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1 Biomedical Physics Laboratory, Université Libre de Bruxelles, Brussels 1070, Belgium and 2 Department of Medicine, University of California, San Diego, La Jolla, California 92093-0931
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ABSTRACT |
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 TOP
 ABSTRACT
 INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
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We studied the ventilation-perfusion matching pattern in normal gravity (1 G) and short- and long-duration microgravity (µG) using the cardiogenic oscillations in the sulfur hexaflouride (SF6) and CO2 concentration signals during the phase III portion of vital capacity single-breath washout experiments. The signal power of the cardiogenic concentration variations was assessed by spectral analysis, and the phase angle between the oscillations of the two simultaneously expired gases was obtained through cross-correlation. For CO2, a significant reduction of cardiogenic power was observed in µG, with respect to 1 G, but the reduction was smaller and more variable in the case of SF6. A shift from an in-phase condition in 1 G to an out-of-phase condition was found for both short- and long-duration µG. We conclude that, although the distribution of ventilation and perfusion becomes more homogeneous in µG, significant inhomogeneities persist and that areas of high perfusion become associated with areas of relatively lower ventilation. In addition, these modifications seem to remain constant during long-term exposure to µG.
ventilation-perfusion ratio; cardiogenic oscillations; long-duration microgravity.
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INTRODUCTION |
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TOP
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
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THE REGIONAL
MISMATCH between ventilation and blood flow in the lung results
in the impairment of the gas exchange. Thus the measurement of the
distribution of ventilation and perfusion provides us with valuable
information about the efficiency of the human lung. The cardiogenic
oscillations observed in phase III of single-breath washout (SBW) tests
are a measure of the regional inhomogeneities in gas concentrations in
the lung. The measured concentration signals are the results of the
complex summation of the flow coming from different areas of the lung
that contain different concentrations of the inspired and resident
gases (1). The relative contribution of these different
regions to the total flow varies throughout a long expiration because
of the local mechanical action of the heart on the lung, which results
in the observed oscillatory pattern in the expired gas concentration
(2, 5). Comparison of the oscillations in the expirate of
CO2 and inspired insoluble inert gases [He, sulfur
hexafluoride (SF6), and Ar bolus] provides information on
the regional differences in the ventilation-perfusion ratio (
A/
) (4). The persistence of
cardiogenic oscillations in both soluble and insoluble gas expirates in
microgravity (µG) conditions shows that, although both ventilation
and perfusion become more uniform in weightlessness, significant
nongravitational inhomogeneities persist (3, 4, 6, 7, 9).
However, to date, there are no studies of long-term exposure to µG
(flight duration >2 wk) that address whether these residual
inhomogeneities change with time. This study was designed to address
that question.
In this paper, we present data from vital capacity (VC) SBW experiments
performed on board the Mir space station during the 179-day Euromir-95
mission. To make our analysis more robust, with respect to that used
previously (4), we developed a signal quality criterion
that determined the cardiogenic signal power with respect to its
sometimes noisy background. This technique provides us with an
objective basis for separating the signals from which phase relation is
to be determined from the signals in which noise makes the comparison
unreliable or questionable. We compared our improved technique
to a previous technique by reanalyzing the data reported by Lauzon et
al. (4), which was collected on a short-duration
spaceflight. The two-subject, long-duration study on Mir
confirms the findings of Lauzon et al. (4) regarding the
phase relationship between the concentrations of CO2 and
SF6 in the expirate. The data collected on Mir show no
significant changes in A/ caused by long-term
exposure to µG.
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MATERIALS AND METHODS |
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TOP
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
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Euromir-95
Experimental system. The measurement system consisted of a three-way pneumatic valve (Innovision), an ultrasonic flowmeter (Isler Bioengineering) placed between the mouth and the valve, a multigas analyzer (Brüel & Kjaer) that monitored O2, CO2, and SF6 concentrations continuously, and an electrocardiogram (ECG) monitor with R-wave detection implemented in hardware. The flowmeter was located just behind the mouthpiece. Gas was sampled by a capillary at the entrance of the flowmeter. The instrument dead space of the flowmeter and valve system was 181 ml. The gas flow, gas concentrations, and ECG were sampled at 100, 33, and 200 Hz, respectively. Functionally identical facilities were used inflight and on the ground for training and baseline data collection.
Experimental protocol. SBW maneuver was performed as follows: the seated subject breathed air through the mouthpiece for at least six normal tidal breaths and was then prompted to exhale to residual volume (RV). The valve was then switched to the port connected to a bag that contained a gas mixture of 25% O2, 1% SF6, and balance N2, and the subject inhaled to total lung capacity (TLC) at a constant flow of 0.5 l/s. A display provided feedback to the subject, allowing control of the flow. The subject then switched the valve to the expiratory port and was prompted to exhale to RV again, at a constant flow of 0.5 l/s.
Data collection. Two male subjects (M1, M2) were studied before, during, and after the 179-day spaceflight on the Mir station. The subjects' preflight ages were 37 and 39 yr, weights were 71 and 76 kg, and preflight height was 182 cm for both subjects. The subjects reported no respiratory symptoms and had normal spirometry results. The first preflight data collection session was held 173 or 170 days before launch for M1 and M2 respectively. Additional preflight data were collected 114, 73, and 31 days before launch. Postflight data collection was performed on days 1, 7, 12, and 118 after landing for both subjects. An additional postflight session was held on the postflight days 25 and 26 for M2 and M1 respectively. Inflight experiments were performed on flight days 6, 53, 82, 123, 132, 145, 164, and 172 for subject M1 and on flight days 5, 63, 83, 118, 142, and 170 for subject M2. Ambient pressure (means ± SD) equaled 1,010 ± 11 and 1,012 ± 35 mbar for the 1-G and µG experiments, respectively. The ambient O2 and CO2 concentrations inflight were, on average, 21 ± 0.8% and 0.96 ± 0.15%, respectively. The CO2 concentration inflight varied between 0.05% and 1.16% and exceeded 1% in 5 of 14 occasions.
Two SBW tests were performed during each experiment session. During the 5-min interval between the SBW tests, the subject performed other respiratory tests without any foreign gas mixture. This ensured a complete washout of the lungs before each test. Due to hardware calibration problems, we obtained, in total, 5 acceptable SBW maneuvers out of 8 preflight, 12 out of 16 in-flight, and 6 out of 10 postflight for subject M1. For subject M2 we obtained 7 out of 8 maneuvers preflight, 9 out of 12 inflight, and 9 out of 10 postflight.Data analysis.
The cardiogenic oscillation signal quality was ensured by requiring
that sufficient signal energy be present at a given heart beat
frequency (fHR). For this purpose, the ECG and the gas
concentration signals of the phase III portion of the SBW were analyzed
spectrally by means of a fast Fourier transform with a Hanning
windowing function. Gas concentration signals were detrended with a
third-order polynomial to ensure stationary position of the signal
before spectral analysis. We defined the normalized cardiogenic signal power (Pn) as the ratio of the spectral power density of
the gas concentration in the interval (fHR 
HWHM,
fHR + HWHM) to the power density in the interval (0, 1.5 fHR)
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(1) |
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(2) |
g1g2
the cross-correlation function,
g1g1 and
g2g2 are the auto-correlation
functions, and 
is the phase shift of the cross-correlation
function. The correlation function
gigj is given by
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(3) |
) nearest to the
zero phase shift ( = 0) and is expressed in degrees by mapping
a 360° phase shift to the mean heart rate periodicity. To ensure a
sufficient cardiogenic signal quality, this phase analysis was
performed only on those SBW tests for which, for both gases
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(4) |
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SLS-2
The experimental system, the performance of the maneuvers, the subjects, and the data-collection schedule for the SBW experiments are presented in detail in Refs. 4 and 7. Briefly, five subjects performed VC SBW maneuvers in which trace quantities of He and SF6 were present in the inspirate. Data were collected four times preflight, four times during the 14-day flight, and five times postflight. The experimental apparatus consisted of a bag-in-box system, a mouthpiece-rotary valve unit, a differential pressure-based flowmeter, and a magnetic-sector mass spectrometer. After a few normal breaths, the subject was prompted to exhale to RV, turn the rotary valve, inhale the test gas mixture to TLC at 0.5 l/s, and then exhale back to RV at the same flow rate. A display allowed the subject to control the flow. The subjects retained their assigned numbers from previous reports (4, 7).Statistical Analysis
For the short- (SLS-2) and long-duration (Euromir-95) µG experiments, a one-way ANOVA was performed (SPSS 6.1, SPSS, Chicago, IL) on a per subject basis, between the three categories (preflight, inflight, and postflight), with Scheffé's repeated measurement correction. Whenever this analysis yielded no significant difference between pre- and postflight values, the data were pooled. A two-way ANOVA was used to determine whether any interaction effects existed between the gravity level and the individual subjects. Finally, unpaired t-tests were performed between 1 G and µG data. In addition, the time dependence between early and late inflight measurements was tested by means of the nonparametric Kruskal-Wallis test. All results are expressed as means ± SE.| |
RESULTS |
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ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
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Signal Power Analysis
Figure 2 shows Pn at the cardiac frequency with pooled pre- and postflight data for the entire test sets from the long- and short-duration µG experiments. A significant reduction of the CO2 power in µG occurred in both studies. With all subjects pooled, the relative reduction in CO2 power, with respect to 1 G are67% for the
short-duration µG and 69% for the long-duration µG, with P < 0.001 for both. There were, however, large
intersubject variations. For the two subjects in the long-duration µG
study, the relative reductions of Pn in µG were 61 and
75%, whereas, for the 5 subjects in short-duration µG, this ranged
from 19 to 92%. The reduction in the power in the SF6
data is less marked [long-duration µG: 5%, not significant (NS);
short-duration µG: 42%, P < 0.01]. Here also,
large variations were observed between subjects (range: 78 to +29%
for the short-duration µG; 27 to +7% for the long-duration study).
No significant changes with time were observed for the Pn
of the two gases during either of the µG experiments.
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Test Quality
With respect to the flow variations within the tests, averaging the variation coefficient of the expired flow over all tests and all subjects yielded 16 ± 1% for the long-duration and 7 ± 1% for the short-duration µG experiment. Concerning the variability between tests, the variation coefficients of the mean flow were 11 and 8% for long- and short-duration µG, respectively. The variation coefficient for the mean flow between tests ranged from 7 to 8% for the different subjects in short-term µG and from 7 to 9% for the two long-term µG subjects. In addition, the variation coefficients of the individual subjects, averaged over all tests performed, ranged from 3 to 10% for the short-duration and from 13 to 18% for the long-duration experiment.Test Selection
Table 1 shows an overview of the rejected tests from the two experiments following the criterion of Eq. 4. For short-duration µG, ~10% of the 1 G tests and 25% of the µG tests were removed from the data set; however, for the long-duration exposure to µG, ~40% of the µG tests were rejected but none of those performed in 1 G were removed. Note that, in the latter experiment for each subject, there was one inflight experiment that passed the signal quality criterion but did not allow the unambiguous determination of the maximum of the cross-correlation function (Eq. 2) because the correlation function lacked periodicity or the maximum resembled a plateau. Hence, these tests were also excluded from the phase analysis.
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Phase Relationship
Figure 3 shows the phase difference between the cardiogenic oscillations of CO2 and SF6 for the long- and short-duration µG experiments. A double plot format is used, in which the results are plotted twice and spaced by 360° to obtain two distinct clusters: one for the out-of-phase (~90-270°) and one for the in-phase (~270-450°) measurements. For both experiments, no significant difference was observed between pre- and postflight measurements. Furthermore, two-way ANOVA did not reveal any significant interaction effect between the different subjects and the level of gravity. The cardiogenic oscillations for SF6 and CO2 are in phase in 1 G (overall average of pooled pre- and postflight values: 363 ± 5° for long-duration µG; 326 ± 5° for short-duration µG) and become out of phase in µG (overall average: 205 ± 21° for long-duration µG; 167 ± 28° for short-duration µG; P < 0.001 for both). There was no significant difference in phase shift between early and late inflight tests during long-duration exposure to µG as tested by Kruskal-Wallis nonparametric ANOVA (Table 2).
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DISCUSSION |
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TOP
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
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Cardiogenic Signal Power
A major problem with the study of ventilation-perfusion matching using cardiogenic oscillations during VC SBW maneuvers is the large intersubject variability of both the cardiogenic power in 1 G and its reduction when exposed to µG (Fig. 2). Several authors have observed important reductions in the size of the cardiogenic oscillations in going from 1 G to µG conditions (3, 6, 9). Guy et al. (3) observed a mean decrease of the cardiogenic signal amplitude of 56% for N2 (significant relative variations with respect to 1-G range from30 to 88%) and 76% for an Ar bolus
inhaled at RV (ranging from 70 to 87%) in comparable SBW tests
performed by the seven crew members of the 9-day SLS-1 Spacelab
mission. Our results are in good agreement with the observations of
Prisk et al. (7), who observed a ~50% decrease of
cardiogenic amplitude for CO2 during sustained µG. The
results of our short- and long-duration µG experiments are in
agreement with regard to the significant reduction of the oscillation
of CO2 and the much higher intersubject variability in the
SF6 signal.
The normalized cardiogenic power ratio, which we use here to estimate the cardiogenic oscillation signal strength has the advantage of being an objective measure that can easily be automated. It allows for the evaluation and comparison of signals that are not only sometimes very noisy but can also present a biphasic behavior (4). On the other hand, one should note that the actual value of Pn depends on the method used for the calculation of the spectrum of the gas concentrations in Eq. 1. The frequency resolution is inversely proportional to the duration of the signal. Thus windowing is commonly used to reduce the effects of the abrupt beginning and ending of the signal on the spectrum. Different windowing methods do not fundamentally alter the spectrum, but the exact position of the peaks and their widths are slightly different for different windowing functions. Nevertheless, Pn, as defined in Eq. 1, is a useful parameter when it comes to comparing the strength of cardiogenic oscillation signals between different experiments.
The necessary conditions for the observation of cardiogenic oscillations are twofold. 1) Concentration inhomogeneities exist between parallel units, and 2) the heart exerts a mechanical action on the lung units that periodically varies their relative contribution to the exhaled flow. The concentration inhomogeneities are due to ventilation differences for SF6 and ventilation and perfusion differences in the case of CO2. These conditions allow us to hypothesize about the changes with time of the cardiogenic mixing phenomenon during long-term exposure to µG. It is well known that ventilation and perfusion become more homogeneously distributed in weightless conditions (4, 6, 9), which will tend to reduce the cardiogenic oscillations. The 6-mo Euromir-95 mission gave us, for the first time, the opportunity to assess the long-term changes of these residual inhomogeneities beyond 2 wk of µG exposure and to investigate whether the absence of mechanical stresses could affect ventilation. Concerning the mechanical action of the heart, the stroke volume is known to remain fairly constant at elevated levels compared with preflight measurements on ground after a transition period in µG of approximately one week (Ref. 8 and Prisk, unpublished observations). An increase in stroke volume will tend to enhance the cardiogenic signal power. Hence, the observed decrease in cardiogenic oscillations amplitude would mean that this effect is counteracted by a relatively larger increase in ventilation and perfusion homogeneity. However, the actual orientation and impact of the mechanical action of the heart on the lungs is likely to change between 1-G and µG environments. The amplitude of this effect remains unknown and is not addressed by this work. Thus, with regard to the evolution with time during space flight, no modifications of the signal amplitude would be expected after the first week in µG. This is confirmed by our observation that Pn does not change significantly during the time course of the exposure to µG.
Test Quality
The quality of the SBW experiment depends on the capacity of the subjects to exhale at a constant rate. The flow at which the SBW maneuver is performed determines the relative contribution of the different lung regions to the mixing of the expired gases at a given instant. Hence, controlling the expired flow rate enables the comparison between experiments, assuming identical mechanical action of the heart. In both the short- and long-duration µG experiments, the repeatability of the SBW tests was largely satisfactory, thus allowing for valid comparison. In addition, intersubject variability remained relatively low, which allowed us to assume that the observed variability in power and phase of the cardiogenic oscillations are independent of subject performance.Phase Relationship
It is clearly observed that the CO2 and SF6 concentrations are in phase at 1 G and out of phase in µG (Fig. 3). This phase shift can be explained as follows. The gravitational model predicts that, under normal gravity, both SF6 and CO2 are distributed preferentially to the dependent zones of the lung. These areas have high ventilation and high perfusion, which explains the in-phase relationship between the cardiogenic oscillations of the two gases. The out-of-phase condition observed in µG means that areas with low ventilation, i.e., low SF6, are now associated with areas with higher perfusion than under normal gravity conditions. Hence, the regional distribution ofA/ has changed. This is consistent with
the findings of Lauzon et al. (4), who reported an average
phase shift between CO2 and He of 332 ± 6° in 1 G
and 263 ± 27° in short-duration µG. We have analyzed the
SF6 data from the same mission, which were reported to be
noisier than the He data (4), and obtained identical
results. Furthermore, our results indicate that these changes are
immediate on entering µG and remain constant during long-term
exposure (>5 mo) to µG.
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ACKNOWLEDGEMENTS |
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Y. Verbandt, M. Wantier, and G. K. Prisk acknowledge the support by the Belgian Federal Office for Scientific, Technical, and Cultural Affairs (OSTC) via the European Space Agency (ESA) PRODEX program under the contracts 12557/NL/WK(PU) and 13129/98/NL/VJ(IC). G. K. Prisk was supported by Lockheed Martin Subcontract G860600J67 and NASA Contract NAS9-19434.
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FOOTNOTES |
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Address for reprint requests and other correspondence: Y. Verbandt, Biomedical Physics Laboratory, Université Libre de Bruxelles, CP 613/3, 808, Route de Lennik, B-1070 Brussels, Belgium (E-mail: yverband{at}ulb.ac.be).
The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
Received 3 April 2000; accepted in final form 30 June 2000.
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REFERENCES |
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TOP
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
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, 1G; ×, µG.