Gravity effects on upper airway area and lung volumes during parabolic flight

We measuredupper airway caliber and lung volumes in six normal subjects in thesitting and supine positions during 20-s periods in normogravity,hypergravity [1.8 + head-to-foot acceleration (G_z)], and microgravity (~0G_z) induced by parabolicflights. Airway caliber and lung volumes were inferred by the acoustic reflection method and inductance plethysmography, respectively. Insubjects in the sitting position, an increase in gravity from 0 to 1.8 +G_z was associated with increasesin the calibers of the retrobasitongue and palatopharyngeal regions(+20 and +30%, respectively) and with a concomitant 0.5-liter increasein end-expiratory lung volume (functional residual capacity, FRC). Insubjects in the supine position, no changes in the areas of theseregions were observed, despite significant decreases in FRC frommicrogravity to normogravity (0.6 liter) and from microgravityto hypergravity (0.5 liter). Laryngeal narrowing also occurredin both positions (about 15%) when gravity increased from 0 to1.8 +G_z. We concluded thatvariation in lung volume is insufficient to explain all upper airwaycaliber variation but that direct gravity effects on tissues surrounding the upper airway should be taken into account.

     

Changes in Doppler mitral inflow patterns during parabolic flight

Aim of the study was to evaluate by transthoracic Doppler the alterations in mitral inflow velocity pattern caused by acute changes in loading conditions occurring during parabolic flights. Each parabola included normogravity (1 Gz, 1 min), mild hypergravity (1.8 Gz, 20 sec), microgravity (0 Gz, 24 sec) and mild hypergravity (1.8 Gz, 20 sec) phases. Pulsed-Doppler images were digitally acquired in 11 unmedicated subjects (46 +/- 5 years), in standing upright position and supine resting. Doppler profiles were semi-automatically traced and inflow parameters extracted and averaged onto three consecutive beats. Only in standing position, significant alterations during microgravity (p<0.05) were noted in several parameters.     

Lung volumes, chest wall configuration, and pattern of breathing in microgravity

We studied the changes in functional residual capacity (FRC), thoracoabdominal volume (Vw), and chest wall configuration in five normal subjects seated in an aircraft flying parabolic trajectories resulting in 20-s periods of microgravity. We measured vital capacity (VC), inspiratory capacity, and tidal volume by integrating airflow at the mouth and changes in rib cage and abdominal volume (delta Vrc and delta Vab, respectively, where delta Vrc + delta Vab = delta Vw) using induction plethysmography. During microgravity (0 Gz) FRC decreased by 413 +/- 70 (SE) ml and VC by 0.37 liter. The decrease in Vw did not differ from that in FRC and was entirely the result of reduction of Vab, the Vrc showing no significant change. During tidal breathing the abdominal contribution (delta Vab/delta Vw) increased from 0.39 +/- 0.08 at 1 Gz to 0.57 +/- 0.08 at 0 Gz. During brief periods of hypergravity (approximately 1.8 Gz) all changes were opposite in sign and relatively smaller. Limited data during "roller coaster" flight patterns suggested that, in contrast to configurational changes, the temporal pattern of breathing was uninfluenced by changes in Gz. We conclude that at the onset of weightlessness there are substantial changes in lung volume and thoracoabdominal configuration. Abdominal contribution to tidal excursions increases but the temporal pattern of breathing is unchanged.     

Inter- and intraregional ventilation inhomogeneity in hypergravity and after pressurization of an anti-G suit.

This study assessed the effects of increased gravity in the head-to-foot direction (+G(z)) and anti-G suit (AGS) pressurization on functional residual capacity (FRC), the volume of trapped gas (V(TG)), and ventilation distribution by using inert- gas washout. Normalized phase III slope (Sn(III)) analysis was used to determine the effects on inter- and intraregional ventilation inhomogeneity. Twelve men performed multiple-breath washouts of SF(6) and He in a human centrifuge at +1 to +3 G(z) wearing an AGS pressurized to 0, 6, or 12 kPa. Hypergravity produced moderately increased FRC, V(TG), and overall and inter- and intraregional inhomogeneities. In normogravity, AGS pressurization resulted in reduced FRC and increased V(TG), overall, and inter- and intraregional inhomogeneities. Inflation of the AGS to 12 kPa at +3 G(z) reduced FRC markedly and caused marked gas trapping and intraregional inhomogeneity, whereas interregional inhomogeneity decreased. In conclusion, increased +G(z) impairs ventilation distribution not only between widely separated lung regions, but also within small lung units. Pressurizing an AGS in hypergravity causes extensive gas trapping accompanied by reduced interregional inhomogeneity and, apparently, results in greater intraregional inhomogeneity.     

Effects of gravity on lung diffusing capacity and cardiac output in prone and supine humans.

Both in normal subjects exposed to hypergravity and in patients with acute respiratory distress syndrome, there are increased hydrostatic pressure gradients down the lung. Also, both conditions show an impaired arterial oxygenation, which is less severe in the prone than in the supine posture. The aim of this study was to use hypergravity to further investigate the mechanisms behind the differences in arterial oxygenation between the prone and the supine posture. Ten healthy subjects were studied in a human centrifuge while exposed to 1 and 5 times normal gravity (1 G, 5 G) in the anterioposterior (supine) and posterioanterior (prone) direction. They performed one rebreathing maneuver after approximately 5 min at each G level and posture. Lung diffusing capacity decreased in hypergravity compared with 1 G (ANOVA, P = 0.002); it decreased by 46% in the supine posture compared with 25% in the prone (P = 0.01 for supine vs. prone). At the same time, functional residual capacity decreased by 33 and 23%, respectively (P < 0.001 for supine vs. prone), and cardiac output by 40 and 31% (P = 0.007 for supine vs. prone), despite an increase in heart rate of 16 and 28% (P < 0.001 for supine vs. prone), respectively. The finding of a more impaired diffusing capacity in the supine posture compared with the prone at 5 G supports our previous observations of more severe arterial hypoxemia in the supine posture during hypergravity. A reduced pulmonary-capillary blood flow and a reduced estimated alveolar volume can explain most of the reduction in diffusing capacity when supine.     

Exercise-induced bronchodilation in natural and induced asthma: effects on ventilatory response and performance.

We studied whether bronchodilatation occurs with exercise during the late asthmatic reaction (LAR) to allergen (group 1, n = 13) or natural asthma (NA; group 2, n = 8) and whether this is sufficient to preserve maximum ventilation (VE(max)), oxygen consumption (VO(2 max)), and exercise performance (W(max)). In group 1, partial forced expiratory flow at 30% of resting forced vital capacity increased during exercise, both at control and LAR. W(max) was slightly reduced at LAR, whereas VE(max), tidal volume, breathing frequency, and VO(2 max) were preserved. Functional residual capacity and end-inspiratory lung volume were significantly larger at LAR than at control. In group 2, partial forced expiratory flow at 30% of resting forced vital capacity increased greatly with exercise during NA but did not attain control values after appropriate therapy. Compared with control, W(max) was slightly less during NA, whereas VO(2 max) and VE(max) were similar. Functional residual capacity, but not end-inspiratory lung volume at maximum load, was significantly greater than at control, whereas tidal volume decreased and breathing frequency increased. In conclusion, remarkable exercise bronchodilation occurs during either LAR or NA and allows VE(max) and VO(2 max) to be preserved with small changes in breathing pattern and a slight reduction in W(max).     

Distributions of lung ventilation and perfusion in prone and supine humans exposed to hypergravity.

When normal subjects are exposed to hypergravity [5 times normal gravity (5 G)] there is an impaired arterial oxygenation that is less severe in the prone compared with supine posture. We hypothesized that under these conditions the heterogeneities of ventilation and/or perfusion distributions would be less prominent when subjects were prone compared with supine. Expirograms from a combined rebreathing-single breath washout maneuver (Rohdin M, Sundblad P, and Linnarsson D. J Appl Physiol 96: 1470-1477, 2004) were analyzed for vital capacity (VC), phase III slope, and phase IV amplitude, to analyze heterogeneities in ventilation (Ar) and perfusion [CO(2)-to-Ar ratio (CO(2)/Ar)] distribution, respectively. During hypergravity, VC decreased more in the supine than in the prone position (ANOVA, P = 0.02). Phase III slope was more positive for Ar (P = 0.003) and more negative for CO(2)/Ar (P = 0.007) in the supine compared with prone posture at 5 G, in agreement with the notion of a more severe hypergravity-induced ventilation-perfusion mismatch in supine posture. Phase IV amplitude became lower in the supine than in the prone posture for both Ar (P = 0.02) and CO(2)/Ar (P = 0.004) during hypergravity as a result of the more reduced VC in the supine posture. We speculate that results of VC and phase IV amplitude are due to the differences in heart-lung interaction and diaphragm position between postures: a stable position of the heart and diaphragm in prone hypergravity, in contrast to supine in which the weight of the heart and a cephalad shift of the diaphragm compress lung tissue.     

Regional ventilation during spontaneous breathing and mechanical ventilation in dogs

We evaluated the effects of the different patterns of chest wall deformation that occur with different body positions and modes of breathing on regional lung deformation and ventilation. Using the parenchymal marker technique, we determined regional lung behavior during mechanical ventilation and spontaneous breathing in five anesthetized recumbent dogs. Regional lung behavior was related to the patterns of diaphragm motion estimated from X-ray projection images obtained at functional residual capacity (FRC) and end inspiration. Our results indicate that 1) in the prone and supine positions, FRC was larger during mechanical ventilation than during spontaneous breathing; 2) there were significant differences in the patterns of diaphragm motion and regional ventilation between mechanical ventilation and spontaneous breathing in both body positions; 3) in the supine position only, there was a vertical gradient in lung volume at FRC; 4) in both positions and for both modes of breathing, regional ventilation was nonlinearly related to changes in lobar and overall lung volumes; and 5) different patterns of diaphragm motion caused different sliding motions and differential rotations of upper and lower lobes. Our results are inconsistent with the classic model of regional ventilation, and we conclude that the distribution of ventilation is determined by a complex interaction of lung and chest wall shapes and by the motion of the lobes relative to each other, all of which help to minimize distortion of the lung parenchyma.     

Effect of gravity and posture on lung mechanics.

The volume-pressure relationship of the lung was studied in six subjects on changing the gravity vector during parabolic flights and body posture. Lung recoil pressure decreased by approximately 2.7 cmH(2)O going from 1 to 0 vertical acceleration (G(z)), whereas it increased by approximately 3.5 cmH(2)O in 30 degrees tilted head-up and supine postures. No substantial change was found going from 1 to 1.8 G(z). Matching the changes in volume-pressure relationships of the lung and chest wall (previous data), results in a decrease in functional respiratory capacity of approximately 580 ml at 0 G(z) relative to 1 G(z) and of approximately 1,200 ml going to supine posture. Microgravity causes a decrease in lung and chest wall recoil pressures as it removes most of the distortion of lung parenchyma and thorax induced by changing gravity field and/or posture. Hypergravity does not greatly affect respiratory mechanics, suggesting that mechanical distortion is close to maximum already at 1 G(z). The end-expiratory volume during quiet breathing corresponds to the mechanical functional residual capacity in each condition.     

Effects of rapid saline infusion on lung mechanics and airway responsiveness in humans.

Lung mechanics and airway responsiveness to methacholine (MCh) were studied in seven volunteers before and after a 20-min intravenous infusion of saline. Data were compared with those of a time point-matched control study. The following parameters were measured: 1-s forced expiratory volume, forced vital capacity, flows at 40% of control forced vital capacity on maximal (Vm(40)) and partial (Vp(40)) forced expiratory maneuvers, lung volumes, lung elastic recoil, lung resistance (Rl), dynamic elastance (Edyn), and within-breath resistance of respiratory system (Rrs). Rl and Edyn were measured during tidal breathing before and for 2 min after a deep inhalation and also at different lung volumes above and below functional residual capacity. Rrs was measured at functional residual capacity and at total lung capacity. Before MCh, saline infusion caused significant decrements of forced expiratory volume in 1 s, Vm(40), and Vp(40), but insignificantly affected lung volumes, elastic recoil, Rl, Edyn, and Rrs at any lung volume. Furthermore, saline infusion was associated with an increased response to MCh, which was not associated with significant changes in the ratio of Vm(40) to Vp(40). In conclusion, mild airflow obstruction and enhanced airway responsiveness were observed after saline, but this was not apparently due to altered elastic properties of the lung or inability of the airways to dilate with deep inhalation. It is speculated that it was likely the result of airway wall edema encroaching on the bronchial lumen.     

Dispersion of 0.5- to 2-micron aerosol in microG and hypergravity as a probe of convective inhomogeneity in the lung.

We used aerosol boluses to study convective gas mixing in the lung of four healthy subjects on the ground (1 G) and during short periods of microgravity (microG) and hypergravity ( approximately 1. 6 G). Boluses of 0.5-, 1-, and 2-micron-diameter particles were inhaled at different points in an inspiration from residual volume to 1 liter above functional residual capacity. The volume of air inhaled after the bolus [the penetration volume (Vp)] ranged from 150 to 1,500 ml. Aerosol concentration and flow rate were continuously measured at the mouth. The dispersion, deposition, and position of the bolus in the expired gas were calculated from these data. For each particle size, both bolus dispersion and deposition increased with Vp and were gravity dependent, with the largest dispersion and deposition occurring for the largest G level. Whereas intrinsic particle motions (diffusion, sedimentation, inertia) did not influence dispersion at shallow depths, we found that sedimentation significantly affected dispersion in the distal part of the lung (Vp >500 ml). For 0.5-micron-diameter particles for which sedimentation velocity is low, the differences between dispersion in microG and 1 G likely reflect the differences in gravitational convective inhomogeneity of ventilation between microG and 1 G.     

Antibody binding in altered gravity: implications for immunosorbent assay during space flight

A single antibody-incubation step of an indirect, enzyme-linked immunosorbent assay (ELISA) was performed during microgravity, Martian gravity (0.38 G) and hypergravity (1.8 G) phases of parabolic flight, onboard the NASA KC-135 aircraft. Antibody-antigen binding occurred within 15 seconds; the level of binding did not differ between microgravity, Martian gravity and 1 G (Earth's gravity) conditions. During hypergravity and 1 G, antibody binding was directly proportional to the fluid volume (per microtiter well) used for incubation; this pattern was not observed during microgravity. These effects in microgravity may be due to "fluid spread" within the chamber (observed during microgravity with digital photography), leading to greater fluid-surface contact and subsequently antibody-antigen contact. In summary, these results demonstrate that: i) ELISA antibody-incubation and washing steps can be successfully performed by human operators during microgravity, Martian gravity and hypergravity; ii) there is no significant difference in antibody binding between microgravity, Martian gravity and 1 G conditions; and iii) a smaller fluid volume/well (and therefore less antibody) was required for a given level of binding during microgravity. These conclusions indicate that reduced gravity would not present a barrier to successful operation of immunosorbent assays during spaceflight.     

Biomechanics and regulation of external respiration under conditions of five-day dry immersion

The functional state of external respiration and the features of its regulation in healthy persons were studied under conditions of microgravity simulated using dry immersion. The lung volume, the ratio of thoracic and abdominal components during quiet breathing and performing various respiratory maneuvers, as well as the parameters that characterize the regulation of breathing (the duration of breath holding and the ability to voluntarily control respiratory movements), were recorded during the baseline period, on days 2 and 4 of dry immersion, and after the end of the dry immersion. It has been shown that the breathing pattern did not significantly change under conditions of dry immersion compared to the baseline period; however, the inspiratory reserve volume increased (p < 0.05), while the expiratory reserve volume decreased (p < 0.01). Dry immersion did not alter pulmonary ventilation, yet most of the subjects trended toward an increase in the contribution of the abdominal component of breathing movements during quiet breathing and demonstrated a statistically significant increase in this parameter during the lung vital capacity maneuver. The durations of the inspiratory and expiratory maximal breath holding under conditions of immersion did not differ from the background values. During the immersion, the accuracy of voluntary control of breathing increased. We believe that immersion, similar to microgravity, leads to changes in the reserve lung volume, which are partly because of changes in the body position; changes in relative contributions of the thoracic and abdominal components in the breathing movements; and changes in voluntary breath regulation.     

Increased gravitational stress does not alter maximum expiratory flow

We measured maximum expiratory flow-volume (MEFV) curves in six seated subjects during normal (+1 Gz) and increased (+2 and +3 Gz) gravitational stress. Full MEFV curves, initiated at total lung capacity, were recorded, as were partial MEFV curves, initiated at approximately 60% of the vital capacity. Data were acquired in all subjects breathing air at +1 and +2 Gz; results were available for three subjects breathing 80% He-20% O2 at +1 and +2 Gz, and in two subjects, results were obtained at +3 Gz. Changes in gravitational stress were not associated with changes of either full or partial MEFV curves. The known increase in differences of regional lung volume and recoil caused by increased gravitational stress did not influence maximum expiratory flow. Though increased gravitational stress probably changed regional emptying sequences little during full MEFV maneuvers, substantial changes of emptying sequence were expected during partial maneuvers. It is possible that such changes in emptying sequence occurred but were not associated with changes in maximum flow because the latter was determined by choking in central airways common to all regions.     

Tidal volume single-breath washin of SF6 and CH4 in transient microgravity.

We performed tidal volume single-breath washins (SBW) by using tracers of different diffusivity and varied the time spent in microgravity (microG) before the start of the tests to look for time-dependent effects. SF(6) and CH(4) phase III slopes decreased by 35 and 26%, respectively, in microG compared with 1 G (P < 0.05), and the slope difference between gases disappeared. There was no effect of time in microG, suggesting that neither the hypergravity period preceding microG nor the time spent in microG affected gas mixing at volumes near functional residual capacity. In previous studies using SF(6) and He (Lauzon A-M, Prisk GK, Elliott AR, Verbanck S, Paiva M, and West JB. J Appl Physiol 82: 859-865, 1997), the vital capacity SBW showed an increase in slope difference between gases in transient microG, the opposite of the decrease in sustained microG. In contrast, tidal volume SBW showed a decrease in slope difference in both microG conditions. Because it is only the behavior of the more diffusive gas that differed between maneuvers and microG conditions, we speculate that, in the previous vital capacity SBW, the hypergravity period preceding the test in transient microG provoked conformational changes at low lung volumes near the acinar entrance.     

Single-breath washouts in a rotating stretcher.

Vital capacity single-breath washouts using 90% O2-5% He-5% SF6 as a test gas mixture were performed with subjects sitting on a stool (upright) or recumbent on a stretcher (prone, supine, lateral left, lateral right, with or without rotation at end of inhalation). On the basis of the combinations of supine and prone maneuvers, gravity-dependent contributions to N2 phase III slope and N2 phase IV height in the supine posture were estimated at 18% and 68%, respectively. Whereas both He and SF6 slope decreased from supine to prone, the SF6-He slope difference actually increased (P = 0.015). N2 phase III slopes, phase IV heights, and cardiogenic oscillations were smallest in the prone posture, and we observed similarities between the modifications of He and SF6 slopes from upright to prone and from upright to short-term microgravity. These results suggest that phase III slope is partially due to emptying patterns of small units with different ventilation-to-volume ratios, corresponding to acini or groups of acini. Of all body postures under study, the prone position most reduces the inhomogeneities of ventilation during a vital capacity maneuver at both inter- and intraregional levels.     

Breathing during exercise in subjects with mild-to-moderate airflow obstruction: effects of physical training.

In this study we explored the effects of physical training on the response of the respiratory system to exercise. Eight subjects with irreversible mild-to-moderate airflow obstruction [forced expiratory volume in 1 s of 85 +/- 14 (SD) % of predicted and ratio of forced expiratory volume in 1 s to forced vital capacity of 68 +/- 5%] and six normal subjects with similar anthropometric characteristics underwent a 2-mo physical training period on a cycle ergometer three times a week for 31 min at an intensity of approximately 80% of maximum heart rate. At this work intensity, tidal expiratory flow exceeded maximal flow at control functional residual capacity [FRC; expiratory flow limitation (EFL)] in the obstructed but not in the normal subjects. An incremental maximum exercise test was performed on a cycle ergometer before and after training. Training improved exercise capacity in all subjects, as documented by a significant increase in maximum work rate in both groups (P < 0.001). In the obstructed subjects at the same level of ventilation at high workloads, FRC was greater after than before training, and this was associated with an increase in breathing frequency and a tendency to decrease tidal volume. In contrast, in the normal subjects at the same level of ventilation at high workloads, FRC was lower after than before training, so that tidal volume increased and breathing frequency decreased. These findings suggest that adaptation to breathing under EFL conditions does not occur during exercise in humans, in that obstructed subjects tend to increase FRC during exercise after experiencing EFL during a 2-mo strenuous physical training period.     

Effect of microgravity on the respiratory system.

Because the pleural pressure gradient and regional distribution of pulmonary function are gravity dependent, substantial changes may be expected during weightlessness. Although very few measurements have been made during spaceflights, a number of observations during brief periods of weightlessness inside aircraft flying with parabolic trajectories confirm these predictions. Single-breath N2 washouts suggest a marked reduction in the inequality of ventilation distribution seen at 1 G. Similarly, inferences made from cardiogenic oscillations during single-breath washouts suggest a greater uniformity of perfusion during weightlessness. This is supported by changes seen on chest radiographs as well as by more direct measurements of regional blood flow distribution using radioactive iodine-labeled macroaggregates. Vital capacity is only slightly reduced, but functional residual capacity decreases by approximately 10% and maximum expiratory flow rates are slightly decreased, especially at low lung volumes. Weightlessness decreases abdominal girth, increases abdominal compliance, and substantially increases the abdominal contribution to tidal volume during resting breathing. Despite these changes, there does not appear to be any alteration in the temporal pattern of breathing. However, the deposition of inhaled medium-sized aerosol particles is substantially reduced, as predicted by model analyses of gravitational sedimentation. Virtually all these observations describe effects at the very onset of weightlessness. Practically nothing is known of slower functional changes and adaptations to prolonged weightlessness. Systematic repeated measurements during manned spaceflights will hopefully begin to provide some information on this subject in the near future.     

The development of vestibular connections in rat embryos in microgravity

Existing experimental embryological data suggests that the vestibular system initially develops in a very rigid and genetically controlled manner. Nevertheless, gravity appears to be a critical factor in the normal development of the vestibular system that monitors position with respect to gravity (saccule and utricle). In fact several studies have shown that prenatal exposure to microgravity causes temporary deficits in gravity-dependent righting behaviors, and prolonged exposure to hypergravity from conception to weaning causes permanent deficits in gravity-dependent righting behaviors. Data on hypergravity and microgravity exposure suggest some changes in the otolith formation during development, in particular the size although these changes may actually vary with the species involved. In adults exposed to microgravity there is a change in the synaptic density in the optic sensory epithelia suggesting that some adaptation may occur there. However, effects have also been reported in the brainstem. Several studies have shown synaptic changes in the lateral vestibular nucleus and in the nodulus of the cerebellum after neonatal exposure to hypergravity. We report here that synaptogenesis in the medial vestibular nucleus is retarded in developing rat embryos that were exposed to microgravity from gestation days 9 to 19.     

Microgravity and the lung.

Although environmental physiologists are readily able to alter many aspects of the environment, it is not possible to remove the effects of gravity on Earth. During the past decade, a series of space flights were conducted in which comprehensive studies of the lung in microgravity (weightlessness) were performed. Stroke volume increases on initial exposure to microgravity and then decreases as circulating blood volume is reduced. Diffusing capacity increases markedly, due to increases in both pulmonary capillary blood volume and membrane diffusing capacity, likely due to more uniform pulmonary perfusion. Both ventilation and perfusion become more uniform throughout the lung, although much residual inhomogeneity remains. Despite the improvement in the distribution of both ventilation and perfusion, the range of the ventilation-to-perfusion ratio seen during a normal breath remains unaltered, possibly because of a spatial mismatch between ventilation and perfusion on a small scale. There are unexpected changes in the mixing of gas in the periphery of the lung, and evidence suggests that the intrinsic inhomogeneity of the lung exists at a scale of an acinus or a few acini. In addition, aerosol deposition in the alveolar region is unexpectedly high compared with existing models.