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John Rankin Laboratory of Pulmonary Medicine, Department of Preventive Medicine, University of Wisconsin-Madison, Madison, Wisconsin 53706
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ABSTRACT |
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 TOP
 ABSTRACT
 INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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We determined the role of expiratory flow
limitation (EFL) on the ventilatory response to heavy exercise in six
trained male cyclists [maximal
O2 uptake = 65 ± 8 (range
55-74)
ml · kg
1 · min1]
with normal lung function. Each subject completed four progressive cycle ergometer tests to exhaustion in random order: two trials while
breathing
N2O2
(26% O2-balance
N2), one with and one without added dead space, and two trials while breathing
HeO2 (26%
O2-balance He), one with and one
without added dead space. EFL was defined by the proximity of the tidal
to the maximal flow-volume loop. With
N2O2
during heavy and maximal exercise,
1) EFL was present in all six
subjects during heavy [19 ± 2% of tidal volume
(VT) intersected the maximal
flow-volume loop] and maximal exercise (43 ± 8% of
VT),
2) the slopes of the ventilation
(
E) and
peak esophageal pressure responses to added dead space (e.g.,
E/PETCO2, where PETCO2 is end-tidal
PCO2) were reduced relative to
submaximal exercise, 3)
end-expiratory lung volume (EELV) increased and end-inspiratory lung
volume reached a plateau at 88-91% of total lung capacity, and
4)
VT reached a plateau and then
fell as work rate increased. With
HeO2 (compared with N2O2)
breathing during heavy and maximal exercise,
1)
HeO2 increased maximal flow rates
(from 20 to 38%) throughout the range of vital capacity, which reduced
EFL in all subjects during tidal breathing, 2) the gains of the ventilatory and
inspiratory esophageal pressure responses to added dead space increased
over those during room air breathing and were similar at all exercise
intensities, 3) EELV was lower and
end-inspiratory lung volume remained near 90% of total lung capacity,
and 4)
VT was increased relative to
room air breathing. We conclude that EFL or even impending EFL during heavy and maximal exercise and with added dead space in fit subjects causes EELV to increase, reduces the
VT, and constrains the increase in respiratory motor output and ventilation.
dead space; helium-oxygen; feedback inhibition; respiratory muscle loading/unloading
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INTRODUCTION |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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THE HYPERVENTILATORY response to high-intensity
exercise has been attributed to one or more neurohumoral stimuli (4, 6, 16). There is also some indirect evidence that these ventilatory responses may be influenced by the mechanical constraints presented by
the airways and/or inspiratory muscles, at least in many highly fit
subjects capable of achieving higher than normal maximal metabolic rates and minute ventilations
(E) (17,
28). Significant amounts of expiratory flow limitation during moderate
through maximal exercise have been observed in highly fit healthy
subjects, including young and elderly adult men and women (13, 17, 28, 32). Tidal volume (VT) has
also been shown to reach a plateau and to fall as work intensity and
ventilation increase during heavy exercise (6, 8). Furthermore,
ventilatory responses to added inspired
CO2 or hypoxia are reduced in
slope during heavy exercise compared with light- to moderate-intensity
exercise (4, 17). These reductions in the ventilatory response to
superimposed chemical stimuli occurred during very high work rates,
where the expiratory portion of the tidal flow-volume loop intersected
the maximal flow-volume envelope, the end-expiratory lung volume (EELV) was increasing, and pressure generated by the inspiratory muscles often
exceeded 80% of the maximal dynamic capacity of the inspiratory muscles for pressure generation (17).
We asked whether the expiratory flow limitation incurred at high levels
of E may have
been responsible for the reduced ventilatory response to chemical
stimuli. We studied highly trained subjects who experienced significant
expiratory flow limitation during heavy exercise and used dead space
breathing as a means of increasing the chemoreceptor drive to breathe
(29, 36). We also used a low-density
HeO2 inspirate to reduce airway
flow resistance to increase the maximal available flow-volume envelope
and thereby eliminate expiratory flow limitation during tidal
breathing. This approach allowed us to determine whether expiratory
flow limitation and its associated effects on EELV and end-inspiratory
lung volume (EILV) were responsible for any observed changes in the
ventilation and breathing pattern in response to increasing exercise
intensity and superimposed chemical stimuli.
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METHODS |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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Six competitive male cyclists [maximal
O2 uptake
(O2 max) = 65 ± 8 ml · kg1 · min1]
were recruited to participate in the study. Pulmonary function tests of
all subjects were within the normal predicted range (Table 1), and no subject had any history of
cardiovascular or lung disease. All procedures were approved by the
Human Subjects Committee Institutional Board of the University of
Wisconsin-Madison, and informed consent was obtained. The physical
characteristics of the subjects (means ± SD) were as follows: age = 34 ± 16 yr, height = 1.73 ± 0.10 m, weight = 74.5 ± 3.9 kg.
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Resting pulmonary function tests. Vital capacity (VC), inspiratory capacity (IC), and forced expiratory volume in 1 s were determined using a water-sealed spirometer (model 13.5L, Warren E. Collins, Braintree, MA). Resting thoracic gas volume for the determination of functional residual capacity (FRC) was determined using Boyle's law in a Collins body plethysmograph (20). Total lung capacity (TLC) was calculated as the sum of the FRC measurement from the body box and the IC from spirometry. Residual volume was determined using an inert gas with a 10-s breath-hold dilution test (5).
Flow, volume, pressure, 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. Volume calibration was performed for each inspiratory gas with various steady-state flows and verified by brief collections in a calibrated Tissot instrument.
Esophageal pressure (Pes) was measured with a 10-cm latex balloon positioned in the lower one-third of the esophagus. Mouth pressure and Pes were connected to a Validyne transducer (model MP45-871, ±300 cmH2O). Pressure and flow signals were determined to be in phase up to 12 Hz. Inspired and expired gases were sampled at the mouth and in a mixing chamber via an O2 analyzer (model S-3A, Applied Electrochemistry) and a CO2 analyzer (model LB-2, Beckman). All signals were sent through an analog-to-digital board (Techmar Labmaster PGH, Scientific Solutions, Solon, OH) and sampled on a computer (PC Tailor 486 Dx2/50) at 75 Hz.Protocol.
Each subject completed an initial progressive incremental exercise test
on an electromagnetically braked cycle ergometer (Elma). After a
warm-up period (2-4 min), the first workload was set at 150-250 W (~40-50% of
O2 max) with an
increase of 50 W every 2.5 min until exhaustion. After a 20-min rest,
the subjects repeated their highest workload for as long as possible to
ensure a plateau in O2 uptake.
With use of the criteria initially suggested by Taylor et al. (37), all
six subjects were observed to reach a plateau in
O2 max (<150-ml
increase in O2) during the last two workloads. After the initial test, four progressive exercise tests
were conducted on separate days, with a minimum of 48 h between tests.
Each progressive test utilized the last six workloads of the initial
test. The following test conditions were applied in random order:
1)
N2O2
(26% O2-balance
N2) with no added dead space,
2)
N2O2
with 1 liter of dead space, 3)
HeO2 (26%
O2-balance He) with no added dead
space, and 4)
HeO2 with 1 liter of dead space.
We used 26% O2 in the inspirate
for all conditions to prevent hypoxemia during rebreathing of added
dead space. As measured by ear oximeter (model 47201A,
Hewlett-Packard), the range in Hb saturation was 96.7 ± 0.3 to 98.2 ± 0.4% during all four trials.
Added dead space and apparatus resistance. During the added dead space trials, subjects breathed through a piece of tubing placed between the mouthpiece and the Hans Rudolph valve. Measured by water displacement, the total dead space of the added section of tubing was 870 ml and the valve dead space was 115 ml.
The HeO2 and N2O2 mixtures were warmed and humidified. Mesh screens were added to the inspiratory and expiratory tubing during the HeO2 trial to attain external apparatus resistance identical to that during the N2O2 trial. Apparatus resistance was 0.80, 0.99, and 1.49 cmH2O · l1 · s
during the
N2O2
trials and 0.90, 1.00, and 1.50 cmH2O
· l1 · s
with HeO2 at flow rates of 3.1, 5.8, and 8.5 l/s, respectively. Thus, with the added external
resistances, the He effect was limited only to reducing the subject's
internal airway resistance. A piece of tubing identical in length and
resistance was added to the inspiratory and expiratory lines during the
trials in which no dead space was added to maintain comparable circuit
resistance relative to the trials in which dead space was added.
Determination of expiratory flow limitation. Each subject performed a minimum of three to five voluntary maximal flow-volume loop (MFVL) maneuvers during the N2O2 and HeO2 trials before and immediately after exercise, with the largest loop accepted. A maximal IC measurement was obtained during the last 20 s of each 2.5-min workload. Acceptable IC trials during exercise required that peak inspiratory Pes match that obtained at rest. A mean of 10-20 tidal breaths taken at the end of each workload were averaged (using a computer averaging program) to provide a representative tidal flow-volume and pressure-volume loop for that workload. The EELV was determined by subtracting the maximal IC for each workload from the TLC as measured at rest (20). EILV was calculated as the sum of EELV and 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 maximal flow-volume loop. We used the peak Pes obtained during the maximal IC maneuver to estimate the capacity of the inspiratory muscles to generate pressure (Pcap,i) for each workload.
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 subjects who were of the same age, did not smoke, were Caucasian, and resided primarily in the United States (1).
Statistical analysis.
All comparisons between group mean values and response slopes were
evaluated using a Friedman repeated-measures ANOVA on ranks. Student-Newman-Keuls post hoc test was used to determine where differences occurred. Significance for all tests was set at
P 
0.05.
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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 1. All values for lung volumes and flow rates were not different (P > 0.05) from predicted values for age- and height-matched men.
Ventilatory response to exercise and added dead space.
Figure 1 shows the ventilatory response to
progressive exercise. With
N2O2
breathing, there was a linear increase in
E with increasing work rate during submaximal exercise and hyperventilation during heavy and maximal exercise. Table 2
shows the response slopes of
E and the
nadir of inspiratory pressure to added dead space all expressed per
Torr change in end-tidal PCO2 (PETCO2). The slope of
the ventilatory response to added dead space
(E/PETCO2)
was similar during the first four workloads of
N2O2
but was significantly reduced during heavy and maximal exercise
(Table 2, Fig. 1).
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Breathing pattern and lung volume response to exercise and added
dead space.
The breathing pattern during progressive exercise is shown in Fig.
2 and the lung volumes in Fig.
3. During
N2O2
breathing without and with added dead space, there was a progressive
parallel increase in breathing frequency and
VT during submaximal exercise (Fig. 2). During heavy exercise,
VT reached a peak and then fell at maximal exercise during
N2O2
breathing (Fig. 2B), with breathing frequency accounting for all the increases in
E. EELV was
reduced at the onset of exercise, was maintained at these reduced
levels during moderate-intensity submaximal exercise, and then rose
during heavy and maximal exercise to approximate resting FRC
(Fig. 3A). EILV showed a
progressive increase during submaximal exercise, eventually reaching a
plateau at 89- 91% of TLC during heavy and maximal exercise
(Fig. 3B).
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Expiratory flow limitation during exercise.
Ensemble-averaged tidal flow-volume loops for rest and submaximal (74%
of O2 max), heavy (95%
of O2 max), and maximal exercise, along with the postexercise maximal voluntary flow-volume loop during
N2O2
breathing with and without added dead space are shown in Fig.
4A.
Expiratory flow limitation was nonexistent in all subjects without and
with added dead space through the first three workloads. Without added
dead space, all six subjects showed significant expiratory flow
limitation during heavy (19 ± 2% of VT) and maximal exercise
(43 ± 8% of
VT), when
E exceeded 120 l/min. With the increased ventilatory response to added dead space, four subjects showed significant expiratory flow limitation during the
fourth workload (12 ± 4% of
VT) and all six subjects
showed significant expiratory flow limitation during heavy (36 ± 9% of VT) and maximal
exercise (45 ± 7% of VT).
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Pes/PETCO2) during
submaximal exercise, and these response slopes were reduced during
heavy and maximal exercise (Table 2, see Fig. 6).
Effect of the available maximal flow-volume envelope on expiratory
flow limitation during exercise.
We used HeO2 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 rest
and submaximal (74% of O2 max), heavy (95% of
O2 max), and
maximal exercise loops placed within the MFVL for the
HeO2 trials are shown in Fig.
5A. HeO2 significantly increased
maximal volitional expiratory flow rates at 75, 50, and 25% of VC by
2.7, 2.7, and 0.9 l/s, respectively, compared with
N2O2.
Throughout exercise, expiratory flow limitation was nonexistent in all
subjects with no added dead space. With added dead space, there was
some measurable, but minimal, expiratory flow limitation during
HeO2 breathing in three subjects
(10 ± 14% of VT) only at
maximal exercise. Thus HeO2
eliminated or significantly reduced expiratory flow limitation during
heavy and maximal exercise relative to
N2O2
(Fig. 4A).
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Effect of reducing expiratory flow limitation via
HeO2 on ventilation, breathing pattern, and
lung volume response to exercise and added dead space.
The ventilatory response was unaltered with
HeO2 relative to
N2O2
breathing during the same submaximal exercise workloads up to 85% of
O2 max. At heavy
workloads with HeO2 breathing, further hyperventilation occurred (i.e., increased
E/CO2
output ratio and decreased
PETCO2) because of a higher
VT and breathing frequency
(Figs. 1 and 2). With
HeO2 breathing, the ventilatory
response slope to added dead space
(E/PETCO2; Fig. 1, Table 2) was unchanged and similar to that
with
N2O2 breathing over the first four workloads. At heavy and maximal exercise
intensities, the mean ventilatory response to added dead space with
HeO2 breathing was reduced
slightly but not significantly (P > 0.05) compared with lower workloads and was greater than the response
slope during heavy and maximal exercise with
N2O2 breathing (Table 2, Fig. 1). The increased
E/PETCO2 response with added dead space during heavy and maximal exercise with
HeO2 vs.
N2O2
breathing was entirely due to an increased gain in breathing frequency
(data not shown).
E exceeded 130-140 l/min. These higher
VT values during
HeO2 breathing (with no added dead
space and with added dead space) in heavy and maximal exercise occurred
because EELV remained reduced and below FRC rather than increased (as
occurred during
N2O2
breathing), whereas EILV remained at ~90% of TLC and unchanged from
that during
N2O2 breathing.
Ensemble-averaged tidal pressure-volume loops for submaximal, heavy,
and maximal exercise and the slope of the
Pes/PETCO2 during
HeO2 with and without added dead
space are shown in Fig. 5B. With
increases in exercise intensity, added dead space caused a substantial
decrease in peak inspiratory pressures. The slope of maximal
inspiratory pressure to added dead space
(Pes/PETCO2) was not
significantly different during submaximal, heavy, and maximal
exercise with HeO2 (Table 2,
Fig. 6). Thus, similar to the gain of the
ventilatory response with HeO2
breathing, the slope of maximal inspiratory pressure to added dead
space remained unchanged with increasing exercise intensity and during
heavy and maximal exercise was significantly higher than with heavy and
maximal exercise during
N2O2
breathing (Table 2). Peak tidal expiratory Pes increased
proportionately with increasing exercise intensity, although added dead
space had little effect on expiratory Pes during
HeO2 breathing at any workload
(Fig. 5).
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Ratings of dyspnea.
During the
N2O2
and HeO2 breathing with or without
added dead space, dyspnea ratings increased slightly and progressively over the initial three workloads and then more steeply approached a
maximal rating of 9-10 during heavy and maximal exercise
intensities (Fig. 7). Added dead space
caused increased dyspnea ratings at most workloads coincident with an
increasing PETCO2, E, and
expiratory flow limitation, and this occurred with
N2O2 and HeO2 breathing. Dyspnea
ratings at a specific workload and with or without added dead space
were not significantly influenced by
HeO2 breathing, even though
E was higher
and flow limitation was reduced during the
HeO2 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 mechanical
constraints affected the ventilatory response and breathing pattern of
heavy exercise. In the presence of significant expiratory flow
limitation during heavy and maximal exercise, we observed an attenuated
ventilation and reduction in the nadir of inspiratory Pes in response
to added dead space relative to that obtained during submaximal
exercise. With the removal of expiratory flow limitation via
HeO2 breathing, the gain of the
ventilatory response to added dead space was maintained throughout all
exercise intensities. Further comparisons of
N2O2
to HeO2 trials revealed that
1) when expiratory flow limitation
was reduced with HeO2 (heavy and
maximal exercise),
E was
increased, but
E was not
affected by HeO2 at submaximal
workloads where no expiratory flow limitation was observed during the
N2O2
trial; 2)
HeO2 reduced expiratory flow limitation during heavy and maximal exercise and reduced EELV with no
effect on EILV; thus the reduced EELV with
HeO2 prevented the fall in
VT during heavy and maximal
exercise; and 3)
HeO2 increased the gain of the
reduction in peak inspiratory Pes with added dead space during heavy
and maximal exercise. We believe that these correlative findings,
together with the observed effects of the
HeO2 breathing, demonstrate that
the occurrence of expiratory flow limitation, even when less than
one-half of the VT is flow limited, is an important determinant of EELV,
VT, and respiratory motor output
and ventilation during heavy exercise.
Measurement of flow limitation. We used the proximity of the tidal breath to the maximal voluntary flow-volume loop (obtained immediately after exercise) to estimate the onset and degree of expiratory flow limitation incurred during exercise. During voluntary forced expiratory maneuvers, pleural pressures (Ppl) are sufficiently high so as to compress intrathoracic gas, and when flow rate and volume are measured at the airway opening (as we did), this "external" measurement of volume displacement will underestimate the true dimensions of the maximal expiratory flow-volume envelope (15). Accordingly, we may have overestimated the onset and/or magnitude of expiratory flow limitation during exercise. On the other hand, previous studies utilizing an independent measurement of the maximal effective transpulmonary pressure (Pmax) during expiration showed close agreement during heavy and maximal exercise between the degree of expiratory flow limitation as estimated from the tidal vs. maximal flow-volume envelope with that determined from the proximity of the tidal expiratory pressure to the Pmax (9, 17, 30). Furthermore, the expiratory Pes values we observed during heavy and maximal exercise were in excess of 20 cmH2O over a significant portion of expiration, and these values were previously shown to approximate Pmax in normal subjects (19, 30). We believe, then, that our measurements of the proximity of the tidal to the maximal voluntary flow-volume envelope are reasonably accurate estimates of significant expiratory flow limitation, especially during heavy and maximal exercise, where the tidal flow-volume envelope showed time and volume courses similar to the voluntary maximal flow-volume loop with which they were compared (9, 17, 34).
Nonetheless, our estimates did not identify true flow limitation in the classic sense, i.e., demonstrate a further change in transpulmonary pressure with no increase in expiratory flow rate (22). Indeed, as explained below (see Flow "limitation" and its compensatory responses are on a continuum), during heavy exercise there appeared to be many more instances where maximal expiratory flow and pressure were achieved over only a portion of the VT range at low lung volumes. We believe that these instances of "impending" complete flow limitation have substantial significance in the regulation of EELV and exercise hyperpnea.Effects of expiratory flow limitation.
Many studies have utilized an added chemical stimulus to examine the
control of ventilation during exercise (4, 8, 17, 29, 33, 36). The
significant ventilatory response we observed to added dead space during
moderate exercise (Fig. 3) is consistent with previous studies that
showed a vigorous ventilatory response to added inspired
CO2 (8) and an increased
VT with added dead space (29,
33, 36) in normal subjects throughout exercise. However, our
observations of a significantly attenuated ventilatory response to
added dead space during heavy exercise (vs. moderate-intensity exercise) agree only with those studies in which endurance-trained runners were used as subjects (4, 17). Johnson and co-workers (17)
investigated the correspondence of significant expiratory flow
limitation with the reduced ventilatory response to added chemical
stimuli. They showed some increase in
E with added CO2 as long as there was room
under the MFVL for increases in flow rate but a greatly attenuated or
even no increase in
E in the
presence of significant expiratory flow limitation. Although Clark and
co-workers (4) did not measure expiratory flow limitation, they found
that the attenuated ventilatory response to added inspired CO2 in endurance-trained men only
occurred at a high ventilatory demand (>120 l/min), where in our
experience some degree of expiratory flow limitation would likely occur
in most subjects. We also note that some highly trained subjects have
been reported to have exceptionally large MFVL and, therefore, may not
experience expiratory flow limitation even at very high ventilatory
requirements (2).
E during heavy
exercise (Fig. 2). Notably, this decreasing relative contribution of
VT to increases in
E began at a
workload where no significant expiratory flow limitation was evident,
suggesting that flow limitation was not mandatory. However, despite the
lack of expiratory flow limitation when the decreasing contribution of
VT began, EILV had risen above
85% of TLC (Fig. 3B). It would appear, therefore, that, to prevent lung volumes from encroaching on
the stiffer portion of the lung and chest wall pressure-volume curves,
increasing breathing frequency may have been the best available option
for increasing
E.
Furthermore, as our subjects progressed from heavy to maximal exercise,
we observed a substantial rise in EELV (Fig.
3A), presumably caused by the onset
of significant expiratory flow limitation. With an EILV at 90% of TLC,
we also showed that VT actually
decreased at maximal exercise relative to heavy exercise (Fig.
4B). Again, this suggests a
mechanical constraint on VT, in
that further increases in EILV (>90% of TLC) do not appear to be an
available option. The effects of increasing flow limitation on
ventilation, breathing pattern, and lung volumes were also reflected in
a reduced gain of the ventilatory response to added dead space.
The use of HeO2 provided us with
an important tool to test experimentally the correlative evidence
obtained during exercise with air breathing and with added dead space,
as summarized above. We noted that
HeO2 breathing was without
significant effect on the ventilatory response to added dead space when
expiratory flow limitation was not present. However, when flow
limitation was eliminated by breathing
HeO2 during heavy and maximal
exercise intensities, hyperventilation ensued and the slopes of the
ventilatory response to added dead space increased and approximated the
response gains observed during moderate exercise. Increases in EELV and reductions in VT with
heavy-intensity exercise and with added dead space were also prevented
when expiratory flow limitation was eliminated via
HeO2.
We interpret these correlations between expiratory flow limitation and
reduced ventilatory response slopes, along with the observed effects of
HeO2 breathing, to mean that when
significant expiratory flow limitation is incurred during heavy
exercise, EELV will increase, EILV will rise to within 10% of TLC, and
increases in VT and
E will be
constrained. What began then as a resistive load on expiration resulted
in an increasing elastic load on inspiration. Indeed, the combination
of increased EELV (which reduces the capacity for pressure generation
by the inspiratory muscles) and the high volumes reached at EILV means
that pressure generation by the inspiratory muscles often reaches
80-90% of their dynamic capacity during maximal exercise in
highly trained individuals. These data suggest then that the regulation
of lung volume becomes a critical determinant of the breathing pattern
and the ventilatory response to heavy and maximal exercise in the
presence of expiratory flow limitation. Although we commonly refer to
the maximal VT achieved in
exercise as a fraction of VC for use as a reference standard in
comparing subjects (6, 8, 28), in view of the importance of a changing
EELV, it would be more appropriate to use
VT/IC as the regulated variable.
Additional mechanical constraints on the ventilatory response. We have attributed the constraint of the ventilatory response during heavy exercise and to increased dead space to expiratory flow limitation and its sequelae of effects on hyperinflation and increased elastic inspiratory loads (see above). However, there are other potential mechanical constraints that occur during heavy exercise that should be considered. First, as VT and breathing frequency increase and expiratory time shortens with increasing exercise intensity, expiration becomes active and causes reductions in EELV below resting FRC (6, 9, 13, 32). Accordingly, expiratory muscle work increases substantially in heavy exercise, and if fatigue in these expiratory muscles occurs, then this could conceivably explain at least some of the observed increase in EELV. Although this possibility has not been tested directly, it seems unlikely, especially during very-short-term heavy exercise, inasmuch as continued increases in gastric pressure have been observed as EELV increases with increasing exercise intensity (13, 35). Furthermore, the Pes achieved during expiration in heavy exercise at the time EELV has begun to increase are substantially below the peak levels of expiratory pressure that can be voluntarily achieved under these conditions (14, 24).
Second, given the very high inspiratory flow rates and velocity of muscle shortening achieved in heavy exercise (and with added dead space), a significant flow-resistive load on the inspiratory muscles must account for at least a portion of the mechanical constraint on the ventilatory responses. Two types of evidence speak against this mechanism being a major contributor. First, unloading of inspiratory and expiratory muscle work (by as much as 50-60%) with use of a proportional-assist ventilator has shown little systematic effect on the ventilatory response to heavy or maximal exercise, even in highly trained subjects withE >150 l/min (10, 25). We do need to add the important caveat for these
studies that a strong behavioral response to positive-pressure mechanical ventilation during exhaustive exercise may override any
potential reflex feedback effects emanating from respiratory muscle
unloading. Second, previous HeO2
breathing studies were conducted at high work rates in highly trained
women (28). Although all these subjects produced comparably high levels
of inspiratory flow rate and
E during
exercise, not all experienced significant expiratory flow limitation.
Among these women, the HeO2
influence on preventing the increase in EELV and enhancing
VT and
E (as presently shown) occurred only in those who experienced measurable expiratory flow limitation during air breathing.
In summary, we believe that these reports, along with present findings,
present a strong argument in favor of
1) a significant mechanical
constraint to increasing VT and
E
during heavy exercise commensurate with the onset of expiratory flow
limitation and 2) the postulate that
expiratory flow limitation leading to relative hyperinflation is the
dominant mechanical constraint to the
VT and ventilatory response to
heavy exercise.
Flow "limitation" and its compensatory responses are on a
continuum.
The increase in EELV and the constrained response of
E to added
dead space began to occur when there was still substantial room within
the maximal flow (and pressure)-volume envelope to increase expiratory
and inspiratory flow rate and pressure. In fact, during submaximal
heavy exercise intensities when the EELV began to increase and the
ventilatory response to added dead space was significantly reduced,
<40% of the VT intersected
the maximal flow-volume envelope. Furthermore, Ppl observed during
tidal expiration approximated normal values for maximal, effective
pressure during a brief fraction of expiration (17, 30). Also, on the
inspiratory side, we estimated that peak Ppl would be only 60-70%
of Pcap,i (Fig. 6). As exercise
intensity was increased to maximum, further increases in
E caused more
flow limitation, increased EELV, pushed inspiratory pressure closer to
Pcap,i, and caused greater reduction in and, in some cases, even flattened the slope of the E and Pes
responses to added dead space. However, even under these circumstances,
20-30% of the maximal flow-volume envelope remained unused.
E in response
to alterations in flow limitation with changes in perception of
breathing effort. However, given the wide variety of sensory inputs
associated with exhaustive exercise and added chemical stimuli, it is
perhaps not unexpected that subjects were unable to consciously
discriminate all superimposed reductions in flow limitation.
Summary and relevance.
The mechanical constraints to flow and volume have a significant
influence on the ventilatory response, lung volumes, and breathing
pattern during heavy exercise in those endurance-trained subjects who
experience expiratory flow limitation. Two types of findings support
this conclusion: 1) the reduction in
the ventilatory response and increase in EELV with added dead space as
tidal expiratory airflow intersected the MFVL in heavy exercise and
2) the prevention of these effects
on EELV, VT, and
E when
HeO2 breathing was used to
eliminate flow limitation. These data point to significant feedback
inhibition of respiratory motor output during heavy exercise, which
becomes evident under conditions of significant but not complete
expiratory flow limitation. These mechanical constraints on
E likely
explain, in part, why many highly trained subjects show relatively
little hyperventilation during heavy exercise (7, 11, 12, 17). The
result is that they fail to compensate for an excessively widened
alveolar-arterial PO2 difference; thus arterial hypoxemia occurs and systemic
O2 transport and
O2 max are limited.
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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. §1734 solely to indicate this fact.
Address for reprint requests and other correspondence: J. A. Dempsey, Dept. of Preventive Medicine, John Rankin Laboratory of Pulmonary Medicine, 504 N. Walnut St., Madison, WI 53706-2368.
Received 21 July 1998; accepted in final form 9 December 1998.
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REFERENCES |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
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) and during 6 incremental exercise workloads (52, 65, 74, 88, 95, and 100% of 
and 
, Flow rate response
to added dead space. B: group mean
tidal pressure-volume loops during moderate, near-maximal, and maximal
exercise during
N2O2
breathing. Solid lines,
N2O2
with no added dead space; dashed lines,
N2O2
with 1 liter of dead space. 
