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J Appl Physiol 89: 1787-1792, 2000;
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Vol. 89, Issue 5, 1787-1792, November 2000

Effect of gravity on aerosol dispersion and deposition in the human lung after periods of breath holding

Chantal Darquenne1, Manuel Paiva2, and G. Kim Prisk1

1 Department of Medicine, University of California, San Diego, La Jolla, California 92093-0931; and 2 Biomedical Physics Laboratory, Université Libre de Bruxelles, 1070 Brussels, Belgium


    ABSTRACT
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES

To determine the extent of the role that gravity plays in dispersion and deposition during breath holds, we performed aerosol bolus inhalations of 1-µm-diameter particles followed by breath holds of various lengths on four subjects on the ground (1G) and during short periods of microgravity (µG). Boluses of ~70 ml were inhaled to penetration volumes (Vp) of 150 and 500 ml, at a constant flow rate of ~0.45 l/s. Aerosol concentration and flow rate were continuously measured at the mouth. Aerosol deposition and dispersion were calculated from these data. Deposition was independent of breath-hold time at both Vp in µG, whereas, in 1G, deposition increased with increasing breath hold time. At Vp = 150 ml, dispersion was similar at both gravity levels and increased with breath hold time. At Vp = 500 ml, dispersion in 1G was always significantly higher than in µG. The data provide direct evidence that gravitational sedimentation is the main mechanism of deposition and dispersion during breath holds. The data also suggest that cardiogenic mixing and turbulent mixing contribute to deposition and dispersion at shallow Vp.

aerosol bolus; cardiogenic mixing


    INTRODUCTION
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES

AEROSOL BOLUS INHALATIONS have largely been used to study deposition and mixing processes in specific volumetric regions of the lung (3, 4, 13, 19). Particles are transported in the respiratory tract by the carrier gas, and they deviate from the streamlines mainly by diffusion, sedimentation, and inertia. Of these mechanisms, sedimentation is the only mechanism that is directly affected by a change in the gravity (G) level. The deposition and dispersion of aerosol boluses inhaled in microgravity (µG) therefore differ from those inhaled in normal gravity (1G) because sedimentation plays a role in these processes. This has been shown by our group in previous studies (7, 8), in which aerosol bolus inhalations with no breath hold before the subsequent exhalation were performed in µG, 1G, and 1.6G. In these studies, both aerosol deposition (DE) and dispersion (H) increased with increasing G level, and this effect was more pronounced in the alveolar region of the lung than in the large airways.

In the present study, we performed bolus inhalations of 1-µm-diameter particles, followed by breath holds of various lengths, up to 5 s. The tests were performed on the ground (1G) and during short periods of µG aboard the NASA Microgravity Research Aircraft, to determine the extent of the role that gravity plays in DE and H during breath holds. We show that gravitational sedimentation is the principal mechanism of DE during breath holding. The data also suggest that cardiogenic mixing contributes to DE and H and that the effect is larger in the central airways than in the alveolar region.


    METHODS
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES

Equipment. Aerosol bolus data were collected with the same equipment used in previous studies (7, 8). The equipment is fully described elsewhere (7). Briefly, the system allowed injection of an aerosol bolus with a half-width of ~70 ml at a given point in the inhaled air by switching computer-controlled pneumatic valves. The measurements of aerosol concentration and flow rate were provided by a photometer (model 993000, PARI, GmbH) (25) and a pneumotachograph (Fleisch #1, OEM Medical), respectively. The system was heated to body temperature to prevent water condensation. A diffusion dryer was located between the photometer and the mouthpiece and removed water vapor from exhaled air to avoid condensation on the lenses of the photometer. Dry air was also forced through the photometer between tests to further dry the device.

Aerosol generation. The bolus tube was filled with aerosol containing monodisperse polystyrene latex particles (Duke Scientific). The particles were supplied in suspension (water), and the concentrate was diluted and dispensed via two Acorn II nebulizers (Marquest Medical Products). Before entering the bolus tube, the aerosol flowed through a heated hose and a diffusion dryer to remove water droplets.

The size of the spherical particles, as specified by the manufacturer, was 1.07 ± 0.014 µm (mean ± SD). Aerosol concentration was ~104 particles/cm3. The aerosol generated by the nebulizers was checked with a particle sizer (PCS-2000 Special, PALAS). Size analysis showed that the number of doublets was <5%. Because deposition values are similar for 1- and 2-µm-diameter particles in µG (6, 8), the presence of doublets should not greatly affect the measurements of DE in µG. In 1G, assuming all doublets deposit (which is unlikely), the measured deposition would be overestimated by, at most, 5%. No significant effect was found from possible electrical charges on the particles (7).

Data recording and analysis. A personal computer (IBM ThinkPad 360 CSE), equipped with a 12 bit A/D card (National Instrument, DAQ700) was used for data acquisition. Signals from the photometer, a G sensor, and the pneumotachograph were sampled at 100 Hz. We used the same custom-built software for the data acquisition as that used in previous studies (7, 8).

Data were collected on the ground and aboard the NASA Microgravity Research Aircraft. A typical flight consisted of a climb to an altitude of ~10,000 m, with the cabin pressurized to ~600 Torr. A "roller coaster" flight profile was then performed. The aircraft was pitched up at a vertical acceleration of ~1.6 head-to-foot acceleration (Gz) to a 45° nose-high attitude. Then the nose of the craft was lowered to abolish wing lift, and thrust was reduced to balance drag (thus maintaining µG). A ballistic flight profile resulted and was maintained until the aircraft nose was 45° below the horizon. In this manner, µG was maintained for ~27 s. The level of µG was within 0.03 G. A pullout averaging ~1.6 Gz was maintained for ~40 s, causing the nose to pitch up to a 45° nose-high attitude, and allowed the cycle to be repeated.

Subjects and protocol. Four healthy subjects participated in the study. These are the same four subjects that participated in the previous studies (6-8), and we retained their subject numbers for comparison purposes. Their relevant anthropometric data are listed in Table 1.

                              
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  		Table 1.   Anthropometric data

After a few normal breaths, the subject exhaled to residual volume (RV) to ensure a known lung volume starting point. As functional residual capacity (FRC) varies significantly with G level (10, 18), we chose to use the more stable RV as the starting point for the test breath. Although there is a small change in RV in µG (10), the effect on our measurements was small. The test breath consisted of an inspiration from RV to 1 liter above FRC at a flow rate of ~0.45 l/s, then a breath hold for a preselected time, which was followed by an expiration to RV, also at a flow rate of ~0.45 l/s. A flowmeter provided visual feedback to the subject. FRC refers to the seated 1G FRC of the subject and was fixed for all experiments on that subject. During the inspiration, an aerosol bolus of ~70 ml was introduced at two different penetration volumes (Vp = 150 and 500 ml). Vp was defined as the volume of air inhaled from the mode of the aerosol bolus to the end of the inhalation. Tests were performed with breath-hold times (tBH) of 0 (no breath hold), 3, and 5 s.

The protocol was repeated four times in µG and up to 8 times in 1G for each Vp and tBH. Reliable measurements of the exhaled bolus concentration were not possible during the hypergravity phase because of the high deposition occurring during the breath holds; therefore, no data from hypergravity are presented. Before the flight, data was collected at 1G using the same protocol as that used in µG. Measurements for Vp were 160 ± 27 and 520 ± 39 ml in µG and 150 ± 23 and 500 ± 29 ml in 1G. The measured tBH were 3.2 ± 0.2 and 5.2 ± 0.1 s in µG and 3.2 ± 0.1 s and 5.2 ± 0.1 s in 1G. The protocol was approved both by the Committee on Investigations Involving Human Subjects at the University of California, San Diego and by the Institutional Review Board at the NASA Johnson Space Center, Houston, TX.

Data analysis. For each bolus test, we calculated DE and H, as described in a previous paper by our group (7). Briefly, DE was calculated using the following equation
DE<IT>=1−</IT><FR><NU><IT>N</IT><SUB>ex</SUB></NU><DE><IT>N</IT><SUB>in</SUB></DE></FR> (1)
where Nin and Nex are the number of particles in the inspired and expired bolus, respectively. Nin and Nex were calculated from the integration of the aerosol concentration as a function of the respired air. The integration was only done when the concentration exceeded 5% of the maximal expired concentration to reduce error due to the noise of the signal. The effect of this is to provide clearly defined limits of integration for all data with no significant change in deposition (22).

On a graph of aerosol concentration as a function of the respired volume, the half-width is defined as the bolus width (in ml) between the two points of one-half the maximum concentration of the bolus. The change in half-width (H) reflects the aerosol dispersion and was obtained using the following equation
H<IT>=</IT>(H<SUP><IT>2</IT></SUP><SUB>ex</SUB><IT>−</IT>H<SUP><IT>2</IT></SUP><SUB>in</SUB>)<SUP><IT>0.5</IT></SUP> (2)
where Hin and Hex are the half-width of the inspired and expired boluses, respectively. Only the volumes at one-half the maximum concentration are required to compute Hin and Hex. Therefore, this computation is not influenced by the 5% cutoff level of the signal used in the deposition calculation.

Statistical analysis. Statistical analysis was performed using Systat version 5.0 (Systat, Evanston, IL). Measurements performed for the same experimental conditions with the same subject were not averaged before the statistical analysis was performed. Data were grouped in different categories determined by variables such as G level (µG and 1G), tBH (0, 3, and 5 s), Vp (150 and 500 ml), gender, and subject number. A two-way ANOVA was performed to test for differences between the chosen categorical variables. Post hoc testing using Bonferroni adjustment was performed for tests showing significant F ratios. Significant differences were accepted at the P < 0.05 level.


    RESULTS
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES

DE. Figure 1 shows the DE as a function of tBH in µG and 1G for Vp of 150 and 500 ml. Data are averaged over the four subjects. In µG, DE was independent of tBH for both Vps. In 1G, DE increased with increasing tBH. DE increased from 12% with no breath hold to 44% with 5-s breath hold for Vp = 150 ml and from 27 to 70% for Vp = 500 ml. Except for tBH = 0 s, DE in 1G was always greater (P < 0.05) than in µG at both Vps.


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  		Fig. 1.   Aerosol bolus deposition (DE). Data are means ± SE, averaged over 4 subjects, and plotted as a function of breath hold time (tBH). , Microgravity (µG); down-triangle, 1G. A: penetration volume (Vp) = 150 ml. B: Vp = 500 ml. * Significantly different (P < 0.05) from 1G data; + significant differences between different tBH in 1G.

Table 2 shows the DE values for each subject (means ± SE) at both Vps and G levels. Significant differences (P < 0.05) between µG and 1G are also shown. No significant differences were found between genders.

                              
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  		Table 2.   Mean deposition for each subject

H. Figure 2 shows the aerosol bolus H averaged over the four subjects for both G levels as a function of tBH for Vps of 150 and 500 ml. For Vp = 150 ml (Fig. 2A), no significant differences were found between G levels, except for tests performed with no breath hold, in which H was slightly higher in 1G than in µG. There was a significant increase in H (P < 0.05) between tBH = 0 and 3 s at both G levels. H increased by 58 ml in µG and by 28 ml in 1G. There were no significant differences in dispersion between 3- and 5-s or between 0- and 5-s breath holds.


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  		Fig. 2.   Aerosol bolus dispersion (H). Data are means ± SE, averaged over 4 subjects, and plotted as a function of tBH. A: Vp = 150 ml. B: Vp = 500 ml. , µG; down-triangle, 1G. * Significantly different (P < 0.05) from 1G; #, + significant differences between tBH in µG and 1G, respectively.

For Vp = 500 ml (Fig. 2B), H in µG after 3 s of breath holding was significantly higher than H with no breath hold but was not significantly different from H after 5 s of breath holding. The increase in H between tBH = 0 and 3 s was 59 ml. However, this increase is small compared with the increase in 1G, in which H increased significantly with tBH (Fig. 2B). H was also significantly higher in 1G than in µG in all cases. Data with no breath hold, shown in Figs. 1 and 2, have already been reported in previous studies (7, 8).

Table 3 shows the H values for each subject at both Vps and G levels. Significant differences (P < 0.05) between µG and 1G are also shown. No significant differences were found between genders.

                              
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  		Table 3.   Mean dispersion for each subject


    DISCUSSION
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES

DE. Although there were no differences between DE in µG and 1G for bolus inhalations performed without breath hold, DE in 1G was higher than in µG when a breath hold was included in the maneuver (Fig. 1). The difference between DE in 1G and µG, the gravity-dependent deposition (DE1G - DEµG), increases with increasing tBH as the residence time of the particles in the lung is increased. Gravity-dependent DE increases from 13% for a 3-s breath hold to 22% for a 5-s breath hold for Vp = 150 ml, and from 32% for a 3-s breath hold to 42% for a 5-s breath hold for Vp = 500 ml. For a given breath hold, gravity-dependent DE was greater at Vp = 500 ml than at Vp = 150 ml. This increase is consistent with the smaller dimensions of the airways at Vp = 500 ml; in the smaller airways, the particles have a smaller average distance to travel under the influence of gravitational forces before they can deposit, and their DE rate is therefore higher (12).

DE is usually attributed to three main mechanisms: inertial impaction, gravitational sedimentation, and Brownian diffusion. During the breath hold, as there is no airflow in the airways, inertial impaction cannot cause DE. Gravitational sedimentation and Brownian diffusion are therefore effective in 1G during the breath hold, but only Brownian diffusion in µG as sedimentation is absent. The differences in DE that we observed between µG and 1G for tests performed with 3- and 5-s breath holds are reflective of an increase in deposition by sedimentation.

In tests performed without a breath hold, the similar DE values measured at both G levels are probably because the residence time of the particles in the airways is sufficiently short, so that there is little DE by gravitational sedimentation. This implies that sedimentation has only small effects on DE for the Vp and particle size we studied when tests are performed without a breath hold. This is explained by a combination of two effects: a shallow Vp that allows the particles to probe mainly large airways (with a consequently low DE rate by sedimentation) and a short residence time for the particles as the bolus is inhaled toward the end of the inspiration phase and soon exhaled (7). Up to Vp = 120 ml, airways have a diameter >1 mm. At a flow rate of 0.45 l/s, particles will travel through that volume in ~0.25 s. During that time, 1-µm-diameter particles settle by ~8 µm, which is <1% of the airway diameter. Even for Vp = 500 ml, in which airway diameter is ~450 µm, particles will settle by only ~35 µm during their transport in the respiratory tract.

The intrinsic mobility of 1-µm-diameter particles due to Brownian diffusion (~13 µm in 1 s) is smaller than that due to gravitational sedimentation (~33 µm/s) (8). It is therefore unlikely that the similar DE that we measured both in µG and 1G with no breath hold is due to Brownian diffusion. These particles are too small to be significantly affected by inertial impaction. The inertia of 1-µm-diameter particles, as measured by their stopping distance (a measure of the distance traveled by the particles until they follow the new direction of the flow), is 6 µm in the trachea and decreases deeper in the lung (8). Therefore, inertial impaction is also unlikely to contribute greatly to DE.

Our data therefore suggest that, as well as the usual three DE mechanisms (inertial impaction, gravitational sedimentation, and Brownian diffusion), other mechanisms are likely to be significant contributors to the DE process. The physical motion of the heart generates an oscillating motion of air in the lungs, which results in an enhanced gas mixing in the airways (11, 24). This mixing is usually referred to as cardiogenic mixing. Scheuch and Stahlhofen (20) investigated the effect of cardiogenic mixing on aerosol bolus behavior. They performed bolus inhalations of 1-µm-diameter particles on a subject at rest and after exercise when the heart rate was increased by more than a factor of two. They showed that the motion of the heart considerably influences both H and DE and that the effect was more obvious at shallow Vps. In a study on acute hemodynamic responses to weightlessness in humans during parabolic flights, Lathers et al. (16) found no difference in heart rate between µG and 1G but did find a stroke volume that was significantly larger in µG than 1G. Thus we would expect cardiogenic mixing to be larger in µG than in 1G. At Vp = 150 ml, the bolus is likely to experience one heartbeat for tests performed with no breath hold and seven to eight heartbeats for tests performed with a 5-s breath hold. For Vp = 500 ml, the bolus will experience ~3 heartbeats for tBH = 0 and 9-10 heartbeats for tBH = 5 s. There was a steady, but insignificant, increase in DE in µG at Vp = 150 ml (Fig. 1A). This suggests that the effect of cardiogenic mixing on DE is small.

In µG, we would expect a lower DE compared with 1G because of the absence of gravitational sedimentation. On the other hand, on the basis of Scheuch and Stahlhofen's findings (20), we would expect a higher DE in µG than in 1G due to cardiogenic mixing [caused by the increase in stroke volume in µG (16)]. It appears that these two effects (removal of gravitational sedimentation and increase in cardiogenic mixing) cancel out when the tests are performed without a breath hold. The similar depositions measured in µG and 1G are, therefore, likely to be from different mechanisms.

Mixing generated by turbulent flow might also explain the similar DE measured in µG and 1G with no breath hold. Whereas Reynolds' number is too low to generate turbulence in the airways themselves (21), it has been shown that turbulence is generated in the upper respiratory tract (lips to glottis) for inspiratory flows as small as 0.1 l/s (9). The turbulence generated in that region propagates downstream as far as the sixth generation during quiet breathing (21). Li and Ahmadi (17) studied the influence of turbulence on particle DE in a two-dimensional model of the trachea and main bronchi. For 1-µm particles and a flow rate of 0.5 l/s, they reported a DE efficiency in these airways varying from 4 to 8% depending on the turbulence model they used. Simulation without turbulence led to DE efficiency <1%. They also reported no effect of gravity on DE efficiencies for particles <5 µm in diameter. Their results suggest that turbulence may also be a factor for the similar DE values we measured in µG and 1G with no breath hold.

Our data at 1G with no breath hold were compared with data from the literature. In a study on 79 healthy subjects, Brand et al. (3) obtained average DE values of 9.3, 13.6, 20.4, and 29.2% at Vp = 100, 200, 400, and 600 ml, respectively, using 0.84-µm-diameter particles. This gives approximate DE values of 12 and 25% at Vp = 150 and 500 ml, respectively. These values are in close agreement with the results of this study (12 and 27%). Others have occasionally shown lower values (1, 15). There is a possibility that DE was underestimated in some of these studies because of problems associated with the configuration of the aerosol bolus delivery system (22), because, at times, negative values for DE were reported (4). The lower values obtained by Anderson et al. (1) are likely due to the larger end-inspiratory volume in their study (90% of total lung capacity) compared with the end-inspiratory volume in our study (FRC + 1 liter).

H. Aerosol bolus H has been largely used to probe convective mixing at different depths within the lung. Particles with a diameter of 1 µm have negligible diffusive properties compared with gases and are, therefore, well suited to trace convective gas transport. If aerosol bolus H was only due to mixing induced by inhaled and exhaled flows, there should be no difference in H between tests performed for the same Vp with different tBH, as there is no gas flow during the breath hold. The increase in H with increasing tBH (Fig. 2), especially in 1G, shows that mechanisms other than inhaled and exhaled flow contribute to aerosol bolus H.

The changes in both aerosol DE and H as functions of tBH were qualitatively similar at the higher Vp for both G levels (Figs. 1B and 2B). However, there was a clear dissociation between DE and H in the large airways. Gravity clearly affects DE (Fig. 1A), whereas it has little or no effect during breath hold on H (Fig. 2A). Gravitational sedimentation causes particles to settle within the airways and eventually to deposit. Because of this mechanism, particles that remain airborne at the end of the breath hold have a different radial position in the airways than at the beginning of the breath hold. Therefore, these particles follow different streamlines during expiration than during inspiration, resulting in the spreading of the exhaled bolus (higher H). At the higher Vp, this effect is sufficiently large that there are significant differences in H between µG and 1G at each tBH (Fig. 2B). At Vp = 500 ml, the airways are fully alveolated, and particles can settle either in or close to the alveoli, in which the flow is much smaller than in the adjacent airways (5), thus contributing even more to the spreading of the aerosol bolus.

In µG, because sedimentation is absent, only the mechanisms of cardiogenic mixing and diffusion remain to explain the increase in H we observed with increasing tBH. The Brownian displacements of 1-µm-diameter particles are small (~13 µm in 1 s) (2). The direct effect of diffusion on H is therefore small; H measured at the mouth during expiration would be expected to increase by <1 ml because of axial diffusion for both tBH = 3 and 5 s at a Vp of 150 ml. For Vp = 500 ml, H would increase by ~15 ml for tBH = 3 s and by ~25 ml for tBH = 5 s. These calculations are based on the Weibel symmetric model of the lung (23) for a lung volume of 4 liters. Radial diffusion may also affect the measured H; because of a change in the radial position, particles follow different streamlines during expiration than during inspiration, resulting in the spreading of the exhaled bolus. This effect is similar to that resulting from the sedimentation of the particles. Although the intrinsic motions of the particles due to diffusion are smaller than those due to sedimentation, it is hard to quantify the diffusive effect compared with the gravitational one because diffusion acts in all directions, whereas sedimentation occurs only in the direction parallel to the gravity vector. It is, however, unlikely that the increase in H we saw with increasing tBH can be explained solely by the diffusive properties of the particles.

The increase in H observed in µG (Fig. 2) is, therefore, likely due to cardiogenic mixing. In a study of cardiac action on gas mixing in dog lungs, Horsfield et al. (14) suggested that the flow pulsations resulting from the heart motions increased the effective diffusion coefficient in the conducting airways, whereas mixing in the distal part of the lung was only slightly affected. They explained the increase in mixing in the central airways as simply the result of the mechanical action of the heart. Scheuch and Stahlhofen (20) also showed that the motion of the heart considerably influences both aerosol DE and H and that the effect was more obvious at shallow Vps. The effect of cardiogenic mixing on aerosol H may be characterized by the slope of the linear regression of H as a function of tBH in µG. We found a slope of 15.3 ml/s for Vp = 150 ml (r2 = 0.97) and 9.1 ml/s for Vp = 500 ml (r2 = 0.58). The smaller slope at Vp = 500 ml suggests a smaller effect of cardiogenic mixing on aerosol H at this Vp, which is in agreement with previous studies (20).

Because of the exceptional environment in which the study was performed, the number of subjects was limited. Whereas the quite small number of data points provides ample information for a general qualitative assessment of the effect of gravity, one should be cautious when extrapolating the data to a larger population, even though it is clear that the effect of cardiogenic mixing is small.

Effect of altitude. Two flights were performed to collect all the data. During each flight, we were able to collect data at 1G before the start of the first parabola and after the end of the last parabola. There were no statistical differences between the bolus parameters computed from the data obtained in the plane at 1G and on the ground. This means that the lower barometric pressure in the aircraft did not significantly affect our measurements and that we can valuably compare aircraft and ground data.

In summary, aerosol bolus inhalations performed with 1-µm-diameter particles on the ground and during short periods of µG showed a clear dissociation between DE and H at shallow Vp. Although sedimentation did not affect aerosol H at a penetration volume of 150 ml, it clearly affected DE. At high Vp, both DE and H were affected by gravity, likely because sedimentation causes particles to cross streamlines and to move close to the airway walls, where exhaled flow velocities are small. The data also suggest that cardiogenic mixing contributes to aerosol H and DE. Although limited, the effect of cardiogenic mixing was larger in the central airways than in the periphery of the lung. This implies that the effect of cardiac motion in the lungs should be considered in future models of aerosol transport in the human lung, especially at shallow Vps.


    ACKNOWLEDGEMENTS

We acknowledge the collaboration of Janelle Fine, Jeff Struthers, Bob Williams, and Noel Skinner and the administrative assistance of Mary Murrell and Marsha Dodds. We also thank Sylvia Verbanck for scientific support and technical assistance in the size analysis of the aerosol.


    FOOTNOTES

This work was supported by NASA Grant NAGW 4372 and Program PRODEX (Belgium). C. Darquenne is a Parker B. Francis fellow in Pulmonary Research.

Address for reprint requests and other correspondence: C. Darquenne, Physiology/NASA Laboratory 0931, 9500 Gilman Dr., La Jolla, CA 92093-0931 (E-mail: cdarquenne{at}ucsd.edu).

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

Received 24 March 2000; accepted in final form 11 June 2000.


    REFERENCES
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES

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J APPL PHYSIOL 89(5):1787-1792
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