981[ISI][Medline].

16.   Glaister, DH. Transient changes in arterial oxygen tension during positive (+Gz) acceleration in the dog. Aerospace Med 39: 54-62, 1968[Medline].

17.   Glaister, DH. Ventilation and mechanics of breathing. In: The Effects of Gravity and Acceleration on the Lung. Slough, UK: Technovision Services, 1970.

18.   Guy, HJB, Prisk GK, Elliot AR, Deutschman RAI, and West JB. Inhomogeneity of pulmonary ventilation during sustained microgravity as determined by single-breath washouts. J Appl Physiol 76: 1719-1729, 1994[Abstract/Free Full Text].

19.   Haefeli-Bleuer, B, and Weibel ER. Morphometry of the human pulmonary acinus. Anat Rec 220: 401-414, 1988[Medline].

20.   Henry, JP. The significance of the loss of blood volume into the limbs during pressure breathing. J Aviat Med 22: 31-38, 1951[Medline].

21.   Hong, SK, Cerretelli P, Cruz JC, and Rahn H. Mechanics of respiration during submersion in water. J Appl Physiol 27: 535-538, 1969[Free Full Text].

22.   Lauzon, AM, Prisk GK, Elliot AR, Verbanck S, Paiva M, and West JB. Paradoxical helium and sulfur hexafluoride single-breath washouts in short-term vs. sustained microgravity. J Appl Physiol 82: 859-865, 1997[Abstract/Free Full Text].

23.   Michels, DB, and West JB. Distribution of pulmonary ventilation and perfusion during short periods of weightlessness. J Appl Physiol 45: 987-998, 1978[Abstract/Free Full Text].

24.   Milic-Emili, J, Henderson JAM, Dolovich MB, Trop D, and Kaneko K. Regional distribution of inspired gas in the lung. J Appl Physiol 21: 749-759, 1966[Free Full Text].

25.   Modell, HI, and Baumgardner FW. Influence of the chest wall on regional intrapleural pressure during acceleration (+Gz) stress. Aviat Space Environ Med 55: 896-902, 1984[Medline].

26.   Olson, LE, and Rodarte JR. Regional differences in expansion in excised dog lung lobes. J Appl Physiol 57: 1710-1714, 1984[Abstract/Free Full Text].

27.   Paiva, M, and Engel LA. Model analysis of gas distribution within human lung acinus. J Appl Physiol 56: 418-425, 1984[Abstract/Free Full Text].

28.   Paiva, M, and Engel LA. Gas mixing in the lung periphery. In: Respiratory Physiology: An Analytical Approach, edited by Chang HK, and Paiva M.. New York: Marcel Dekker, 1989, p. 245-276.

29.   Paiva, M, Estenne M, and Engel LA. Lung volumes, chest wall configuration, and pattern of breathing in microgravity. J Appl Physiol 67: 1542-1550, 1989[Abstract/Free Full Text].

30.   Paiva, M, Verbanck S, and van Muylem A. Diffusion-dependent contribution to the slope of the alveolar plateau. Respir Physiol 72: 257-270, 1988[ISI][Medline].

31.   Prisk, GK, Elliot AR, Guy HJB, Kosonen JM, and West JB. Pulmonary gas exchange and its determinants during sustained microgravity on Spacelab SLS-1 and SLS-2. J Appl Physiol 79: 1290-1298, 1995[Abstract/Free Full Text].

32.   Prisk, GK, Lauzon AM, Elliott AR, Guy HJB, Paiva M, and West JB. Anomalous behavior of helium and sulfur hexafluoride during single-breath tests in sustained microgravity. J Appl Physiol 80: 1126-1132, 1996[Abstract/Free Full Text].

33.   Sjöstrand, T. Volume and distribution of blood and their significance in regulation of the circulation. Physiol Rev 33: 202-228, 1953[Free Full Text].

34.   Wilson, TA, Olson LE, and Rodarte JR. Effect of variable parenchymal expansion on gas mixing. J Appl Physiol 62: 634-639, 1987[Abstract/Free Full Text].

J APPL PHYSIOL 91(2):637-644
8750-7587/01 $5.00 Copyright © 2001 the American Physiological Society


This article has been cited by other articles:


Home page
 J. Appl. Physiol.Home page
S. Montmerle, P. Sundblad, and D. Linnarsson
Residual heterogeneity of intra- and interregional pulmonary perfusion in short-term microgravity
J Appl Physiol, June 1, 2005; 98(6): 2268 - 2277.
[Abstract] [Full Text] [PDF]

Home page
 J. Appl. Physiol.Home page
M. Rohdin, J. Petersson, M. Mure, R. W. Glenny, S. G. E. Lindahl, and D. Linnarsson
Distributions of lung ventilation and perfusion in prone and supine humans exposed to hypergravity
J Appl Physiol, August 1, 2004; 97(2): 675 - 682.
[Abstract] [Full Text] [PDF]

Home page
 J. Appl. Physiol.Home page
M. Rohdin, P. Sundblad, and D. Linnarsson
Effects of hypergravity on the distributions of lung ventilation and perfusion in sitting humans assessed with a simple two-step maneuver
J Appl Physiol, April 1, 2004; 96(4): 1470 - 1477.
[Abstract] [Full Text] [PDF]

Home page
 Eur Respir JHome page
P.M. Gustafsson, H.K. Ljungberg, and B. Kjellman
Peripheral airway involvement in asthma assessed by single-breath SF6 and He washout
Eur. Respir. J., June 1, 2003; 21(6): 1033 - 1039.
[Abstract] [Full Text] [PDF]

Home page
 J. Appl. Physiol.Home page
M. Gronkvist, E. Bergsten, O. Eiken, and P. M. Gustafsson
Inter- and intraregional ventilation inhomogeneity in hypergravity and after pressurization of an anti-G suit
J Appl Physiol, April 1, 2003; 94(4): 1353 - 1364.
[Abstract] [Full Text] [PDF]

Home page
 J. Appl. Physiol.Home page
M. Gronkvist, E. Bergsten, and P. M. Gustafsson
Effects of body posture and tidal volume on inter- and intraregional ventilation distribution in healthy men
J Appl Physiol, February 1, 2002; 92(2): 634 - 642.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF) Free
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via ISI Web of Science (7)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Gustafsson, P. M.
Right arrow Articles by Grönkvist, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Gustafsson, P. M.
Right arrow Articles by Grönkvist, M.

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Visit Other APS Journals Online