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John Rankin Laboratory of Pulmonary Medicine, Department of Preventive Medicine, University of Wisconsin-Madison, Madison, Wisconsin 53705
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ABSTRACT |
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Top
Abstract
Introduction
Methods
Results
Discussion
References
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We subjected 29 healthy young women (age: 27 ± 1 yr) with a wide range of fitness levels [maximal oxygen
uptake (
O2 max): 57 ± 6 ml · kg
1 · min1;
35-70
ml · kg1 · min1]
to a progressive treadmill running test. Our subjects had significantly smaller lung volumes and lower maximal expiratory flow rates, irrespective of fitness level, compared with predicted values for age-
and height-matched men. The higher maximal workload in highly fit
(O2 max > 57 ml · kg1 · min1,
n = 14) vs. less-fit
(O2 max < 56 ml · kg1 · min1,
n = 15) women caused a higher maximal
ventilation (E) with increased tidal volume (VT)
and breathing frequency (fb) at
comparable maximal VT/vital
capacity (VC). More expiratory flow limitation (EFL; 22 ± 4% of
VT) was also observed during
heavy exercise in highly fit vs. less-fit women, causing higher
end-expiratory and end-inspiratory lung volumes and greater usage of
their maximum available ventilatory reserves.
HeO2 (79% He-21%
O2) vs. room air exercise trials
were compared (with screens added to equalize external apparatus
resistance). HeO2 increased
maximal expiratory flow rates (20-38%) throughout the range of
VC, which significantly reduced EFL during heavy exercise. When EFL was
reduced with HeO2, VT,
fb, and
E (+16 ± 2 l/min) were
significantly increased during maximal exercise. However, in the
absence of EFL (during room air exercise),
HeO2 had no effect on
E. We conclude that smaller lung
volumes and maximal flow rates for women in general, and especially
highly fit women, caused increased prevalence of EFL during heavy
exercise, a relative hyperinflation, an increased reliance on
fb, and a greater encroachment on
the ventilatory "reserve." Consequently,
VT and
E are mechanically constrained during
maximal exercise in many fit women because the demand for high
expiratory flow rates encroaches on the airways' maximum flow-volume
envelope.
expiratory flow limitation; ventilatory limitation; mechanical constraints; carbon dioxide elimination; hyperinflation; hypoxemia
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INTRODUCTION |
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Top
Abstract
Introduction
Methods
Results
Discussion
References
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THERE ARE IMPORTANT GENDER differences in resting pulmonary function (5) that might have an effect on the integrated ventilatory response and respiratory muscle work during exercise. Adult women consistently have smaller lung volumes and lower maximal expiratory flow rates even when corrected for standing height relative to men (5). Sitting height or differences in trunk length for the same standing height account for some, but not all, gender differences in lung volumes and maximal expiratory flow rates in teenagers and young adults (31). Mead (28) suggests that gender differences in pulmonary function can be explained by smaller-diameter airways relative to lung size, and these differences probably become significant relatively late in the growth period of the lung. Thurlbeck (33) found that mature men have a larger lung size brought about by a greater number of alveoli relative to that in mature women.
A substantial reserve exists for increases in ventilation in the young
to middle-aged normal, healthy untrained man, even at maximal exercise
(10, 14, 17). However, the endurance-trained man with a higher maximal
oxygen uptake (O2 max)
and CO2 production, producing a
high ventilatory demand, begins to approach the mechanical limits for
inspiratory and expiratory pressure and flow development (10, 20). As
the tidal exercise flow-volume loop reaches the boundary of the maximal
volitional loop and the tidal breath becomes progressively more flow
limited, endurance-trained men begin to increase their end-expiratory
lung volume (EELV), causing a less optimal length of the inspiratory
muscles for pressure generation (20). In addition, end-inspiratory lung
volume (EILV) begins to approach total lung capacity (TLC) because of
the rise in EELV and the large tidal volume
(VT). Recently, it was
determined that the decline in pulmonary function with normal aging
caused the older habitually trained adult to also show significant
expiratory flow limitation, relative hyperinflation, increased work of
breathing and, in some cases, a mechanical limit to ventilation at
maximal exercise (19, 27). Thus the effects of mechanical constraints of the lung on volumes and maximal expiratory flow rates become very
important to control of breathing during exercise in both the
endurance-trained male athlete and the habitually trained older adult
during high-intensity exercise.
We asked whether the smaller lung volumes and lower maximal expiratory flow rates in women relative to men would alter the degree of expiratory flow limitation and thereby affect the ventilatory response to exercise. We also questioned whether the increased ventilatory demands of a higher maximal workload in a highly fit woman would cause a different ventilatory response to exercise relative to that of a less-fit woman. Last, we used HeO2 breathing (79% He-21% O2) to increase the size of the maximal flow-volume envelope to examine the effects of reducing the mechanical constraints to airflow on the ventilatory response to exercise in women.
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METHODS |
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Top
Abstract
Introduction
Methods
Results
Discussion
References
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Twenty-nine female subjects, age 18-42 yr, were recruited to participate in the study. All except four of the subjects ran at least three times per week and averaged 32.5 miles/wk as a group (Table 1). All subjects' pulmonary function tests were within the normal predicted range (Table 2), and none had any history of cardiovascular or lung disease. None of the subjects was a smoker. All procedures were approved by the Human Subjects Committee Institutional Board of the University of Wisconsin-Madison. Informed consent was obtained in writing from each subject before testing.
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Resting Pulmonary Function Tests
Resting pulmonary function tests and exercise measurements were performed at the John Rankin Laboratory of Pulmonary Medicine. Vital capacity (VC), inspiratory capacity (IC), and forced expiratory volume in 1 s were determined by using a Collins 13.5-liter water-sealed spirometer (Warren E. Collins, Braintree, MA). Resting thoracic gas volume for the determination of functional residual capacity (FRC) was determined in a Collins body plethysmograph (22) by using Boyle's law. Residual volume (RV) was determined by using an inert gas with a single 10-s breath-hold dilution test (8).Flow, Volume, and Gas Measurements
All measurements have been described previously (27). Inspired and expired flow rates were measured separately by dual pneumotachographs (model 3800, Hans Rudolph). Volumes were determined by computer integration of the flow signals. Both flow signals were determined to be in phase up to 12 Hz. Volume calibration was performed for each inspiratory gas with various steady-state flows and verified by collecting in a calibrated tissot.The HeO2 gas was warmed and
humidified in a manner similar to that for room air. Mesh screens were
added to the inspiratory and expiratory tubing during the
HeO2 trial to attain identical external apparatus resistance with the ambient room air (79%
N2-21% O2) trial at flow rates from 0.5 to 9.0 l/s. Apparatus resistance was 0.80, 0.99, and 1.49 cmH2O · l1 · s
with room air and 0.90, 1.00, and 1.50 cmH2O · l1 · s
with HeO2 gas at flow rates of
3.1, 5.8, and 8.5 l/s, respectively. Thus with the added external
resistance the He effect was limited only to reducing the subjects'
internal airway resistance.
Inspired and expired gases were sampled at the mouth and in a mixing chamber via a mass spectrometer (model 1100, Perkin-Elmer), an Applied Electrochemistry model S-3A oxygen analyzer, and a Beckman Medical model LB-2 gas analyzer for measurement of CO2. All signals were sent through an analog-to-digital board (Techmar Labmaster; Scientific Solutions, Solon, OH) and sampled on a computer (PC Tailor 486 DX2/50) at 75 Hz.
Protocol
Each subject completed three exercise trials on the treadmill. For the initial exercise session, after a warm-up period (2-4 min), the first workload was set at 6 miles/h (mph), 0% slope, and was increased by 2 mph every 2.5 min until the subject reached a comfortable maximum speed (8 or 10 mph) for the remainder of the test. The incline was then raised 2% every 2.5 min until exhaustion. After a 20-min rest, the subjects repeated their highest workload for as long as possible to ensure that a plateau in oxygen uptake (O2) was achieved.
Following the criteria initially suggested by Taylor et al. (32), all
29 subjects were observed to have a plateau in
O2 max
(<150-ml increase in O2)
during the last two workloads. After the initial familiarization test,
subjects completed two single-blind progressive exercise tests (with
the same workloads as the initial test) on separate days, breathing either room air (n = 29) or a
HeO2 mixture
(n = 22), with a minimum of 48 h
between tests. All subjects were tested during the follicular phase of
the menstrual cycle as determined by progesterone levels (range:
0.2-1.3 ng/ml) and from self-reported basal temperature levels
over a 30-day period.
Measurement of Arterial Blood Gases, Lactate, pH, and Potassium
Before the room air trial, subjects had a 20-gauge indwelling plastic catheter placed in the radial or brachial artery under local 1% lidocaine anesthesia. Multiple arterial blood samples (3 ml) were drawn during rest and the last 30 s of each workload for measurement of PCO2, pH, lactate, and potassium. Blood gases and pH were analyzed by using electrodes (Radiometer ABL2; OSM 3) calibrated with tonometered blood of known PO2 and PCO2. Arterial blood gases were corrected for temperature changes during exercise as measured from a thermocouple (Mona-a-Therm 6500) placed intranasally into the lower one-third of the esophagus. Blood lactate concentration was analyzed by a YSI lactate analyzer (model 1500 Sport) calibrated with reference standards spanning the appropriate range of values (0-30 mmol/l). Plasma potassium was analyzed by an AVL electrolyte analyzer (series 9100). Progesterone was determined by radioimmunoassay (Endocrine Sciences, Tarzana, CA).Determination of Expiratory Flow Limitation
Each subject performed a minimum of 3-5 voluntary maximal flow-volume loop (MFVL) maneuvers during the room air and HeO2 trials before and immediately after exercise, with the largest loop being used for comparison with tidal breathing. A maximal IC measurement was obtained during the last 20 s of each 2.5-min workload. A mean of 10-20 tidal breaths taken at the end of each workload was averaged (by using a computer averaging program) to provide a representative tidal flow-volume loop for that workload. The EELV was determined by subtracting the maximal IC for each workload from the TLC as measured at rest (19). EILV was calculated as the sum of EELV plus VT. Flow limitation for each workload was computed as the percentage of the expiratory tidal flow-volume loop for each workload that intersected the expiratory boundary of the MFVL.Estimation of Maximal Ventilation Available During Exercise
Maximal ventilation available during exercise was estimated by using two methods. 1) The maximal voluntary ventilation (MVV) was calculated as 12 s of volitional maximal ventilatory effort extrapolated (multiplied by 5) to 1 min. 2) Maximal ventilatory capacity (Ecap)
was calculated for each subject on the basis of the relationship
between the MFVL and the tidal exercise flow-volume loop at maximum
exercise (21). By using the VT
and EELV at maximum exercise, maximal respiratory frequency
(fmax) was obtained as if the
subject had breathed exclusively along the inspiratory and expiratory
boundaries of the MFVL during the tidal breath. After the maximal
VT
(VTmax)
was divided into small increments (average: 20-40 ml), minimum
expiratory time was determined by dividing each volume increment by the
maximal expiratory flow within each volume segment and these times were
then summed over the expiratory phase of the
VT. In a similar manner, by
using the same volume increments and the maximal inspiratory flow,
minimum inspiratory time was calculated
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Prediction Equations
We selected prediction equations for resting lung function from cross-sectional studies that reflected the background of our subject population, namely, those that included both male and female subjects who were nonsmokers, Caucasian, and primarily US residents (9, 25).Statistical Analysis
We used paired t-tests with Bonferroni correction for multiple comparisons of pairs of mean values for actual vs. predicted pulmonary function variables and for room air vs. HeO2 breathing at specific work rates. Unpaired t-tests were used to compare mean values between highly vs. normally fit groups.| |
RESULTS |
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Top
Abstract
Introduction
Methods
Results
Discussion
References
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Resting Pulmonary Function Tests
The group mean values of the resting lung volumes and maximal flow rates are shown in Table 2. Mean TLC, VC, IC, and RV were 6-16% larger (P < 0.05) than predicted values for age- and height-matched women, with no significant differences in FRC and in all values of maximal expiratory flow rates. Compared with predicted values for men of comparable age and height, TLC, VC, IC, and all maximal expiratory flow rates were significantly smaller, whereas RV and FRC were significantly larger.Ventilatory and Lung Volume Response to Progressive Exercise
The ventilatory responses from rest through maximal exercise are shown in Figs. 1 and 2. During the progression from rest to moderate through heavier exercise, VT showed a progressive increase, as did breathing frequency. From heavy through maximal exercise, VT plateaued with the increased breathing frequency accounting for all of the increase in minute ventilation (E). VT/VC increased gradually
through heavy exercise and leveled off at 50-52% during heavy
through maximal exercise. There was a significant linear relationship
(r = 0.88) between VC and
VTmax
described by the following equation:
VTmax
(liters) = 0.527VC 
0.05. Dead space
volume/VT dropped significantly
from rest to moderate exercise, with a small further decrease through
maximal exercise. Alveolar ventilation increased progressively from
rest to moderate through maximal exercise.
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The arterial blood potassium, pH, lactate, and
PCO2
(PaCO2) values during progressive
exercise are shown in Fig. 3,
A and
B. There was a gradual increase in
potassium from rest to moderate through maximal exercise. Levels of
arterial blood pH and lactate were unchanged from rest to mild and
moderate exercise, followed by a progressive metabolic lactacidosis
during heavy and maximal exercise. Group mean
PaCO2 dropped significantly
from rest to mild exercise (~62% of
O2 max)
because 19 subjects showed an immediate significant drop (3.6 ± 0.3 Torr) and 10 exhibited an isocapnic response (0.2 ± 0.15 Torr). At maximal exercise, all 29 subjects showed a
significant hyperventilatory response (PaCO2: 3.0 to 9.0 Torr
from rest).
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Fitness Effects on Resting Lung Function, Ventilation, and Expiratory Flow Limitation During Exercise
Figure 4 shows individual values forO2 max plotted against
%predicted VC and %predicted maximal expiratory flow at 50% of VC
(MEF50) for all 29 subjects.
There was no significant correlation between %predicted
O2 max and
predicted values for any resting lung volumes or expiratory flow rates.
To determine whether there were fitness effects on ventilation and lung
volumes at maximal exercise, we divided the 29 subjects into highly fit
(O2 max > 57 ml · kg1 · min1,
n = 14) and less-fit
(O2 max < 56 ml · kg1min1,
n = 15) groups for comparison (Table
3). There were no significant differences
between groups in age, height, weight, resting lung volumes, or maximal
expiratory flow rates. Highly fit women had a significantly higher
maximal ventilation
(Emax),
accounted for by both a higher
VT and breathing frequency
(P < 0.05) at maximal exercise
compared with less-fit women. Highly fit women also had significantly
higher
Emax /Ecap,
EELV/TLC, and EILV/TLC compared with less-fit women.
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Ensemble-averaged tidal flow-volume loops for rest through maximal
exercise in highly fit and less-fit women are shown in Fig.
5. Expiratory flow limitation was minimal
or nonexistent in all subjects through moderate-intensity exercise.
Less-fit women showed minimal expiratory flow limitation during maximal exercise, but the significantly higher
Emax
in highly fit women was enough to produce considerable flow limitation
during high-intensity exercise. During heavy and maximal exercise, 12 of 14 in the highest-fitness group had significant expiratory flow
limitation, whereas only 4 of 15 showed flow limitation in the less-fit
group.
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Effect of the Available Maximal Flow-Volume Envelope on Exercise Ventilation and Lung Volumes
To determine whether expiratory flow limitation in women affected their ventilatory response and lung volumes during exercise, we used HeO2 breathing in 22 subjects to increase the size of the MFVL and, in turn, reduce the amount of expiratory flow limitation during exercise. The averaged MFVL with the ensemble-averaged rest and tidal exercise loops placed within the MFVL for the room air and HeO2 trials are shown in Fig. 6. HeO2 increased maximal volitional expiratory flow rates at 75, 50, and 25% of VC by 2.5, 1.7, and 0.6 l/s, respectively, compared with room air. At maximal exercise, mean expiratory flow limitation was significantly reduced (from 26 ± 5 to 5 ± 3% of VT) during HeO2 compared with room air breathing. Coincident with the reduction in expiratory flow limitation with HeO2 vs. room air, subjects also showed a significantly lower EELV and EILV at maximal exercise and a significant increase inE,
VT, and breathing frequency
(P < 0.05).
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Figure 7 compares the ventilatory response
in the room air vs. HeO2 trials at
the same workloads during progressive exercise in the 15 subjects who
showed significant expiratory flow limitation (range 19-78%
of VT) at one or
more work rates during the room air trial.
E was not significantly different
(P > 0.60) at comparable workloads
between the room air vs. HeO2
trials when subjects showed no expiratory flow limitation (
) during
the room air trial. However, HeO2
significantly increased breathing frequency,
VT, and
E (compared with room air)
(P < 0.01) only at workloads where
significant expiratory flow limitation occurred during the room air
trials. At these workloads, expiratory flow limitation averaged 38% of VT during room air breathing and
7% of VT during
HeO2 breathing.
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Figure 8 compares the ventilatory response
in the room air vs. HeO2 breathing
trials at the same workloads during progressive exercise in seven
subjects who did not show any expiratory flow limitation throughout the
room air trial. E was always similar during the room air vs. HeO2
trials when compared at the same workloads, and there was also no
significant difference in either EELV or EILV at maximal exercise
between the two trials.
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DISCUSSION |
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Top
Abstract
Introduction
Methods
Results
Discussion
References
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The purpose of this study was to determine whether the ventilatory response to heavy exercise in women is constrained by their smaller lung volumes and reduced capability of their airways for flow rate. The major findings in this study were that 1) the higher exercise capability and therefore ventilatory response in the highly trained women led to increased expiratory flow limitation and greater utilization of ventilatory reserve compared with less-trained women and 2) significant expiratory flow limitation in women constrained the ventilatory response during high-intensity exercise. The data obtained in our study, compared with published data in men, suggest that the relatively smaller lung volumes and lower maximal expiratory flow rates in women caused them to utilize a greater percentage of their ventilatory reserve during exercise.
Gender Comparisons of Resting Lung Function and the Ventilatory Response to Exercise
Prediction equations for lung function show a significant gender difference in adults (see review of lung function in Ref. 5). Height-matched men have larger-diameter airways (28), with larger lung volumes and diffusion surfaces (33) compared with women. Our findings support this generalization because our young female subjects had significantly smaller lung volumes and lower maximum expiratory flow rates compared with predicted values for men at the same age and standing height (Table 2). Some of these gender differences in resting lung function are partially explained by differences in sitting height, which may serve as a surrogate for chest volume (31).Typically, men demonstrate a large increase in VT and breathing frequency from mild to moderate exercise, followed by a plateau in VT from heavy to maximal exercise. We observed a similar response in women (Fig. 1). In addition, when the VTmax was equalized for VC (Table 3), the values for our female subjects were consistent with previously reported values in trained men (20) and with those of untrained men and women (23) (VTmax/ VC ~50%). Given this consistent ratio of VTmax to VC for both men and women, combined with the lower VC values in height-matched women (Table 2), we would therefore speculate that women would have a lower VTmax compared with men.
Because women are generally shorter than men, and because both gender
and height are important determinants of lung volumes and expiratory
flow rates (5), we would suggest two important differences in the
ventilatory response to exercise in women compared with men.
1) Given the similar
VTmax / VC
in both men and women, the smaller VC in women would also cause a
plateau at a lower VTmax. Thus
a woman would presumably need to rely on a higher breathing frequency
at any given E compared with a man during high-intensity exercise. 2) A woman
would also have lower maximal expiratory flow rates (5), creating a
smaller maximal flow-volume envelope. Thus a woman would be expected to
show significant expiratory flow limitation sooner (i.e, at a lower
E) or at a comparable Emax,
and more of the VT would be flow
limited. In addition, the increase in expiratory flow limitation in a
woman would increase EELV and EILV compared with a man.
We utilized both
Ecap
and MVV to estimate maximal available ventilation and observed
Emax / Ecap
and
Emax / MVV
in women, which often exceeded 80% at a
E of 110-120 l/min (Table 3). This suggests that at any comparable ventilation during
exercise, highly fit women would use a substantially greater portion
of their ventilatory reserve compared with that reported for
men (20). Eventually, a highly fit man approaches a similar
percentage of ventilatory capacity
(Emax / Ecap > 80%) but not until he reaches much greater levels of
O2 and
E than does a woman (20). Therefore, both
gender per se and height have an effect on lung volumes and maximal
flow rates, and each is an important determinant of the ventilatory
response to heavy exercise and of the proportion of maximal available
ventilation utilized.
Effect of Fitness on Flow Limitation and Lung Volumes During Exercise
The similar lung volumes and maximal expiratory flow rates among our subjects with a wide range inO2 max values (Fig. 4) are in agreement with studies demonstrating that neither fitness nor
habitual running and/or training has an effect on pulmonary function (20, 26, 29, 30). However, there is good evidence that very
young male and female swimmers (2, 4) and competitive adult male and
female swimmers (3, 7) have larger lungs compared with the normal
population.
We observed minimal amounts of expiratory flow limitation in the
less-fit women at maximal exercise
(Emax = 104 l/min) and, after the initial fall in EELV during moderate
exercise, EELV remained below resting FRC (Fig.
5A) throughout exercise. Presumably, the lower EELV maintained a more optimal length of the inspiratory muscles for pressure generation (17). In contrast, the higher Emax
(~113 l/min) in the highly fit women was sufficient to cause
significant expiratory flow limitation, which in turn caused EELV to
approach and exceed resting FRC during heavy and maximal exercise (Fig.
5B). Trained men also raise their
EELV when they experience significant expiratory flow limitation, but
because of their relatively larger MFVL they do not generally
experience this until ventilation exceeds 120 l/min (20). Therefore,
the combination of an increased ventilatory demand and a higher EELV from the greater prevalence of expiratory flow limitation in a highly
fit woman would presumably cause EILV to approach 90% of TLC. It has
been suggested that with trained young men (20), and especially with
trained older adults (19), the increase in elastic work incurred when
more of the tidal breath occurs at high lung volumes would preclude
reaching an EILV > 90% of TLC. Therefore, a small flow-volume
envelope and significant expiratory flow limitation caused a very high
EILV during heavy exercise in the highly fit women, and, to minimize
elastic work, further increases in
VT do not appear to be an
available option. Thus increasing breathing frequency (compared with
men) would seem to be the only strategy available to a highly fit woman
to attain the necessary ventilation to meet the metabolic needs of
high-intensity exercise.
Consequences of Expiratory Flow Limitation to Ventilatory Response
The purpose in comparing the HeO2 vs. room air trials was to determine the effects of increasing the size of the MFVL, thereby reducing expiratory flow limitation, on lung volumes and ventilation. We noted previously that EELV begins to rise in our subjects at the onset of significant flow limitation. However, with the reduction in expiratory flow limitation with HeO2 breathing, our subjects maintained a lower EELV (Fig. 5) and, despite a higher VT, had a lower EILV. Furthermore, the lower EELV in the HeO2 vs. room air trials, occurring only when HeO2 breathing significantly reduced flow limitation, provides additional evidence that expiratory flow limitation is the cause of the increase in EELV during heavy exercise.We believe this is the first study to use room air vs.
HeO2 trials to directly determine
the effects of flow limitation on the magnitude of the ventilatory
response during high-intensity exercise in either men or women. Other
studies have noted a higher ventilatory response during exercise with
HeO2 vs. room air, but none had
data on flow limitation that could be used to explain the differences.
At comparable workloads, our subjects had a higher E only when expiratory flow limitation
was reduced with HeO2 vs. room air
(Fig. 7), and E was unaffected by
HeO2 at workloads that did not
produce expiratory flow limitation during the room air trial (Figs. 7
and 8). Brice and Welch (6) also observed an unchanged
E during moderate exercise when comparing
room air vs. HeO2 and a
consistently higher E with
HeO2 breathing during heavy
exercise, but they did not determine expiratory flow limitation. They
speculated that the HeO2 effect on
ventilation did not occur during moderate exercise because both room
air and HeO2 flows were
essentially laminar, and it was only during high-intensity exercise
that the more laminar flows with
HeO2 breathing significantly decreased airway resistance. However, the similar
E (room air vs.
HeO2) in our subjects without
flow limitation, even during heavy exercise and at high flow rates
(Figs. 7 and 8), would suggest that E is
increased with HeO2 only when flow
limitation is reduced. Thus we have consistent evidence that even
relatively small amounts of expiratory flow limitation have an
inhibitory effect on the magnitude of the ventilatory response during
exercise. In contrast, Hussain et al. (18) observed an increased
ventilatory response with HeO2
breathing even during moderate exercise when flow limitation was highly
unlikely. However, these investigators were also reducing the external
apparatus resistance during HeO2
compared with room air breathing, which might explain the
HeO2 effect on ventilation at the
lower exercise workloads. We added external resistance during the
HeO2 trial to attain identical
external apparatus resistance to the room air trial. Importantly, we
were then able to narrow the scope of the
HeO2 effect to address only
changes in internal airflow resistance and expiratory flow limitation
on the ventilatory response.
Our results showing a marked effect of
HeO2 on the ventilatory response
during heavy exercise contrast with those using a proportional assist
ventilator (PAV) to "unload" the inspiratory muscles. Gallagher
and Younes (13) and Younes (34) observed no effect on exercise
ventilation even when the load on respiratory muscles was substantially
reduced via PAV; these authors speculated that the higher
E previously shown with
HeO2 breathing occurs because the
He replacement of N2 (in the
inspirate) is a stimulus to breathing. However, our data obtained both
within and among subjects strongly suggest that reducing flow
limitation is required for an HeO2
effect on exercise E. In contrast,
"unloading" with the PAV has no effect on the size of the maximal
flow-volume envelope and thus would only help to determine whether the
pressure generated by the respiratory muscles might constrain
ventilation. In contrast, HeO2
provides only a minimal pressure unloading effect on inspiratory muscles but has a substantial effect on the maximal flow-volume envelope. Accordingly, if the use of
HeO2 primarily evaluates the
effect of expiratory flow limitation on ventilation, then our findings
imply that flow limitation exerted a significant constraint on the
ventilatory response to heavy and maximal exercise in fit women.
Consequences of Flow Limitation to Ventilatory Work and Gas Exchange
The increased expiratory flow limitation and relative hyperinflation during heavy exercise in women likely resulted in an increased work and O2 cost of hyperpnea from a combination of factors. First, the smaller VC, resulting in a lower VTmax and therefore a higher breathing frequency in women, would increase the amount of dead space ventilation. Thus an even higher ventilation is necessary to obtain a similar alveolar ventilation as in men, which would result in a less efficient exercise hyperpnea. Second, a higher breathing frequency with a shortened expiratory time causes higher expiratory flow rates that increase the likelihood and the amount of expiratory flow limitation. Aaron et al. (1) noted that subjects with significant expiratory flow limitation had the highest O2 cost per liter ofE, presumably because of the increase in
expiratory resistance and turbulent airflow with more of the tidal
breath in a compressed, smaller-diameter airway. Third, the higher EELV
caused by the expiratory flow limitation would shorten the initial
length of the inspiratory muscles. Accordingly, Johnson et al. (20)
reported that the hyperinflation caused by the increases in flow
limitation had a significant effect on the fraction of total
inspiratory muscle capacity utilized and also caused a significant fall
in dynamic compliance at an EILV/TLC of 86%. The highly fit women,
with an EILV/TLC of 90% during heavy exercise, would likely have an
equal or greater fall in dynamic compliance, and thus an increased
elastic load on the inspiratory muscles over a greater portion of the
tidal breath. Overall, the less efficient hyperpnea and the higher
respiratory muscle O2 requirement
in a woman compared with a man would be expected to increase
respiratory muscle competition for blood flow and
O2, thereby possibly
compromising perfusion to the exercising limb locomotor muscles (15).
Despite the presumed higher work of breathing and associated
respiratory muscle O2 cost with
hyperinflation caused by the high expiratory flow limitation in a woman
during heavy exercise, all of our subjects showed a hyperventilatory
response that was adequate for CO2
elimination (PaCO2 < 38 Torr; Fig.
3B). In addition, there was no
correlation among our subjects between the amount of expiratory flow
limitation and the magnitude of their hyperventilatory response (data
not shown). However, we also found a high prevalence of
exercise-induced arterial hypoxemia (EIAH) during heavy exercise in our
female subjects, which correlated closely with an excessively widened
alveolar-arterial O2 difference
(16). From the alveolar air equation, we calculated that given the
excessively widened alveolar-arterial
O2 difference, ventilation at
O2 max would have to be
over 50 l/min higher to offset the EIAH in our female subjects. This
additional ventilation required would exceed both estimates of
ventilatory capacity (MVV and
Ecap)
in our female subjects. However, we cannot be sure that, even if the
mechanical constraints on flow limitation were removed, subjects would
"choose" to increase ventilation sufficiently to offset the EIAH.
For example, the increase in ventilation with
HeO2 at
O2 max (~16
l/min) (Fig. 6) is only about one-third of that required to completely offset the arterial hypoxemia. Accordingly, Dempsey et al. (12) observed in highly fit men that
HeO2 breathing significantly, but
not completely, attenuated the EIAH during high-intensity exercise.
Overall then, the smaller lung volumes and lower maximal flow rates
that create expiratory flow limitation in a fit, exercising woman
appear to constrain the capability of a highly fit woman to compensate
for an inadequate alveolar-to-arterial
O2 exchange, thereby exacerbating
the EIAH.
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ACKNOWLEDGEMENTS |
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We thank Drs. Glenn A. Nickele and William B. Nelson for medical assistance.
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FOOTNOTES |
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This work was supported by National Heart, Lung, and Blood Institute Grant HL-15469.
Address for reprint requests: J. A. Dempsey, 504 N. Walnut, Madison, WI 53705.
Received 10 July 1997; accepted in final form 11 February 1998.
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REFERENCES |
|---|
|
Top
Abstract
Introduction
Methods
Results
Discussion
References
|
|---|
1.
Aaron, E. A.,
B. D. Johnson,
C. K. Seow,
and
J. A. Dempsey.
Oxygen cost of exercise hyperpnea: measurement.
J. Appl. Physiol.
72:
1810-1817,
1992
2.
Andrew, G. M.,
M. R. Becklake,
J. S. Guleria,
and
D. V. Bates.
Heart and lung function in swimmers and nonathletes during growth.
J. Appl. Physiol.
32:
245-251,
1972
3.
Armour, J.,
P. M. Donnelly,
and
P. T. P. Bye.
The large lungs of elite swimmers: an increased alveolar number?
Eur. Respir. J.
6:
237-247,
1993[Abstract].
4.
Åstrand, P. O.,
L. Engstrom,
B. O. Eriksson,
P. Karlberg,
I. Nylander,
B. Saltin,
and
C. Thoren.
Girl swimmers: with special reference to respiratory and circulatory adaptation and gynecological and psychiatric aspects.
Acta Paediatr. Suppl.
147:
5-71,
1963.
5.
American Thoracic Society.
Lung function testing: selection of reference values and interpretative strategies.
Am. Rev. Respir. Dis.
144:
1202-1218,
1991[Medline].
6.
Brice, A. G.,
and
H. G. Welch.
Metabolic and cardiorespiratory responses to He-O2 breathing during exercise.
J. Appl. Physiol.
54:
387-392,
1983
7.
Clanton, T. L.,
G. F. Dixon,
J. Drake,
and
J. E. Gadek.
Effects of swim training on lung volumes and inspiratory muscle conditioning.
J. Appl. Physiol.
62:
39-46,
1987
8.
Comroe, J. H.,
R. E. Forster,
A. B. Dubois,
W. A. Briscoe,
and
E. Carlsen.
The Lung. Chicago, IL: Year Book, 1964.
9.
Crapo, R. O.,
A. H. Morris,
P. D. Clayton,
and
C. R. Nixon.
Lung volumes in healthy nonsmoking adults.
Clin. Respir. Physiol.
18:
419-425,
1982.
10.
Dempsey, J. A.
Is the lung built for exercise?
Med. Sci. Sports Exerc.
18:
143-155,
1986[Medline].
11.
Dempsey, J. A.,
L. Adams,
D. M. Ainsworth,
R. F. Fregosi,
C. G. Gallagher,
A. Guz,
B. D. Johnson,
and
S. K. Powers.
Airway, lung and respiratory muscle function during exercise.
In: Handbook of Physiology. Exercise: Regulation and Integration of Multiple Systems. Bethesda, MD: Am. Physiol. Soc., 1996, sect. 12, chapt. 11, p. 448-514.
12.
Dempsey, J. A.,
P. G. Hanson,
and
K. S. Henderson.
Exercise-induced arterial hypoxemia in healthy human subjects at sea level.
J. Physiol. (Lond.)
355:
161-175,
1984
13.
Gallagher, C. G.,
and
M. Younes.
Effect of pressure assist on ventilation and respiratory mechanics in heavy exercise.
J. Appl. Physiol.
66:
1824-1837,
1989
14.
Grimby, G.,
J. Bunn,
and
J. Mead.
Relative contribution of rib cage and abdomen to ventilation during exercise.
J. Appl. Physiol.
24:
159-166,
1968
15.
Harms, C. A.,
M. A. Babcock,
S. R. McClaran,
D. F. Pegelow,
G. A. Nickele,
W. B. Nelson,
and
J. A. Dempsey.
Respiratory muscle work compromises leg blood flow during maximal exercise.
J. Appl. Physiol.
82:
1573-1583,
1997
16.
Harms, C. A., S. R. McClaran, D. F. Pegelow, G. Nickele, W. Nelson, and J. A. Dempsey.
Exercise induced arterial hypoxemia in healthy young women.
J. Physiol. (Lond.) In
press.
17.
Henke, K. G.,
M. Sharatt,
D. Pegelow,
and
J. A. Dempsey.
Regulation of end-expiratory lung volume during exercise.
J. Appl. Physiol.
64:
135-146,
1988
18.
Hussain, S. N. A.,
R. L. Pardy,
and
J. A. Dempsey.
Mechanical impedance as determinant of inspiratory neural drive during exercise in humans.
J. Appl. Physiol.
59:
365-375,
1985
19.
Johnson, B. D.,
W. G. Reddan,
D. F. Pegelow,
K. G. Seow,
and
J. A. Dempsey.
Flow limitation and regulation of functional residual capacity during exercise in an aging population.
Am. Rev. Respir. Dis.
143:
960-967,
1991[Medline].
20.
Johnson, B. D.,
K. W. Saupe,
and
J. A. Dempsey.
Mechanical constraints on exercise hyperpnea in endurance athletes.
J. Appl. Physiol.
73:
874-886,
1992
21.
Johnson, B. D.,
P. D. Scanlon,
and
K. C. Beck.
Regulation of ventilatory capacity during exercise in asthmatics.
J. Appl. Physiol.
79:
892-901,
1995
22.
Johnson, B. D.,
K. C. Seow,
D. F. Pegelow,
and
J. A. Dempsey.
Adaptation of the inert gas FRC technique for use in heavy exercise.
J. Appl. Physiol.
68:
802-809,
1990
23.
Jones, N. L.,
L. Makrides,
C. Hitchcock,
T. Chypchar,
and
N. McCartney.
Normal standards for an incremental progressive cycle ergometer test.
Am. Rev. Respir. Dis.
131:
700-708,
1985[Medline].
24.
Jones, N. L.,
E. J. Moran,
R. H. T. Edwards,
and
D. G. Robertson.
Clinical Exercise Testing. Philadelphia, PA: Saunders, 1975.
25.
Knudson, R. J.,
M. D. Lebowitz,
C. J. Holberg,
and
B. Burrows.
Changes in the normal maximal expiratory flow-volume curve with growth and aging.
Am. Rev. Respir. Dis.
127:
725-734,
1983[Medline].
26.
Martin, D. E.,
and
D. F. May.
Pulmonary function characteristics in elite women runners.
Int. J. Sports Med.
8:
84-90,
1987.
27.
McClaran, S. R.,
M. A. Babcock,
D. F. Pegelow,
W. G. Reddan,
and
J. A. Dempsey.
Longitudinal effects of aging on lung function at rest and exercise in healthy active fit elderly adults.
J. Appl. Physiol.
78:
1957-1968,
1995
28.
Mead, J.
Dysanapsis in normal lungs assessed by the relationship between maximal flow, static recoil, and vital capacity.
Am. Rev. Respir. Dis.
121:
339-342,
1980[Medline].
29.
Newman, F.,
B. F. Smalley,
and
M. L. Thompson.
Effect of exercise, body and lung size on CO diffusion in athletes and nonathletes.
J. Appl. Physiol.
17:
649-655,
1962
30.
Reuschlein, P. S.,
W. G. Reddan,
J. Burpee,
J. B. L. Gee,
and
J. Rankin.
Effect of physical training on the pulmonary diffusing capacity during submaximal work.
J. Appl. Physiol.
24:
152-158,
1968
31.
Schwartz, J.,
S. A. Katz,
R. W. Fegley,
and
M. S. Tockman.
Sex and race differences in the development of lung function.
Am. Rev. Respir. Dis.
138:
1415-1421,
1988[Medline].
32.
Taylor, H. L.,
E. Buskirk,
and
A. Henschell.
Maximal oxygen intake as an objective measure of cardiorespiratory performance.
J. Appl. Physiol.
8:
73-80,
1955
33.
Thurlbeck, W. M.
Postnatal human lung growth.
Thorax
37:
564-571,
1982
34.
Younes, M.
Exercise and the respiratory mechanical load.
In: Respiratory Control, edited by D. F. Speck,
M. S. Dekin,
W. R. Revelette,
and D. T. Frazier. Lexington: The University Press of Kentucky, 1993, p. 231-234.
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