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1TBM Lab, Dipartimento di Bioingegneria, Politecnico di Milano, I-20133 Milan; and 2Dipartimento di Medicina Sperimentale, Ambientale e Biotecnologie Mediche, Università di Milano-Bicocca, I-20052 Monza, Italy; and 3Médecine Aerospatiale, Université de Bordeaux, F-33076 Bordeaux, France
Submitted 11 August 2003 ; accepted in final form 13 May 2004
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ABSTRACT |
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23%), reflecting an increase in mean inspiratory flow rate, tidal volume, and respiratory frequency, while ventilation decreased (approximately –14%), shifting to supine posture (transition time 
15 s). These data suggest a remarkable feature in the mechanical arrangement of the respiratory system such that it can maintain the ventilatory output with small changes in inspiratory muscle work in face of considerable changes in configuration and mechanical properties. microgravity; respiratory mechanics; respiratory control; pulmonary ventilation
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METHODS |
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TOPABSTRACTMETHODSRESULTSDISCUSSIONGRANTSACKNOWLEDGMENTSREFERENCES |
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20 s. Subjects. Respiratory variables [lung volume and esophageal pressure (Pes)] were obtained during steady horizontal flight and during short periods of microgravity and hypergravity in four male (age: 53 ± 2 yr; weight: 74 ± 3 kg; height: 174 ± 1 cm) and one female (age: 40 yr; weight: 61 kg; height: 167 cm) subjects. All subjects were healthy nonsmokers with no preexisting pulmonary disease. The same subjects were also studied during ground experiments in a sitting and supine posture with the use of the same equipment. The subjects had previous parabolic flight experience, were trained to perform the respiratory maneuvers, and were well accustomed to abrupt changes in Gz, which could occur several times during each flight. This same subject set had previously performed studies on how changes in Gz affect chest wall and lung mechanics (5, 6). Subjects gave their informed consent, and the protocol was approved by a review board.
Experimental equipment and system.
Subjects were seated in a body plethysmograph made of wood (empty volume of 360 liters), which was equipped with a pneumothachograph and transducers to measure pressure changes in the box and at the mouth (Pm). Panting maneuvers were performed by using a mouthpiece provided with an electromagnetic shutter. We initially performed parabolas with the transducers alone to evaluate the response of the transducer signals to changes in acceleration. The transducers were orientated along the aircraft's transverse axis to minimize the effect of changes in aircraft accelerations on both transducers. Lung volumes were measured by integrating the flow signal. Pes was derived from a pressure transducer mounted on a Gaeltec CTO-2 catheter (2-mm external diameter). Transducer sensitivity and linear pressure ranges were 5 µV·V–1·mmHg–1 and ±300 mmHg, respectively. The subjects were trained to advance the catheter through their nose until the location of the esophageal recording site was the one determined during preliminary on-ground experiments (on, average, 15 cm below the jugular notch, which roughly corresponds to the apex of the lung). The location of the esophageal transducer was chosen to minimize cardiac artifact and stabilize the pressure signal.
The pneumotachograph response was linear for flow rates compatible with the respiratory maneuvers performed with a maximum error of 5% at high-flow rates (3 l/s). All signals were sampled with an analog-to-digital converter (Digimétrie; 50 Hz/channel). Online analysis was performed to quantify the lung volumes from the pneumotachograph flow and plethysmograph pressure signals. The current lung volume, pressure variables, and Gz were monitored on a video screen during the experiment.
Calibration. Before take off, calibration of the plethysmograph was performed by using a 2-liter syringe. A syringe volume control was custom made for each subject to be used during the flight. Calibration for the body box and Pm transducers was carried out by using a water manometer. Cabin pressure tended to decrease during the ascending phase and to increase during the descending phase; hence, the plethysmograph would overestimate lung volume during the ascending phase and underestimate lung volume during the descending phase. Cabin pressure was manually checked and corrected during the parabola for mismatches in pressure. From the 30 parabolas that were checked, the overall change in lung volume during the 0-Gz phase due to mismatch in pressure correction averaged 0.029 ± 0.27 liters, or 0.6% of vital capacity (VC) (a nonsignificant underestimate).
The Pes transducers were calibrated by using a calibration chamber, which could set the pressure by using water manometers. The sensitivity of the transducers and zero drift at atmospheric pressure were recorded. The sensitivity of the transducer was independent of temperature, whereas the zero drift was slightly dependent on temperature. The zero value corresponding to body temperature was obtained by withdrawing the probe at the end of each experimental session. These zero values were then used to correct Pes previously recorded.
Protocols for in-flight experiments. Subjects were seated inside the plethysmograph while breathing through the mouthpiece. During 0-Gz exposure, the subjects would float up due to the changing trajectory of the aircraft. To counteract the effect, the subjects were secured to their seat with straps at their thighs and feet. Loose bands around the arms kept the arms positioned parallel to the chest. The time frame for data acquisition during respiratory maneuvers started in the last minute of level flight (1 Gz): pull up (1.8 Gz, 20 s), injection (0 Gz, 20 s), pull out (1.8 Gz, 20 s), and level flight again (1 Gz). The subjects were asked to breathe quietly throughout the various phases of the parabolic flight. The subjects were also asked to perform a VC and panting maneuvers to measure total gas volume (TGV) at the onset of the 1-Gz phase, before the parabola, and after returning to 1 Gz after the parabola. The total number of parabolas necessary to gather a complete set of data for each subject varied from 15 to 20 times.
Protocol for ground experiments.
Ground experiments were performed, in the seated and supine position, on the same subjects, adopting the same protocol and equipments as during the in-flight experiments. The change in posture was obtained by leaning the plethysmograph backward; this implied that legs remained as in the sitting posture. This change of position was completed in 15 s. This time is slightly longer than that corresponding to the in-flight changing Gz, which was on the order of 5 s.
Data analysis.
TGVs were computed from Boyle's law:
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V/Pm is the ratio of change () in thoracic volume (V) to the change in alveolar pressure (Pm) during panting maneuvers. The ratio was inferred from the slope of the linear regression between volume and Pm. The drift of the volume measurement was initially subtracted from the volume signal of the panting maneuvers so that regression coefficients were 0.99, suggesting an accurate TGV measurement. Lung volume recorded throughout the time frame also displayed a drift because of increasing temperature inside the plethysmograph. The lung volumes were obtained after correcting for volume drift between two successive TGV values, assuming a linear drift with time. Pes data were corrected for the zero drift on withdrawal of the catheter at the end of the session. A "moving average filter" that uses a moving window of 30 samples was employed to reduce high-frequency noise in the pressure records.
Lung resistance (RL) (airway plus lung tissue resistance) was calculated according to Mead and Whittenberger (18).
The number of respiratory cycles for each in-flight phase was four to five. The total number of respiratory cycles considered for 0 Gz ranged from 60 to 100.
Each respiratory cycle analyzed was normalized to 100 time interval units. Readings of tidal volume (VT) and Pes were done at each interval unit.
Statistical analysis. Values, if not otherwise specified, are presented as means ± SE. A nonparametric Wilcoxon’s test determined statistical significance of changes between different conditions. Significance was taken as P < 0.05.
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RESULTS |
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33%) only when passing from 1 to 1.8 Gz. Significant changes in resistive WI were found only when passing from 1 to 0 Gz. Inspiratory resistive work accounted for a share of the total WI, ranging from a minimum of 17% at 1 Gz to a maximum of 32% at 0 Gz. Table 1 also shows that there were no significant changes observed in resistive expiratory work.
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1,200 ml (5)]. Furthermore, in the supine posture, the elastic energy released by the chest wall was significantly reduced, as shown by the rightward shift of the volume-pressure curve. Thus, as a first approximation, the condition at 0 Gz is comparable to supine, although the mechanisms are in part similar (rightward displacement of chest wall PV curve) and in part different (much larger decrease in FRC in supine). On average, in the supine posture, the net elastic WI remained essentially equal to that at 1 Gz. Finally, at 1.8 Gz, no consistent changes in elastic properties of lung and chest wall were observed nor in FRC, and, accordingly, the elastic components of WI were essentially unchanged relative to 1 Gz. Thus, again to a first approximation, 1 Gz is equivalent to 1.8 Gz.
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RL values are reported in Table 1 and show that RL increases significantly in the supine posture relative to all other conditions.
Pattern of breathing.
Table 2 summarizes data on the timing and pattern of breathing and the corresponding changes in pulmonary ventilation as given by
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E is ventilation, TI is inspiratory time, TT is total time, and TI/TT is commonly referred to as the duty cycle. E varied in the conditions studied as a combination of changing both VT/TI and duty cycle (Fig. 4A). Considering E = f·VT, where f is the respiratory frequency, one can appreciate that changes in ventilation are accomplished by parallel changes in VT and f (Fig. 4B). Therefore, data from Fig. 4 indicate that resting pulmonary ventilation is affected by changing gravity and posture.
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WI can be expressed as function of RL, CT, and volume V, considering the classic equation of motion for breathing (assuming that the effect of inertial forces during quiet breathing was negligible):
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is the flow of the airway opening. CT and RL are assumed to be constant during quiet breathing. From the differential expression for work dW = P dV, substituting the expression for P from Eq. 1, supposing that the lung volume during quiet breathing can be approximated by a sine wave (8), and integrating over an inspiration, the WI can be expressed as:
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 | (3) |
Figure 5 shows the results of the analysis. When switching from 1 to 1.8 Gz, the energy output of the inspiratory muscles available at 1 Gz would cause VT to decrease mostly due to the decrease in CT, yet the actual VT at 1.8 Gz was slightly larger than at 1 Gz, suggesting an increase in energy output. When switching from 1.8 to 0 Gz, the respiratory output available at 1.8 Gz would cause a large increase in VT, but, because the actual increase was much less, this suggests that a decrease in energy output has occurred. When returning from 0 to 1.8 Gz, a marked decrease in VT would be expected, but the actual decrease is much less (no difference was found in pattern of breathing between the rising and descending phase at 1.8 Gz), and, therefore, an increase in energy output should have occurred. Returning from 1.8 to 1 Gz would deliver energy to cause an increase in VT, but, because the actual VT returns toward the control value, a decrease in total output should have occurred. Moving from sitting to supine would be expected to cause a decrease in VT for the same energy expenditure, mostly due to the decrease in RL; however, the observed decrease in VT was larger than expected.
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DISCUSSION |
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Changes in resistive and elastic work. FRC is lower in supine than at 0 Gz, and this can partly explain the increase in RL (Fig. 6), as a hyperbolic relationship has been described between RL and lung volume (7). One may interpret this finding, considering that the deformation of the lung due to gravity should be reduced in weightlessness, and, therefore, all lung regions are more uniformly expanded (17, 19). In this condition, the contribution of the heterogeneity of time constants throughout the lung to total RL should be reduced (20), resulting in a lower RL around breathing frequencies.
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30% of the total WI. Therefore, changes in the resistance due to changes in Gz affect the total respiratory work only marginally. Because the elastic properties of lung and chest wall are affected by changing Gz, the lung and chest wall components to the elastic work are also significantly changed (Fig. 3A).
Changes in ventilatory pattern and control of breathing. The data from Fig. 5 allow discussion of the complex matching between the work of breathing and control of the neuromuscular respiratory output in response to loading and unloading of the respiratory muscles. These data were obtained by applying the model described by Eqs. 2 and 3, based on three important assumptions: 1) the hypothesis of sinusoidal VT; 2) the equation of motion (Eq. 1) accurately describes the dynamics of the respiratory system; and 3) the contribution of chest wall resistance is negligible. To validate our model, we compared the measured VT to the computed VT obtained by solving Eq. 3 using the mechanical properties and the breathing pattern for the same condition. WI and compliance values were measured on the volume-pressure curves, the RL was measured by using the Mead and Whittenberger method, and the f was measured on volume traces. The validity of the model was satisfactory, as the predicted VT values differed by no more than 9% from the measured VT in each condition.
We found that increasing the load results in a larger inspiratory output; however, the resultant VT may either increase (switching from 1 to 1.8 Gz) or decrease (switching from 0 to 1.8 Gz), reflecting a greater decrease in the respiratory compliance in the latter case. Unloading always induces a decrease in inspiratory output: the resulting VT decreased from 2 to 1 Gz but increased moving from 2 to 0 Gz, reflecting a larger increase in respiratory compliance. A decrease in respiratory neural drive was also found on immersion in water up to the xiphoid process, a situation mimicking the exposure to microgravity because it counteracts the weight of the abdomen (23). These immediate responses occurred through combined and coordinated modifications in VT and in inspiratory flow rate, with minor changes in duty cycle and f (Fig. 4).
Because the metabolic demand is unchanged on quickly varying Gz and posture, the question arises as to how the breathing pattern is affected when the operational features of the respiratory muscles are modified. Despite changes in elastic features and configuration, the respiratory system is allowed to return to its resting mechanical point on expiration; therefore, this suggests that the control of breathing pattern mainly acts on inspiratory muscles, namely external intercostals and diaphragm. Although these two groups of muscles work together to operate the respiratory pump, they are affected differently by force-length properties due to changes in configuration, in particular considering the abdominal and the rib cage contribution to total lung volume. Furthermore, they are also subject to a different reflex control from proprioceptors as external intercostals are rich in spindles, whereas the diaphragm is rich in Golgi tendon organs (24).
We did not find significant differences between the tidal breaths within the 20 s of a given Gz exposure. This suggests that the response in the breathing pattern is accomplished within a short time (less than one breath) of changing the mechanical properties of the respiratory system. This prompt respiratory response is compatible with the short time constants of the control mechanisms.
Previous studies considered how the respiratory pattern is affected by changing the respiratory load through a decrease (breathing He-O2 mixture) or an increase in airway resistance (returning to air breathing) (15). The immediate response to loading (returning from He to room air breathing) consisted of an increase in VT and ventilation, which is in line with our findings when moving from 1 to 1.8 Gz. The immediate response to unloading (switching from room air to He breathing) was again an increase in ventilation due to an increase in frequency but a decrease in VT. We found that, when unloading from 1.8 to 1 G2 (with a 23% increase in compliance), both ventilation and VT decreased. Conversely, when unloading from 1.8 to 0 Gz (with an increase in compliance as large as 71%), we found that both ventilation and VT increased.
The use of He-O2 mixture allows changes only in pulmonary resistance to 20% (9). In our case, loading and unloading were mainly due to changes in respiratory compliance, with negligible effects on RL. Therefore, during the He experiments, the change of the load applied to inspiratory muscles is mainly proportional to the inspiratory flow. Conversely, when changing gravity, the load to inspiratory muscles is mainly proportional to the lung volume. Given these differences, it is conceivable to hypothesize that there are also differences in afferent input and reflex control between the two conditions.
The overshoot in VT on unloading was also observed on removal of external resistances in both animals (15, 16) and humans (1). This effect can be explained by extending our hypothesis to say that a given inspiratory output necessary to overcome either elastance (mostly our case) or resistance (1, 15, 16) may result in some overshoot of ventilation when loading is suddenly removed, despite some immediate control.
The bulk of these data seem to rule out the importance of pulmonary vagal afferents to detect respiratory loads and to contribute to a load compensation response (16, 24, 26).
A volitional component in the respiratory response could be invoked, as our subjects were aware of the incoming condition due to a repetitive experimental protocol. However, we may comment that they were starting inspiration always at FRC under the various conditions, despite considerable changes in configuration of the respiratory system, suggesting that they were breathing "quietly"; accordingly, these considerations would rule out a volitional component.
Comparison to previous in-flight data and to supine and water immersion. A previous study on parabolic flights showed no difference in VT between 1 and 1.8 Gz (21) and a small, although insignificant, increase in VT at 0 Gz compared with control (11). Interestingly, during sustained microgravity, VT was found to be significantly decreased relative to preflight standing control but also, although not significantly, relative to supine (12). On comparing 0-Gz acute exposure to supine, the former leads to hyperventilation relative to control, whereas the latter leads to hypoventilation (Fig. 4 and Table 2), yet the two conditions share various similarities. Switching from 1 to 0 Gz or from standing to supine position causes 1) a cranial displacement of the diaphragm, modifying both lung volumes and chest wall configuration (21, 25), 2) a decrease of inspiratory muscle activity (10, 13), 3) a blood shift from lower body to thorax (14, 22), and 4) a decrease in FRC.
The decrease in ventilation when shifting from sitting to supine confirms what has been previously found (2, 4) and could be replicated by water immersion up to the xyphoid (2). One may postulate that the increase in VT observed at 0 Gz during parabolic flights might relate to the specific conditions occurring during the flight. To explore this possibility, one could estimate what the effect of 0 Gz exposure would be, were it possible to shift directly from 1 Gz without going through the 1.8-Gz phase. In this hypothetical case, one may calculate (Eq. 3), based on the available energy output at 1 Gz, that VT would increase to 1.066 liters at 0 Gz, considering only the changes in the mechanical properties. Assuming now a decrease in the energy output equal to that occurring when going from 1.8 to 0 Gz, the calculated VT at 0 Gz would be reduced to 0.939 liter. Finally, considering the mechanical properties occurring in the supine position, one would further reduce VT to 0.710 liter, a value similar to that measured in the supine posture (0.718 liter). This is in agreement with data on ventilatory response in sustained microgravity (12), although this comparison should be taken with reservation, as the metabolic level may not be the same.
Why the conditions of sustained microgravity and supine posture lead to reduction in ventilation remains to be explained. We wish to recall the hypothesis put forward by Anthonisen et al. (2) back in 1965. They reasoned that the relative hyperventilation in erect posture is based on gravity-dependent changes in brain perfusion: moving from supine to erect would cause a decrease in brain blood flow and a local brain tissue increase in CO2 partial pressure for the same metabolic demand. This would trigger a reflex hyperventilation that lowers alveolar CO2 pressure to increase brain-blood oxygenation (2).
It appears difficult to reconcile in a model the complex interaction between passive muscle properties (force-length), afferents of opposite sign (excitatory from spindles and inhibitory from tendon organs), differences in receptor stimulation threshold, and, possibly, volitional component in response to sudden changes in the mechanical properties of the respiratory system. It appears, however, that a compensatory reflex would readjust the overall muscle output so as to match the need of force generation to changing loads. This concept integrates the idea of "operational length compensation" (3), which proposes a readjustment of neural drive when the force-length characteristics have been modified.
It appears interesting to note a remarkable feature of the mechanical arrangement of the respiratory system. In fact, within the VT range, the changes in lung and chest wall elastic work are similar on changing the gravity vector, but, because the two structures operate in opposite directions, the resultant change in WI and in ventilation appears relatively buffered.
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ACKNOWLEDGMENTS |
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FOOTNOTES |
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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.
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This article has been cited by other articles:
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  R. C. Sa, G. K. Prisk, and M. Paiva Microgravity alters respiratory abdominal and rib cage motion during sleep J Appl Physiol, November 1, 2009; 107(5): 1406 - 1412. [Abstract] [Full Text] [PDF]
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); elastic work released by the chest wall (
); and net elastic work performed by the inspiratory muscles (
). Statistical significance relative to *1 Gz, 
1.8 Gz, 
0 Gz, and 
supine (P < 0.05). B: total elastic muscular inspiratory work as function of the total compliance of the respiratory system on changing Gz or posture. Data are expressed as means ± SE.
