Lung in Micro Gravity

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89:385-396, 2000.J Appl PhysiolG. Kim Prisk

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Physiology of a Microgravity Environment

Invited Review: Microgravity and the lung

G. KIM PRISK Department of Medicine, University of California, San Diego, La Jolla, California 92093

Prisk, G. Kim. Invited Review: Microgravity and the lung. J ApplPhysiol 89: 385 396, 2000.Although environmental physiologistsare readily able to alter many aspects of the environment, it is notpossible to remove the effects of gravity on Earth. During the pastdecade, a series of spaceflights were conducted in which comprehensivestudies of the lung in microgravity (weightlessness) were performed.Stroke volume increases on initial exposure to microgravity and thendecreases as circulating blood volume is reduced. Diffusing capacityincreases markedly, due to increases in both pulmonary capillary blood

volume and membrane diffusing capacity, likely due to more uniformpulmonary perfusion. Both ventilation and perfusion become more uni-form throughout the lung, although much residual inhomogeneity re-mains. Despite the improvement in the distribution of both ventilationand perfusion, the range of the ventilation-to-perfusion ratio seen duringa normal breath remains unaltered, possibly because of a spatial mis-match between ventilation and perfusion on a small scale. There areunexpected changes in the mixing of gas in the periphery of the lung, andevidence suggests that the intrinsic inhomogeneity of the lung exists ata scale of an acinus or a few acini. In addition, aerosol deposition in thealveolar region is unexpectedly high compared with existing models.

ventilation; perfusion; ventilation-perfusion ratio; lung volumes; diffus-ing capacity; gas exchange; aerosol deposition; aerosol dispersion; hyp-oxia; hypercapnia

THE LUNG IS AN UNUSUAL ORGAN in that it comprises littleactual tissue mass in a relatively large volume. It is anexpanded network of air spaces and blood vessels de-signed to bring gas and blood into very close proximityto each other to facilitate efficient gas exchange. As adirect consequence of this architecture, the lung ishighly compliant and is markedly deformed by its own

weight.Although there is little, if any, structural differencebetween the top and bottom of the normal human lung,there are marked functional differences caused by theeffects of gravity. For example, there are significantdifferences in regional lung volumes, ventilation, pa-renchymal stress, blood flow, ventilation-to-perfusionratio (VA/Q), and gas exchange (9, 42, 52, 93, 94, 95).

Numerous studies have examined the influence ofgravity on the lung, by using either postural change asthe alteration in gravity or hypergravity as a means ofincreasing the gravitational effect. However, data obtained in the absence of gravity have only recentlybecome available. This review summarizes the resultsof some of those studies.

MAKING PULMONARY FUNCTION MEASUREMENTS IN

MICROGRAVITY

There are only two practical methods of achievingmicrogravity suitable for human experimentation: parabolic flight in aircraft and spaceflight. Parabolic flighthas the advantage of being relatively accessible and (incomparison to spaceflight) inexpensive. However, iprovides only short periods of microgravity (2025 s)and these are usually sandwiched between periods ohypergravity because of the maneuver the aircrafmust fly. Although spaceflight provides sustained mi

Address for reprint requests and other correspondence: G. K.Prisk, Dept. of Medicine, Univ. of California, San Diego, 9500 Gil-man Drive, La Jolla, CA 920930931 (E-mail: [email protected]).

J Appl Physio89: 385396, 2000

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crogravity (1 wk to more than 1 yr at present), flightopportunities are infrequent at best.

Since 1983, the US Space Shuttle has, at times,carried the European-built Spacelab in the cargo bay.Spacelab provided a large increase in the habitable volume of the normally cramped Shuttle and gaveresearchers a normoxic, normobaric environment inwhich to conduct research. Space Shuttle flights are

limited to missions of short duration (the maximumcurrently is 17 days); therefore, only acute phases ofthe adaptation to microgravity can be studied. Mis-sions of longer duration have, to date, been limited tothe Mir space station and before that to Salyut andSkylab, although there have been few studies in thosesettings.

Both head-down tilt and water immersion have beenused as analogs of microgravity. However, these meth-ods do not adequately simulate microgravity in termsof lung function, and they are not discussed in thisreview. There are, however, reviews that may proveuseful for comparison purposes (e.g., see Refs. 32 and55).

PULMONARY BLOOD FLOW AND FLUID

REDISTRIBUTION

Total pulmonary blood flow and fluid distribution.The first direct measurements of pulmonary blood flowwere made during Spacelab Life Sciences-1 (SLS-1) in1991. Seven subjects were studied over the course of a9-day mission. Cardiac output rose by 35% abovepreflight standing levels 24 h after the onset of micro-gravity and then decreased during microgravity expo-sure. There was a slight bradycardia, and, as a result,stroke volume was increased by 6070% early in flightand also showed a subsequent decrease (Fig. 1) (66).

Similar results were obtained using an independenttechnique on SLS-1 and SLS-2 and showed an overall26% increase in cardiac output at rest in microgravity(77) and a 55% increase in cardiac stroke volumeSubsequent measurements on Spacelab D-2 (82) confirmed the SLS-1 measurements.

Echocardiographic measurements made duringSLS-1 (10) showed increases in cardiac dimensions and

stroke volume of a similar magnitude. Of particularinterest, however, is the fact that these increases occurred in the face of significant decreases in cardiacfilling pressures, inferred from central venous pressure(CVP). Measurements made on SLS-1 and SLS-2 (10and independently on D-2 (29) show convincingly thatcontrary to expectations, CVP falls in microgravityBecause the changes in CVP occur within seconds othe removal of gravity, it seems highly unlikely thatthere is any change in cardiac muscle performance perse. Thus the change implies that transmural pressuremust have increased, presumably due to a decrease inextracardiac pressure. The fact that lung volume actually decreases slightly on entry into microgravity (im

plying an overall increase in pleural pressure) suggeststhat local pressure changes must be considered whenconsidering cardiac performance. Similar changes inintravascular pressures have been seen in parabolicflight (45), although a clear understanding of the seem-ingly contradictory results is not yet available (97, 98)Recent observations (87) support the suggestion of adecrease in extra cardiac pressure during paraboliflight.

Measurements of pulmonary CO-diffusing capacity(DL

CO) and the membrane component (Dm) both show

increases in microgravity of25% (66), with no changein either during a 9-day flight. These changes likely

stem from a more uniform filling of the pulmonaryvasculature in microgravity with recruitment of capillaries near the apices that are unperfused in 1 G. Thepossibility of pulmonary edema formation in microgravity was suggested by Permutt (60); however, evidence suggests that this does not occur. If edema hadoccurred, a decrease in DL

COand Dm would have been

expected early in flight, with possible increases later asthe edema resolved. Pulmonary tissue volume, which issensitive to extravascular fluid in the lungs (61), wasunchanged after 24 h of microgravity and was 2025%lower after 9 days (82) despite increases in thoracicblood volume (4, 43, 56). These results are consistentwith observations of the low compliance of the pulmo

nary interstitium (53), which, in the presence of apressure fall (10), would be expected to result in agradual reduction in fluid in the pulmonary tissue.

Distribution of pulmonary perfusion. Gravity haslong been known to have a strong influence on thedistribution of pulmonary perfusion (94, 95). More re-cently, studies have shown that, at least in some species, nongravitational factors are also important (6, 3188, 92) and that there is also nongravitational inhomogeneity of pulmonary blood flow in human lungs (38).

There are no direct measurements of the distributionof pulmonary blood flow during spaceflight. Imaging

Fig. 1. Cardiac stroke volume during 9 days of exposure to micro-gravity (G). Data are expressed as percentage of preflight standing.#P 0.05 compared with preflight standing. P 0.05 comparedwith preflight supine. [From Prisk et al. (66).]

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was performed after parabolic flights in F-100 jets inwhich radioactively labeled microaggregated albuminwas injected into the subjects during the weightlessportion of the flight (79). These studies showed someincrease in apical blood flow in microgravity comparedwith that shown in the upright position in 1 G.

Because of the difficulties associated with radioac-tive imaging techniques in flight, an indirect technique

allowed inferences to be made about the distribution ofpulmonary blood flow (50). Subjects hyperventilatedfor 20 s, reducing the overall PCO2 in all regions of thelungs. They then rapidly inhaled to total lung capacity(TLC) and held their breath for 15 s. During thisbreath-hold period, CO2 evolved into the alveoli at arate proportional to the blood flow per unit alveolarvolume. Because the lung was at TLC, any interre-gional differences in lung volume were minimized;therefore, the CO2 level in a lung region became amarker of the perfusion of that region. At the end of thebreath-hold period, the subject exhaled in a controlledfashion to residual volume (RV). During the exhala-tion, markers of interregional inhomogeneity such ascardiogenic oscillations and a terminal fall in CO2 afterthe onset of airways closure provided indications of thedegree of inhomogeneity of perfusion.

In 1 G, there were prominent cardiogenic oscillationsand a marked fall in CO2 toward the end of exhalation(68). In supine in 1-G tests, the heights of both thecardiogenic oscillations and the terminal fall were de-creased to 60% of that seen standing (Fig. 2). Theseobservations are consistent with the known verticalgradient of pulmonary blood flow and its reduction inthe supine position.

In sustained microgravity, the cardiogenic oscillations persisted, whereas the terminal fall was absentBecause airway closure still occurs in microgravity (seePULMONARY VENTILATION, below), the absence of a terminal fall of CO2 means that blood flow in the regions oflung behind airways that close, and in the regions olung behind airways that remain open, must be similar. This is consistent with the removal of the top-to

bottom gradients in blood flow that are present in 1 Gand with the increase in DL

COand its components seen

in microgravity (66).The persistence of cardiogenic oscillations in micro

gravity, however, implies that there is persisting inhomogeneity of pulmonary blood flow. Although microgravity would be expected to abolish apicobasadifferences in perfusion, it would not necessarily affectother nongravitational interregional mechanisms of inhomogeneity (6, 38). Microgravity also would not necessarily affect the variability in lung compliance withinsmall regions of the lung (57), which may contribute todifferential gas flows from different areas of the lungduring the cardiac cycle. The residual inhomogeneitymust, however, be on a scale larger than the acinusbecause concentration differences on that scale wouldbe obliterated due to the fact that small differences inthe distance between different acini and the mouthwould result in cardiogenic oscillations being smearedout by the time the gas was expired and to diffusionamixing, which would reduce differences in CO2 between closely spaced regions.

PULMONARY VENTILATION

The inhomogeneity of pulmonary ventilation resultsfrom two major sources. The first is commonly recog-nized and is termed convective-dependent inhomogeneity (CDI). CDI results from two regions of the lunghaving different amounts of ventilation per unit lungvolume (specific ventilation) and may be gravitationaand nongravitational. The second is diffusion-convective-dependent inhomogeneity (DCDI). This is a complex interaction between the convective and diffusivetransport of gas in the branching structure of the lung(58, 86). Because it depends on the interaction betweenconvection and diffusion, DCDI is only operative whenthese two mechanisms are of a similar magnitude. Inhumans, DCDI is only operative at about the level othe first acinar generations. Thus DCDI can be thoughof as small-scale inhomogeneity, whereas CDI is nec

essarily observed at a larger scale (since if it werepresent within the acinus, diffusive transport wouldabolish the concentration gradients set up by CDI).

Convective inhomogeneity. Single-breath washouts(SBWs) have been performed several times in micro-gravity. The first was in parabolic flight: Michels andWest (50) showed that there were marked reductionsin the main markers of interregional inhomogeneitycardiogenic oscillation size, and the terminal rise innitrogen concentration following a vital capacity (VCinspiration of pure oxygen. Such reductions are consis-tent with a reduction or removal of top-to-bottom dif

Fig. 2. Relative size of cardiogenic oscillations in CO2 and height ofphase IV. Values are means SE; n 4 subjects. For purposes ofcomparison, height of phase IV (which is negative in 1 G) has beeninverted. Note that, in G, height of phase IV becomes dispropor-tionately small compared with that at 1 G standing and 1 G supine.*Significantly different (P 0.05) compared with standing. [FromPrisk et al. (68).]

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ferences in ventilation. However, Michels and Westshowed that some inhomogeneity persisted, based onthe continued presence of cardiogenic oscillations and aterminal rise. The question that could not be resolvedwas whether the preceding period of hypergravity nec-essary to fly the parabolic maneuver resulted in resid-ual inhomogeneities in the microgravity phase.

During SLS-1, VC SBW nitrogen tests were per-

formed on the seven-member crew (34). These testsalso included the inhalation at RV of a small argonbolus to provide information on airway closure. Theresults largely confirmed those from parabolic flight,with marked reductions in the height of the terminalrise in N2 and in cardiogenic oscillations but a clearpersistence nevertheless. This suggested a strong roleof gravity in CDI with considerable influence fromnongravitational factors. Airway closure measuredwith the argon bolus, often considered a gravitationalphenomenon, still occurred at a similar lung volume inmicrogravity in most subjects, although clearly thiswas not closure of the gravitationally dependent re-

gions of the lung seen in 1 G. The onset of airwayclosure occurred at the same absolute lung volume in 1G and in microgravity, suggesting that some unitsreach the point of zero elastic recoil at a similar abso-lute lung volume regardless of the gravitational distor-tion of the lung.

In the multiple-breath washout (MBW) technique,N2 is eliminated over a series of breaths. This is poten-tially advantageous because the breaths are muchsmaller and more closely approximate those of normalbreathing compared with the VC maneuvers used inthe single-breath tests. MBW tests performed duringSLS-1, analyzed in six different ways, showed fewsignificant changes between the data collected stand-

ing and those collected in microgravity (67). This sur-prising result led to the conclusion that the primarydeterminants of CDI during tidal breathing in theupright posture were not gravitational in origin. Sim-ilarly, analysis of the data collected during rebreathingtests performed on D-2 (83) showed that the degree ofgravity-independent inhomogeneity of specific ventila-tion was at least as large as the gravity-dependentinhomogeneity of specific ventilation in 1 G.

Diffusive inhomogeneity. The SBW performed inSLS-1 (34) also confirmed the previous observationmade in parabolic flight (50), namely, that phase IIIslope was only slightly reduced by the removal of grav-

ity. Although CDI in conjunction with asynchronousemptying had been shown to contribute to phase IIIslope, various studies (e.g., Ref. 18) had suggested thatonly about one quarter of the observed phase III slopein normal subjects was due to CDI. Other studies (15)showed that the continued exchange of respiratorygases in the lung made an additional 10% contribu-tion to phase III slope, leaving the bulk of the slopebeing due to DCDI effects. Consistent with these esti-mates, the observations in SLS-1 showed that phase IIIslope for N2 in microgravity was 75% of that seenstanding in 1 G (34).

Diffusive effects can be studied by performing washouts in which trace quantities of He and sulfurhexafluoride (SF6) are included in the test gas used forinspiration. Because of the wide difference in molecular weight (4 vs. 146) between these gases, He diffusesabout six times more readily than SF6. In 1 G, thisdifference in diffusivity results in the phase III slopefor SF6 being considerably steeper than that for He

There are two causes for this. The transport of themore diffusible He becomes dominated by diffusion at apoint in the airways more proximal (central) than doesthe less diffusible SF6, and the human acinus is moreasymmetric in the periphery (37). Second, the morerapid diffusion of He serves to abolish concentrationgradients established either by CDI or DCDI, flattening the He slope (86).

During D-2 and SLS-2, SBWs using He and SF6 wereperformed. In both cases, there was a flattening of thephase III slopes for both gases, but, surprisingly, theHe and SF6 slope became the same in microgravity (6984). When a breathhold was also performed, the phaseIII slope for SF6 actually became flatter than that for

He (Fig. 3). The only other known example of the SF6slope becoming flatter than the He slope was in heartlung transplant recipients undergoing acute rejectionepisodes. In that case, conformational changes near theentrance of the acinus, possibly as a result of acuteinflammation, steepened the He slope (81). Inflammation was clearly not the cause in microgravity, sincethe phase III slope difference had returned to preflight values within 6 10 h of landing. The results frommicrogravity suggest that a conformational change inthe acinus such as asymmetric narrowing of daughterairways at branch points, perhaps due to peribronchiacuffing, was responsible. Alternatively, changes in car

diogenic mixing may have altered the position and/orextent of the quasi-stationary concentration front developed by the interaction between convective and diffusive transport. However, no specific mechanismcould be identified. When the same tests were performed in the 25 s of microgravity available in parabolic flight, the phase III slope difference between SF6and He actually increased, as opposed to the decreaseseen in sustained microgravity (47). This suggests thatfluid shifts, which take longer than 25 s to occur, likelyplay a role. Because the changes all resulted fromdifferences in the behavior of the more diffusible He, itseems that the changes in peripheral gas mixing occurat the level of the entrance of the acinus, where DCDI

dictates the behavior of He.During SLS-2, MBWs using He and SF6 were alsoperformed (64). CDI in these near-tidal-volumebreaths was largely unaltered between 1 G and microgravity, in line with the previous MBW study (67). TheSF6 He slope difference was also reduced (althoughin these smaller volume breaths, not abolished), similar to that seen in the SBW study (69). The data werepartitioned into the effects of CDI and DCDI (17, 1885). This partitioning showed that for N2 and SF6, bothof which have relatively distal quasi-stationary diffusion fronts, there was little difference in the contribu

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tion of CDI to overall inhomogeneity between 1 G andmicrogravity. However, for He, with a more proximalfront, the CDI contribution was abolished in micro-gravity (Fig. 4). This suggests that the CDI seen topersist in microgravity (34, 67) must be located be-

tween units that are sufficiently close to each other, sothat diffusion of He, but not of N2 or SF6, is an efficientmeans of abolishing the concentration gradients it pro-duces (i.e., between acini or between groups of a fewacini). This is the first instance in which it was possibleto estimate the size of the structures responsible forthe inhomogeneity of ventilation in microgravity. Therecent parabolic flight study of inhaled gas boluses alsosuggests that airway closure in microgravity occurs invery close proximity to airways that remain open (23),again providing a similar scale for the intrinsic inho-mogeneity of the lung.

PULMONARY GAS EXCHANGE AND THE DISTRIBUTION

OF VA/Q

Measurements made during SLS-1 and SLS-2showed that oxygen consumption and CO2 productionwere unchanged by exposure to microgravity (63)Tidal volume decreased by 15%, and there was acompensatory increase in breathing frequency (9%)The increase in frequency did not completely compensate for the change in tidal volume, and total ventila-tion decreased by 7%. However, when the reductionin physiological dead space, which presumably resultsfrom the removal of areas of high VA/Q, was factored inalveolar ventilation remained unchanged in microgravity compared with that measured standing in 1 GThe selection of a different combination of tidal volumeand breathing frequency appears to result from theremoval of the weight of the abdominal contents andshoulder girdle, placing the inspiratory muscles in adifferent configuration. There was no evidence of significant changes in respiratory drive based on the absence of large changes in inspiratory time and mean

inspiratory flow.There have been no direct measurements of VA/Qdistribution in microgravity. No imaging techniqueshave been used in flight that would allow such measurements, and techniques such as the multiple inertgas elimination technique (89) are too complex andtime consuming for spaceflight at this time. Even suchindirect but invasive methods such as alveolar-arteriaoxygen gradient measurements have not been performed in microgravity. There is a brief report of adecrease in arterial saturation measured from arterialized capillary blood sample, (36), but this has notbeen confirmed.

During a controlled, slow exhalation from TLC to

RV, there is a slope to the CO2 expirogram, cardiogenioscillations, and a terminal fall, all of which are mark-ers of inhomogeneity of gas exchange. During the exhalation, the intrabreath respiratory exchange ratiocan be measured, and, by comparing this with a mathematical model of gas exchange in a comparable lung

Fig. 4. Contribution of convection-dependent inhomogeneity to thnormalized slope of phase III (S

CDI) of SF6, He, and N2 measured

during multiple-breath washouts. Filled bars, standing positionopen bars, G. [From Prisk et al. (64).]

Fig. 3. A: normalized phase III slopes of He (F) and SF6 () fromsubjects standing in 1 G and during sustained G. Note that,whereas all data collected in 1 G have significantly steeper slopes forsulfur hexafluoride (SF6) than for He, this difference is abolished inG and is actually reversed after a breath hold. B: same data as Aseparated into breath-hold and non-breath-hold conditions. * SF6slope significantly different from that of He, P 0.05. [From Lauzonet al. (47).]

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the deviation from a perfect lung can be determined(33). Thus the range in the intrabreath respiratoryexchange ratio can be converted to a range of VA/Q (96),and this has been shown to reflect the degree of VA/Qinequality in the lung (48, 72). The technique is indi-rect at best and relies on a comparison between ob-served behavior and (theoretical) ideal behavior of thelung. Other effects may also intrude, such as changes

in sequential emptying between different parallel re-gions, which might introduce changes into the expiro-grams even in the absence of a change in VA/Q distri-bution. Nevertheless, it is the only information on therange of VA/Q in the lung in microgravity available todate.

During SLS-1 and SLS-2, there were significant car-diogenic oscillations seen in the CO2 expirogram inmicrogravity. Their continuing presence is strong evi-dence for continued interregional differences in VA/Q inmicrogravity, since cardiogenic oscillations largely re-flect regional differences in gas concentration (28).These regional differences in this case result fromdifferences in gas exchange.

There was a marked reduction in the VA/Q rangeduring phase IV of a prolonged exhalation (Fig. 5),consistent with the idea that the top-to-bottom gradi-ent in VA/Q had been abolished in microgravity. Theresult is consistent with the observation that alveolardead space was reduced in microgravity because of areduction in the high VA/Q regions of the lung.

There was no change in the range of VA/Q betweenstanding and microgravity over phase III of the pro-longed expiration, the portion approximating the vol-ume range used during tidal breathing. This result wassurprising given the prior observations in which micro-

gravity resulted in a reduction in the topographicagradients of both ventilation (34) and perfusion (68). Itwould seem that the different behaviors seen between1 G and microgravity in phase III and phase IV of theexpiration point to a different basis for the inhomogeneity in VA/Q. It may be that gas exhaled during phaseIV (in 1 G) is more reflective of top-to-bottom gradientsin VA/Q, since, in 1 G, airway closure occurs predomi

nately in gravitationally dependent lung regions. However, during phase III, expired gas concentration differences may be more reflective of nongravitationainterregional differences in VA/Q. Certainly, the datasuggest that, before the onset of airway closure, theprincipal determinants of VA/Q inequality in normasubjects are not gravitational in origin, althoughwhether the primary cause is residual inhomogeneityof ventilation or perfusion remains unclear.

Lauzon et al. (46) examined the phase relationshipsbetween the cardiogenic oscillations in the expired gassignals measured during the single-breath tests performed on SLS-2. The phase relationship between CO2(a gas that is added to the alveolar space at a ratedependent on the VA/Q) and He (a gas added duringinspiration and dependent on ventilation) reversed between 1 G and microgravity. In 1 G, CO2 was in phasewith He (high CO2 was associated with high He)consistent with the gravitational model in which highventilation (the bases of the lungs) is associated withlow VA/Q (resulting in high CO2, also in the bases of thelungs). However, in microgravity, this phase relationship was reversed, and high ventilation was now associated with high VA/Q. This suggests that, in microgravity, areas of high ventilation are associated withareas of low perfusion and vice versa. Although othernongravitational gradients in blood flow are present in

the lung (6, 31, 38), the phase reversal seen between 1G and microgravity provides direct evidence of a role ogravity in the distribution of VA/Q in the normal human lung. It was hypothesized that, although the topographic gradients in both ventilation and perfusionmay be reduced in microgravity, the lack of spatiacorrelation between ventilation and perfusion resultsin a wider distribution of VA/Q than might otherwise beexpected.

LUNG VOLUMES AND PULMONARY MECHANICS

Vital capacity. The first study of lung volumes inmicrogravity was performed in Skylab in the early

1970s (75), with VC showing an 10% decrease. However, ground controls that used the same hypobariatmosphere also showed a 35% reduction, confounding the spaceflight results (74). Michels and West (50showed no consistent differences in VC in microgravityduring parabolic flight, except an increase was notedwhen the initial push to RV was during microgravityand the remainder of the inspiration occurred in 1 GThey suggested that this might be due to a lower RV inmicrogravity due to an increase in intrathoracic bloodvolume. Radiographic measurements also performedin parabolic flight (49) showed a nonsignificant de

Fig. 5. Range of ventilation-perfusion ratio (VA/Q) seen over phaseIII and phase IV of prolonged exhalations in 8 subjects studied

standing (vertically lined bars), supine (horizontally lined bars), andin G (open bars). Values are means SE. Significantly different(P 0.05) compared with *standing and supine. [From Prisk et al.(63).]

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crease in apical-to-basal height and an increase in lungwidth. Paiva et al. (59) showed an8% reduction in VCduring microgravity compared with during 1 G. Forced vital capacity (FVC) measured in parabolic flight wasreduced by a small amount (100200 ml) (35). Thisresult contradicted that of a previous study of FVC inparabolic flight (30), but the difference appears to bethe failure to account for a falling cabin pressure dur-ing the microgravity phase of the flight in the earlierstudy.

During the SLS-1, VC was measured in seven sub-jects over the course of a 9-day flight (26). After 24 hin microgravity, VC was reduced by 5% comparedwith that standing in 1 G. By 72 h, the reduction hadbeen abolished, and values later in flight were notdifferent from control values (Fig. 6). Similar resultswere seen in FVC (25). The suggestion is that an earlyinflight increase in intrathoracic blood volume is re-sponsible, with a subsequent increase in VC as plasmavolume is reduced (3).

Functional residual capacity. Agostoni and Mead (2)predicted that microgravity would reduce functionalresidual capacity (FRC) by 10%. This was based on acranial shift of the diaphragm and abdominal contents

as gravity was removed (an effect that would decreaseFRC), an outward movement of the rib cage as theweight of the abdomen was removed, and an upwardmovement of the shoulder girdle (effects that wouldincrease FRC). Their prediction was largely confirmedby measurements performed during SLS-1 (26), inwhich FRC decreased by 15% in microgravity com-pared with that shown in standing subjects in 1 G butwas higher than that measured supine. These resultshave subsequently been confirmed by measurementsin other flights (82). Results from short periods ofmicrogravity in parabolic flight are consistent with

orbital studies, which showed a reduction in FRC of400 ml in microgravity compared with 1 G in seatedsubjects (59).

Residual volume. RV is generally quite resistant tochange. Transitions between upright and supine positions (1, 26, 80) and water immersion (11, 12, 73resulted in no significant decrease in RV. Similarlycentral vascular engorgement produced by G-suit in

flation does not reduce RV (11).In sustained microgravity, RV was shown to de

crease by 18% (310 ml) compared with that shown instanding subjects and was also significantly below thatmeasured in supine subjects (by220 ml) (26). A likelyexplanation is that, in microgravity, the large, apicobasal gradients in regional lung volume present in 1 Gare abolished (Fig. 7). In 1 G, when lung volume isreduced below FRC, airway closure begins in the moregravitationally dependent lung regions (because of distortion of the lung by its own weight), and this airwayclosure progresses up the lung until RV is reached (51)Thus the regional RV of basal lung units is dependenton airway closure, whereas the regional RV of apica

lung units is dependent on the balance of local staticforces. The result is a large difference in regional RVbetween the top and bottom of the lung in 1 G. Inmicrogravity, however, the apicobasal gradients in regional lung volume due to gravity are abolished. Theresult is that regional volume of lung units is muchmore uniform, and no region reaches its trapped gasvolume, resulting in an overall reduction in the RV ofthe lung (Fig. 7).

Forced expirations. Castile et al. (14) demonstratedthat postural changes altered the position and magnitude of the sudden changes in flow that characterize anindividuals maximum expiratory flow volume (MEFV

curve. These changes were consistent with wave speedtheory (22) in which changes in local airway stressescould alter the location of airway choke points. Inparabolic flight, there was a reduction in FVC and, athigh lung volumes, a reduction in the lung volume atwhich a given expiratory flow occurred in microgravity(35). These effects were consistent with an increase inintrathoracic blood volume, which would engorge thelung with blood and increase elastic recoil. At low lungvolumes, there was a scooping out of the MEFV curvesimilar to that seen in recumbency (14) and immersion(62) attributed to vascular engorgement.

In an orbital study that eliminated the periods ohypergravity preceding microgravity, Elliott et al. (25

found an early inflight reduction in FVC that disappeared by the fourth day in microgravity. In additionthe reduction in lung volume at which a given expiratory flow occurred was seen in the early flight data, butthis also disappeared later in flight, suggesting thatintrathoracic blood volume increases may have beenresponsible. However, at low lung volumes, there wereno discernible changes in the shape of the MEFV curveas were seen in parabolic flight.

Peak expiratory flow was significantly reduced earlyin flight but was back to control values after 9 days omicrogravity. These reductions were largely in the

Fig. 6. Inspiratory and expiratory vital capacities (IVC and EVC) for4 payload crew members of Spacelab Life Sciences-1. Vital capacityon flight day 2 (FD-2) was intermediate between standing and supinevalues and was reduced compared with flight days 4 (FD-4) and 9(FD-9). Values are means SE *Significantly different from stand-ing (P 0.05). [From Elliott et al. (26).]

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absence of parallel changes in lung volumes (e.g.,FVC), suggesting that the change was not simply aconsequence of scaling (as was seen supine). It wassuggested that the lack of a firm platform to pushagainst during the maneuver compromised the abilityof the subjects to generate maximum flows, with therecovery being due to improved subject performance asthey adapted to operating in a microgravity environ-ment.

Shape and movement of chest wall. In parabolicflight, microgravity caused an inward displacement ofthe abdominal wall, thus elevating the diaphragm andreducing lung volume (59). There was no correspondingchange in the rib cage, consistent with the radio-graphic observations (49). The results are consistentwith an increase in abdominal wall compliance, whichwas confirmed by Edyvean et al. (24) who showed anincrease in the abdominal contribution to tidal volumefrom 33% in 1 G to 51% in microgravity. By measuringgastric pressures, they demonstrated that abdominalcompliance increased from 43 to 70 ml/cmH2O between1 G and microgravity. Importantly, their data led themto suggest that there may be small, residual pleuralpressure gradients present in microgravity as a result

of shape changes in the chest wall, which may result insome residual inhomogeneity of ventilation.In spaceflight, the measurements have been limited

to noninvasive studies of pulmonary mechanics. In theD-2 and Euromir-95 studies (91), the abdominal con-tribution to tidal volume was seen to increase from 31to 58%, consistent with the results from parabolicflight.

CONTROL OF VENTILATION

Hypoxic response. During the Neurolab mission, thehypoxic ventilatory response was measured using an

isocapnic rebreathing technique (71). In microgravitythe slope of the increase in ventilation with decreasingarterial oxygen saturation was only about one-half thatmeasured when the subjects were standing (Fig. 8)Furthermore, this reduction was unchanged for theduration of the 16-day mission (65). The reduction wasalmost identical to that seen when the hypoxic ventilatory response was measured in supine subjects. Somestudies reported changes in hypoxic response in humans (76, 78, 99) and showed a substantial reductionin hypoxic response in the supine position comparedwith that in the upright position, although this is notwell known. This is probably because, in both microgravity and in the supine position, there is a substan

Fig. 7. A theoretical model of the lung at residual volume (RV) during 1-G conditions and in G. At RV, alveolarsize increases from base of lung to apex in 1 G and is uniform in G. If area 2 is less than area 1, total sum ofalveolar volumes may be less at G than at 1 G (depending on shape of chest wall). Graph of distribution of alveolarsize at RV (A) has been modified from Ref. 52. TLCr, regional total lung capacity. B and C: regional alveolar

volumes at different vertical distances during 1 G and G, respectively. [From Elliott et al. (26).]

Fig. 8. Slope of the hypoxic ventilatory response (HVR) measuredstanding (vertically striped bars) and supine (horizontally stripedbars) in 1 G and in G (open bars). HVR is approximately halved inG and supine. SaO2, arterial O2 saturation. Open brackets, P 0.05between adjacent bars. * P 0.05 compared with preflight standing[From Prisk et al. (65).]

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tial increase in blood pressure at the level of the carotidbodies because of the removal of the hydrostatic pres-sure difference between the heart and neck. In cats, thearterial chemoreceptors respond markedly to changesin blood pressure when they are hypoxic, becoming lessactive as blood pressure increases, but no such re-sponse is seen when conditions are hyperoxic (44).Similar observations made in dogs suggest that the

pathway for the changes in the hypoxic response iscentral, as an isolated alteration in carotid distendingpressure on one side of the animal results in changes inchemoreceptor output on the contralateral side (39,40). These studies provide an explanation of why thereis a reduction in the hypoxic response both in micro-gravity and supine, in the absence of changes in thepattern of ventilation breathing air (63) and of changesin the inspiratory occlusion pressures during airbreathing (65).

Hypercapnic response. In sharp contrast to the ven-tilatory response to hypoxia, microgravity resulted inno overall change in the ventilatory response to in-haled CO2 (65), measured using a rebreathing tech-nique (70). Results collected during an earlier flightalso failed to show any change in the ventilatory re-sponse to CO2 (65). Similarly, there was no change inthe response for supine subjects, consistent with pre-vious studies on the ground (78, 99). However, therewas an indication that the slope of the response steep-ened somewhat in both microgravity and supine sub-jects and that this was accompanied by a concomitantincrease in the PCO2 at a calculated ventilation of zero(a steeping and shift to the right of the response).There was also a small increase in the resting end-tidalPCO2 of the subjects measured during quiet breathingfrom 36 to 39 Torr (similar to that between standing

and supine of 3641 Torr), raising the possibility of ashift in the set point of the PCO2. Measurements madein an environmental chamber study in which the PCO2was elevated to 1.2% (8.6 Torr) also showed an earlyincrease in the set point (27) that gradually abatedover the 21 days of that study. However, there were nosignificant alterations when the environmental PCO2was controlled at 5.0 Torr. In the case of Neurolab,environmental PCO2 averaged only 2.3 Torr, a levelbelow that in the chamber studies, and it remainsunclear whether the ambient CO2 in the spacecraft isresponsible for the small changes seen in the CO2response.

INHALED AEROSOLS

Long-term spaceflight represents a situation inwhich aerosol deposition may be an important healthconsideration. In the spacecraft environment, the po-tential for significant airborne particle loads is highbecause the environment is closed and no sedimenta-tion occurs. Fires aboard the spacecraft, like thatwhich occurred on the Mir space station in 1997 (13),also produce large amounts of airborne particles. Sim-ilarly, microgravity provides for potentially high parti-cle concentrations in the airways because particles

that normally sediment will not be removed from theairways, leaving them potentially available for transport to the alveolar regions.

There have been no studies of aerosol deposition inthe human lung during spaceflight. However, Hoffmanand Billingham (41) studied the deposition of 2.0-mparticles during parabolic flights. They saw an almostlinear increase in deposition with G level over the

range 02 G. They showed a lower deposition than thatsuggested by Beekmans (7, 8) who had predicted a

Fig. 9. Comparison between experimental data of aerosol deposition(DE) in short periods of microgravity and numerical data obtainedwithin a 1-dimensional model (see Ref. 18a). AC: G, 1 G, and 1.6G, respectively. For each particle size, left bar of each pair representexperimental value, and right bar of each pair represents numerica value with contribution of each mechanism of deposition. Solid segments, deposition by diffusion; hatched segments, deposition bysedimentation; open segments, deposition by impaction. [From Darquenne et al. (19).]

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reduction in total deposition but an increase in depo-sition in the alveolar region in microgravity due togreater penetration of the particles into the lung. Muir(54) made similar predictions.

In retrospect, it appears that the results of Hoffmanand Billingham (41) were because of their choice ofparticle size (2.0 m). Darquenne et al. (19) studied thetotal deposition of 0.5-, 1-, 2-, and 3-m particles in a

series of parabolic flights. For measurements made in 1or 1.6 G, the results correlated very closely with one-dimensional model predictions, with a tendency for themodels to slightly overestimate total deposition. How-ever, in microgravity, total deposition significantly ex-ceeded predictions in all particles below 3 m in size.The effect was greatest for 1-m particles, for whichtotal deposition in microgravity was more than twicethat predicted by existing models (18a) (Fig. 9). Be-cause, for 0.5- and 1-m particles, deposition by impac-tion is negligible and because in microgravity there isno sedimentation, only diffusion is apparently left toaccount for the deposition. The conclusion drawn wasthat some form of enhanced diffusion, likely due tononreversibilities of flow in the branching airwaystructure, must be playing a role. Importantly, therewas nothing to suggest that this process was exclu-sively related to microgravity, and it is likely that thehypothesized effect was likely operating in 1 G as well.

Subsequently, Darquenne et al. (20) performed aseries of bolus deposition and dispersion studies in 0, 1,and 1.6 G. They found a strong dependence of deposi-tion on both gravity and on penetration volume. Im-portantly, dispersion continued to increase with pene-tration volume in microgravity, showing that gravity isnot the only mechanism responsible for dispersion inthe human lung. It seems likely that the previously

hypothesized nonreversibility of flow plays a signifi-cant role in this process.Aerosols also play a useful role in the study of con-

vective mixing in the lung, especially in microgravity,in which there is no sedimentation. Because the intrin-sic motion of the particles is so small, they behave as anondiffusing gas. Recent studies by Darquenne et al.(21) clearly show that convective ventilatory inhomo-geneity increases toward the periphery of the lung andthat these inhomogeneities persist in the absence ofgravity.

FUTURE DIRECTIONS

After the completion of the Neurolab flight in 1998,the National Aeronautics and Space Administrationmothballed the highly successful Spacelab system. In August of 1999, the Russian Mir space station wasabandoned after more than a decade of continuoushabitation. The promise for future spaceflight researchlies primarily with the International Space Station(ISS), but, until that facility is fully operational, whichwill likely not be before 2004, there are likely to be fewopportunities for pulmonary function studies in space.These opportunities will exist on some SpaceHabflights planned to occur irregularly until the ISS is

fully operational and on some limited studies on thefledgling ISS. One series of experiments planned forthe early stages of the ISS will study the effects oextravehicular activity (EVA, space walk) on the lungThe protective suits used during EVA operate at a verylow pressure (30 kPa) to enable astronaut mobilityAs a consequence, EVA carries with it the risk of gasbubble formation in the venous circulation and possible

decompression sickness (90). As these bubbles formmicroemboli in the lung, they disrupt the distributionof VA/Q and can be detected using the test of intra-breath respiratory exchange ratio (16).

Some might conclude that all that has been done inthis area of research is sufficient. Certainly, it is truethat, unlike some areas of physiology (such as bone andmuscle metabolism), there is little to suggest thatchanges in pulmonary function as a result of microgravity will limit the presence of humans in spaceHowever, we simply do not know what happens to thelung when gravity is removed for a long period of timeIn addition, microgravity provides a valuable tool tostudy the effects of gravity on the lung itself and on thebehavior of material within the lung (e.g., inhaledparticles), and the lung provides a convenient means ofmonitoring cardiac function. A Pulmonary FunctionSystem, part of the Human Research Facility for theISS, is under development, which may provide a meansof continuing the study of the effects of gravity on thelung.

REFERENCES

1. Agostoni E, Gurtner G, Torri G, and Rahn H. Respiratorymechanics during submersion and negative-pressure breathingJ Appl Physiol 21: 251258, 1966.

2. Agostoni E and Mead J. Statics of the respiratory system. In

Handbook of Physiology. Respiration. Washington, DC: AmPhysiol. Soc., 1964, sect. 3, vol. I, chapt. 13, p. 387428.3. Alfrey CP, Udden MM, Leach-Huntoon C, Driscoll T, and

Pickett MH. Control of red blood cell mass in spaceflight. J AppPhysiol 81: 98104, 1996.

4. Baisch FJ. Fluid distribution in man in space and effect of lowebody negative pressure treatment. Clin Investig 71: 6906991993.

6. Beck KC and Rehder K. Differences in regional vasculaconductances in isolated dog lung. J Appl Physiol 61: 5305381986.

7. Beekmans JM. The deposition of aerosols in the respiratorytract. I. Mathematical analysis and comparison with experimental data. Can J Physiol Pharmacol 43: 157172, 1965.

8. Beekmans JM.Alveolar deposition of aerosols on the moon andin outer space. Nature 211: 208, 1966.

9. Bryan AC, Milic-Emili J, and Pengelly D. Effect of gravity on

the distribution of pulmonary ventilation. J Appl Physiol 21778784, 1966.

10. Buckey, JC Jr, Gaffney FA, Lane LD, Levine BD, Watenpaugh DE, Wright SJ, Yancy CW Jr, Meyer DM, andBlomqvist CG. Central venous pressure in space. J AppPhysiol 81: 1925, 1996.

11. Buono MJ. Effect of central vascular engorgement and immersion of various lung volumes. J Appl Physiol 54: 109410961983.

12. Burki NK. Effects of immersion to water and changes in intrathoracic blood volume on lung function in man. Clin Sci MoMed 51: 303311, 1976.

13. Burrough B.Dragonfly: NASA and the Crisis Aboard Mir. New York: Harper-Collins, 1998.

394 INVITED REVIEW


12/13

14. Castile R, Mead J, Jackson A, Wohl ME, and Stokes D.Effects of posture and on flow-volume curve configuration innormal humans. J Appl Physiol 53: 11751183, 1982.

15. Cormier Y and Belanger J. Quantification of the effect of gasexchange on the slope of phase III. Bull Eur Physiopath Respir19: 1316, 1983.

16. Cotes JE. Lung Function: Assessment and Application in Med-icine (5th ed.). Oxford, UK: Blackwell, 1993.

17. Crawford ABH, Makowska M, and Engel LA. Effect of atro-pine on static mechanical properties of the lung and ventilation

distribution. J Appl Physiol 63: 22782285, 1987.18. Crawford ABH, Makowska M, Paiva M, and Engel LA.

Convection- and diffusion-dependent ventilation maldistributionin normal subjects. J Appl Physiol 59: 838846, 1985.

18a.Darquenne C and Paiva M. One-dimensional simulation ofaerosol transport and deposition in the human lung. J ApplPhysiol 77: 28892898, 1994.

19. Darquenne C, Paiva M, West JB, and Prisk GK. Effect ofmicrogravity and hypergravity on deposition of 0.5- to 3-m-diameter aerosol in the human lung. J Appl Physiol 83: 20292036, 1997.

20. Darquenne C, West JB, and Prisk GK. Deposition and dis-persion of 1-m aerosol boluses in the human lung: effect ofmicro- and hypergravity. J Appl Physiol 85: 12521259, 1998.

21. Darquenne C, West JB, and Prisk GK. Dispersion of 0.5- to2-m aerosol in G and hypergravity as a probe of convective

inhomogeneity in the lung. J Appl Physiol 86: 14021409, 1999.22. Dawson SV and Elliott EA. Wave-speed limitation on expira-

tory flow: a unifying concept. J Appl Physiol 43: 498515, 1977.23. Dutrieue B, Lauzon A-M, Verbanck S, Elliott AR, West JB,

Paiva M, and Prisk GK. Helium and sulfur hexafluoride boluswashin in short-term microgravity. J Appl Physiol 86: 15941602, 1999.

24. Edyvean J, Estenne M, Paiva M, and Engel LA. Lung andchest wall mechanics in microgravity. J Appl Physiol 71: 19561966, 1991.

25. Elliott AR, Prisk GK, Guy HJB, Kosonen JM, and West JB.Forced expirations and maximum expiratory flow-volume curvesduring sustained microgravity on SLS-1. J Appl Physiol 81:3343, 1996.

26. Elliott AR, Prisk GK, Guy HJB, and West JB. Lung volumesduring sustained microgravity on spacelab SLS-1. J Appl Physiol77: 20052014, 1994.

27. Elliott AR, Prisk GK, Schollman C, and Hoffman U. Parttwo: hypercapnic ventilatory response in humans before, duringand after 23 days of low level CO2 exposure. Aviat Space EnvironMed 69: 391396, 1998.

28. Engel LA. Dynamic distribution of gas flow. In: Handbook of Physiology. The Respiratory System. Mechanisms of Breathing.Bethesda, MD: Am. Physiol. Soc., 1986, sect. III, pt. 2, chapt. 32,p. 575593.

29. Foldager N, Andersen TA, Jessen FB, Ellegaard P, Stadea-ger C, Videbaek R, and Norsk P. Central venous pressure inhumans during microgravity. J Appl Physiol 81: 408412, 1996.

30. Foley MF and Tomashefski JF. Pulmonary function duringzero-gravity maneuvers. Aerospace Med 40: 655657, 1969.

31. Glenny RW and Robertson HT. Fractal properties of pulmo-nary blood flow: characterization of spatial heterogeneity. J ApplPhysiol 69: 532545, 1990.

32. Greenleaf JE. Physiological responses to prolonged bed restand fluid immersion in humans. J Appl Physiol 57: 619633,1984.

33. Guy HJ, Gaines RA, Hill PM, Wagner PD, and West JB.Computerized noninvasive tests of lung function. A flexible ap-proach using mass spectrometry. Am Rev Respir Dis 113: 737744, 1976.

34. Guy HJB, Prisk GK, Elliott AR, Deutschman RA III, andWest JB. Inhomogeneity of pulmonary ventilation during sus-tained microgravity as determined by single-breath washouts.J Appl Physiol 76: 17191729, 1994.

35. Guy HJB, Prisk GK, Elliott AR, and West JB. Maximumexpiratory flow-volume curves during short periods of micrograv-ity. J Appl Physiol 70: 25872596, 1991.

36. Haase H, Baranov VM, Asyamolova NM, Polyakov VVAvan Yan YG, Dannenberg R, Jarsumbeck B, and Konig JFirst results of PO2 examinations in the capillary blood of cosmonauts during a long-term flight in the space station MIR.Proc. 41st Congr. Int. Astronaut. Fed. Dresden Germany 1990. p14.

37. Haefeli-Bleuer B and Weibel ER. Morphometry of the humanpulmonary acinus. Anat Rec 220: 401414, 1988.

38. Hakim TS, Lisbona R, and Dean GW. Gravity-independeninequality of pulmonary blood flow in humans. J Appl Physio63: 11141121, 1987.

39. Heistad D, Abboud FM, Mark AL, and Schmid PG. Interaction of baroreceptor and chemoreceptor reflexes. J Clin Invest 5312261236, 1974.

40. Heistad D, Abboud FM, Mark AL, and Schmid PG. Effect obaroreceptor activity on ventilatory response to chemoreceptostimulation. J Appl Physiol 39: 411416, 1975.

41. Hoffman RA and Billingham J. Effect of altered G levels ondeposition of particulates in the human respiratory tract. J AppPhysiol 38: 955960, 1975.

42. Kaneko K, Milic-Emili J, Dolovich MB, Dawson A, andBates DV. Rational distribution of ventilation and perfusion asa function of body position. J Appl Physiol 21: 767777, 1966.

43. Kirsch KA, Baartz FJ, Gunga HC, and Rocker L. Fluidshifts into and out of superficial tissues under microgravity andterrestrial conditions. Clin Investig 71: 687689, 1993.

44. Lahiri S. Role of arterial O2 flow in peripheral chemoreceptoexcitation. Fed Proc 39: 26482652, 1980.

45. Latham RD, Fenton JW, Vernalis MN, Gaffney FA, andCrisman RD. Central circulatory hemodynamics in non humanprimates during microgravity induced by parabolic flight. AdvSpace Res 14: 349358, 1994.

46. Lauzon A-M, Elliott AR, Paiva M, West JB, and Prisk GKCardiogenic oscillation phase relationships during single-breathtests performed in microgravity. J Appl Physiol 84: 6616681998.

47. Lauzon A-M, Prisk GK, Elliott AR, Verbanck S, Paiva Mand West JB. Paradoxical helium and sulfur hexafluoride single-breath washouts in short-term vs. sustained microgravityJ Appl Physiol 82: 859865, 1997.

48. Meade F, Pearl N, and Saunders MJ. Distribution of lungfunction (VA/Q) in normal subjects deduced from changes in

alveolar gas tensions during expiration. Scand J Respir Dis 48354365, 1967.

49. Michels DB, Friedman PJ, and West JB. Radiographic comparison of human lung shape during normal gravity and weightlessness. J Appl Physiol 47: 851857, 1979.

50. Michels DB and West JB. Distribution of pulmonary ventilation and perfusion during short periods of weightlessness. J AppPhysiol 45: 987998, 1978.

51. Milic-Emili J. Static distribution of lung volumes. In: Handbook of Physiology. The Respiratory System. Mechanics oBreathing. Bethesda, MD. Am. Physiol. Soc., 1986, sect. 3, volIII, pt. 2, chapt. 31, p. 561574.

52. Milic-Emili J, Henderson JAM, Dolovich MB, Trop D, andKaneko K. Regional distribution of inspired gas in the lungJ Appl Physiol 21: 749759, 1966.

53. Miserocchi G, Negrini D, Del Fabbro M, and Venturoli D

Pulmonary interstitial pressure in intact in situ lung: transitionto interstitial edema. J Appl Physiol 74: 11711177, 1993.

54. Muir DCF. Influence of gravitational changes on the depositionof aerosols in the lungs of man. Aerosp Med 159161, 1967.

55. Nicogossian A. Microgravity simulations and analogues. In Space Physiology and Medicine, edited by Nicogossian AEHuntoon CL, and Pool SL. Philadelphia, PA: Lea & Febiger1994, p. 363371.

56. Norsk P and Epstein M. Manned space flight and the kidneyAm J Nephrol 11: 8197, 1991.

57. Olson LE and Rodarte JR. Regional differences in expansionin excised dog lung lobes. J Appl Physiol 57: 17101714, 1984.

58. Paiva M and Engel LA. The anatomical basis for the slopingN2 alveolar plateau. Respir Physiol 44: 325337, 1981.

395INVITED REVIEW


13/13

59. Paiva M, Estenne M, and Engel LA. Lung volumes, chest wallconfiguration, and pattern of breathing in microgravity. J ApplPhysiol 67: 15421550, 1989.

60. Permutt S. Pulmonary circulation and the distribution of bloodand gas in the lungs. In: Physiology in the Space Environment.Washington, DC: NAS-NRC, 1967, vol. 1485B, p. 3856.

61. Petrini MF, Peterson BT, and Hyde RW. Lung tissue volumeand blood flow by rebreathing: theory. J Appl Physiol 44: 795802, 1978.

62. Prefaut C, Lupi-h E, and Anthonisen NR. Human lung

mechanics during water immersion. J Appl Physiol 40: 320323,1976.

63. Prisk GK, Elliott AR, Guy HJB, Kosonen JM, and West JB.Pulmonary gas exchange and its determinants during sustainedmicrogravity on Spacelabs SLS-1 and SLS-2. J Appl Physiol 79:12901298, 1995.

64. Prisk GK, Elliott AR, Guy HJB, Verbanck S, Paiva M, andWest JB. Multiple-breath washin of helium and sulfur hexafluo-ride in sustained microgravity. J Appl Physiol 84: 244252,1998.

65. Prisk GK, Elliott AR, and West JB. Sustained microgravityreduces the human ventilatory response to hypoxia but nothypercapnia. J Appl Physiol 88: 14211430, 1999.

66. Prisk GK, Guy HJB, Elliott AR, Deutschman RA III, andWest JB. Pulmonary diffusing capacity, capillary blood volume,and cardiac output during sustained microgravity. J ApplPhysiol 75: 1526, 1993.

67. Prisk GK, Guy HJB, Elliott AR, Paiva M, and West JB. Ventilatory inhomogeneity determined from multiple-breathwashouts during sustained microgravity on Spacelab SLS-1.J Appl Physiol 78: 597607, 1995.

68. Prisk GK, Guy HJB, Elliott AR, and West JB. Inhomogene-ity of pulmonary perfusion during sustained microgravity onSLS-1. J Appl Physiol 76: 17301738, 1994.

69. Prisk GK, Lauzon A-M, Verbanck S, Elliott AR, Guy HJB,Paiva M, and West JB. Anomalous behavior of helium andsulfur hexafluoride during single-breath tests in sustained mi-crogravity. J Appl Physiol 80: 11261132, 1996.

70. Read DJC. A clinical method for assessing the ventilatoryresponse to carbon dioxide. Australas Ann Med 16: 2032, 1967.

71. Rebuck AS and Campbell EJM. A clinical method for assess-ing the ventilatory response to hypoxia. Am Rev Respir Dis 109:345350, 1974.

72. Reed JW, Guy HJB, Hammond MD, and Prisk GK. Mea-surement of ventilation-perfusion inequality: comparison of in-ert gas elimination and intrabreath respiratory exchange ratio(Abstract). Physiologist 29: 931, 1986.

73. Robertson, CH Jr, Engle CM, and Bradley ME. Lung vol-umes in man immersed to the neck: dilution and plethysmo-graphic techniques. J Appl Physiol 44: 679681, 1978.

74. Robertson WG and McRae GL. Study of man during a 56-dayexposure to an oxygen-helium atmosphere at 258 mmHg totalpressure. VII. Respiratory function. Aerospace Med 37: 453456,1966.

75. Sawin CF, Nicogossian AE, Rummel JA, and Michel EL.Pulmonary function evaluation during the Skylab and Apollo-Soyuz Missions. Aviat Space Environ Med 47: 168172, 1976.

76. Serebrovskaya T, Karaban I, Mankovskaya I, Bernardi L,Passino C, and Appenzeller O. Hypoxic ventilatory responsesand gas exchange in patients with Parkinsons disease. Respira-

tion 65: 2833, 1998.77. Shykoff BE, Farhi LE, Olszowka AJ, Pendergast DR, Ro-kitka MA, Eisenhardt CG, and Morin RA. Cardiovascularresponse to submaximal exercise in sustained microgravity.J Appl Physiol Physiol. 81: 2632, 1996.

78. Somers VK, Mark AL, and Abboud FM. Interaction of barore-ceptor and chemoreceptor reflex control of sympathetic nerveactivity in normal humans. J Clin Invest 87: 19531957, 1991.

79. Stone HL, Warren BH, and Wagner H. The distribution opulmonary blood flow in human subjects during zero-G. AGARDConf Proc 2: 129148, 1965.

80. Tenney SM. Fluid volume redistribution and thoracic volumechanges during recumbency. J Appl Physiol 14: 129132, 1959

81. Van Muylem A, DeVuyst P, Yernault J-C, and Paiva M. Inergas single-breath washout and structural alteration of respiratorybronchioles. Am Rev Respir Dis 146: 11671172, 1992.

82. Verbanck S, Larsson H, Linnarsson D, Prisk GK, West JBand Paiva M. Pulmonary tissue volume, cardiac output, and

diffusing capacity in sustained microgravity. J Appl Physiol 83810816, 1997.

83. Verbanck S, Linnarsson D, Prisk GK, and Paiva M. Specifi ventilation distribution in microgravity. J Appl Physiol 8014581465, 1996.

84. Verbanck S, Prisk GK, Guy HJB, West JB, Engel LA, andPaiva M. Ventilation distribution and chest wall mechanics inmicrogravity. In: Proceedings of the Norderney Symposium onScientific Results of the German Spacelab Mission D-2, edited bySahm PR, Keller MH, and Schiewe B. Koln, Germany: Wissenschaftliche Projektfuhrung D-2, 1995, p. 754759.

85. Verbanck S, Schuermans D, Van Muylem A, Paiva MNoppen M, and Vincken W. Ventilation distribution duringhistamine provocation. J Appl Physiol 83: 19071916, 1997.

86. Verbanck S, Weibel ER, and Paiva M. Simulations of washout experiments in postmortem rat lung. J Appl Physiol 75441451, 1993.

87. Videbaek R and Norsk P. Atrial distension in humans duringmicrogravity induced by parabolic flights. J Appl Physiol 8318621866, 1997.

88. Wagner PD, McRae J, and Read J. Stratified distribution oblood flow in secondary lobule of the rat lung. J Appl Physiol 2211151123, 1967.

89. Wagner PD, Saltzman HA, and West JB. Measurement ocontinuous distributions of ventilation-perfusion ratios: theoryJ Appl Physiol 36: 588599, 1974.

90. Waligora JM, Horrigan DJ Jr, and Conkin J. The effect oextended O2 prebreathing on altitude decompression sicknesand venous gas bubbles. Aviat Space Environ Med 58: A110A112. 1987.

91. Wantier M, Estenne M, Verbanck S, Prisk GK, and PaivaM. Chest wall mechanics in sustained microgravity. J AppPhysiol 84: 20602065, 1998.

92. Warrell DA, Evans JW, Clarke RO, Kinagby GP, and WestJB. Patterns of filling in the pulmonary capillary bed. J AppPhysiol 32: 346356, 1972.

93. West JB (Ed.). Blood flow. In: Regional Differences in the LungNew York: Academic, 1977.

94. West JB and Dollery CT. Distribution of blood flow and ventilation-perfusion ratio in the lung, measured with radioactiveCO2. J Appl Physiol 15: 405410, 1960.

95. West JB, Dollery CT, and Naimark A. Distribution of bloodflow in isolated lung: relation to vascular and alveolar pressuresJ Appl Physiol 19: 713724, 1964.

96. West JB, Fowler KT, Hugh-Jones P, and ODonnell TVMeasurement of the ventilation-perfusion ratio inequality in thelung by the analysis of a single expirate. Clin Sci (Colch) 16529547, 1957.

97. West JB and Prisk GK. Chest volume and shape and intrapleural pressure in microgravity. J Appl Physiol 87: 1240

1241, 1999.98. White RJ and Blomqvist CG. Central venous pressure andcardiac function during spaceflight. J Appl Physiol 85: 7387461998.

99. Xie A, Takasaki Y, Popkin J, Orr D, and Bradley TDInfluence of body position on pressure and airflow generationduring hypoxia and hypercapnia in man. J Physiol (Lond) 465477488, 1993.

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