endurance exercise; minute ventilation; respiratory muscle
pressure; postinspiratory inspiratory activity
 |
INTRODUCTION |
THE PATTERN OF RESPIRATORY muscle recruitment and the
individual contribution of the different respiratory muscle groups to ventilation at rest and during exercise have been the focus of many
studies. At rest, inspiration is predominantly a result of diaphragmatic contraction (19, 27), whereas expiration is a passive
process determined by the interaction of inspiratory muscle pressure
decay ("expiratory braking") and the elastic characteristics of
the respiratory system (2, 31, 37). It is well documented that, during
mild and moderate exercise, other inspiratory-accessory and expiratory
(abdominal) muscles are recruited to meet the increasing flow
requirements (19, 20, 27). Furthermore, it has been shown that, during
heavy endurance exercise [>80% maximal
O2 uptake (
O2 max)],
inspiratory-accessory muscles contribute more to the increase in
inspiratory airflow, whereas diaphragmatic pressures plateau (22, 29).
In a recent report, however, Aliverti et al. (6) showed that, although
transdiaphragmatic pressure increased only modestly, the dramatic
increases in the velocity of diaphragm shortening and diaphragmatic
work suggest that the diaphragm behaves essentially as a flow
generator, rather than as a pressure generator, at increasing exercise
intensities. The authors (6) also suggested that there is an immediate
increase in central drive to all respiratory muscle groups in the
transition between quiet breathing and exercise and that this drive
increases equally and proportionally to all muscle groups with
increasing exercise intensity thereafter. The translation of this drive
(into force or velocity of shortening), however, depends on the load on
the specific muscle groups. For example, the increase in abdominal
pressures during exercise serves to off-load the diaphragm, thus
enabling a dramatic increase in its velocity of shortening (flow), with
only a modest increase in its force (pressure).
Increasing expiratory muscle recruitment during exercise has been
inferred from the measurement of rib cage and abdominal volume
displacements (17, 19, 20) and changes in end-expiratory lung volume
(23, 28) and expiratory pleural (24, 26) and/or gastric pressures (11).
Recent studies in humans also indicate that although inspiratory
pleural pressures plateau, expiratory pleural pressures continue to
increase throughout heavy endurance exercise (24). More recently,
Sliwinski et al. (38) showed that, during heavy exercise after
induced global inspiratory muscle fatigue, increasing tonic and
phasic abdominal muscle pressures contribute to maintain tidal volume
(VT), despite reduced
diaphragmatic and rib cage inspiratory muscle activity. In addition to
increasing airflow, expiratory muscle activity during exercise reduces
end-expiratory lung volume (EELV) (20). The resultant increase in
elastic recoil combined with the relaxation of the abdominal muscles at
end expiration contributes significantly to lung inflation (19).
Furthermore, the persistence of abdominal muscle relaxation
well into inspiration has been interpreted as assisting in
diaphragmatic output, while stabilizing the rib cage, thus reducing
distortion (6).
During moderate prolonged exercise [e.g., <50% of maximal work
rate
(
max)],
minute ventilation
(E)
increases initially but stabilizes soon thereafter (24).
E,
however, continues to increase throughout constant-work heavy exercise
(CWHE, >70% max) (22, 24,
25), resulting in an ever-increasing load on all the respiratory
muscles. A variety of indexes, i.e., rib cage-abdominal pressure-volume
(P-V) relationships (17, 19, 20, 27), electromyography (EMG) (11), and
pressure (11, 17, 19, 20, 22, 24, 26, 27), have been used to assess patterns of respiratory muscle activity during exercise. Although these
indexes provide for qualitative assessment, quantitative measures of
net respiratory muscle pressure throughout the breathing cycle during
heavy exercise have been relatively scarce. The measurement of
respiratory muscle pressure (Pmus) throughout the respiratory cycle,
however, provides information on the relative contributions of all the
inspiratory (not just the diaphragm) and expiratory muscles to the
ventilatory output of heavy exercise. Pmus measurements throughout the
respiratory cycle also allow for the assessment of postinspiratory
inspiratory activity (PIIA), by which inspiratory Pmus
(Pmus, I) activity
"brakes" the start of expiration (2, 37). Data from animal
studies suggest that diaphragmatic PIIA remains the same or increases
during exercise (5) or with hypercapnic ventilatory stimulation (34,
39). This study was designed to address the following issues:
1) What is the relationship between the ventilatory output and net respiratory muscle pressure (Total Pmus)
throughout the breathing cycle in humans performing CWHE to exhaustion?
2) What is the relative contribution
of inspiratory and expiratory pressures to
E during CWHE
in humans? 3) What happens
to postinspiratory activity of the inspiratory muscles in humans during CWHE?
Previous studies that have examined the relationship between
E and pressure
[measured as mouth pressure (Pm) at 100 ms into inspiration
(Pm0.1) (21, 28) or esophageal
pressure (Pes) (40)] or their rates of change (40) during
exercise have produced conflicting results. It has been suggested that
the nonlinear relationship between
E and
Pm0.1 during exercise (21, 28) was
due to the nonlinear increase in respiratory impedance during exercise
(21). As discussed elsewhere (41), although
Pm0.1 is a useful noninvasive
index of inspiratory muscle output, its interpretation during exercise
is confounded by 1) the reduction in
EELV, 2) changes in the shape of the
Pmus, I waveform (16, 41),
and 3) the varying temporal
difference between the start of neural and mechanical inspirations
(16). Furthermore, occluded airway pressure measured at the start of
inspiration does not necessarily reflect the complex interactions
between inspiratory and expiratory forces throughout the breathing
cycle that ultimately contribute to airflow with each breath. We have
therefore examined the relationship between
E and Pmus
measured throughout the respiratory cycle (Total Pmus and its
components) in subjects performing CWHE.
Pmus, I at any time during
exercise can be expressed in terms of the dynamic capacity
(Pcap, I) of the
muscles to generate that pressure. Although the demand on all
the inspiratory muscles increases during heavy exercise
(
Pmus, I), the
capacity to generate that pressure decreases
(
Pcap, I)
with increases in lung volume (23, 26) and inspiratory flow rate (3,
23, 26). Pmus, I has
therefore been measured as a fraction of volume-matched, flow-corrected
Pcap, I as an index of inspiratory muscle load during CWHE.
| |
METHODS |
Subjects
Six healthy men (average age 25 yr) with no previous history of
cardiopulmonary or neuromuscular disorders were recruited and gave
informed consent in writing. On a preliminary visit to the laboratory,
each subject had a physical examination, an electrocardiogram (ECG),
and a pulmonary function assessment. Absolute lung volumes were
measured in a body box (Cardio-Pulmonary Instruments, Houston, TX). The
subjects were physically active and well motivated to perform
exhausting exercise; subjects 1, 3,
and 5 exercised regularly (e.g.,
cycling, swimming, and weight training 3-4 times/wk),
subjects 2 and
4 took part in recreational exercise
(e.g., cycling and tennis), and subject
6 exercised infrequently. They were specifically advised to avoid any strenuous physical activity on the day of the test
and to refrain from food and caffeinated drinks for 2 h before exercise testing.
Equipment
Exercise tests were performed on an electrically braked cycle ergometer
(model 18070, Godart). Subjects wore noseclips and breathed through a
mouthpiece. Inspiratory and expiratory flows ()
were measured separately using two pneumotachograph-transducer (Fleisch
no. 3 and Validyne MP45, ±2
cmH2O) assemblies on either side
of a two-way nonrebreathing valve (model K271, Vacumed). The response
of this system was linear over the range of flows measured, and the
resistance of the inspiratory and expiratory limbs of the breathing
circuit was <1.0
cmH2O · l
1 · s
at flow rates up to 6 l/s. The individual flow signals (inspiratory and
expiratory) were monitored on a breath-by-breath basis for zero drift
(18) and were integrated electronically (Gould) to provide biphasic
and volume (V) throughout exercise. The expiratory pneumotachograph was heated. Respired gases
(O2 and
CO2) were monitored by a mass
spectrometer calibrated with two standard gas mixtures of known
composition. ECG and heart rate (HR) were recorded continuously using
standard chest leads. Intrapleural pressure (Ppl) was measured with an
esophageal balloon-catheter system connected to a pressure transducer
by standard techniques (33). The balloon was carefully positioned in
the esophagus, where the best Ppl signal was obtained (most negative at
end expiration and with the least cardiogenic artifacts) (33), and its
position and gas volume were checked before and after exercise. An
occlusion test was performed before and after exercise, as described
elsewhere (9). Ppl and Pm were measured with Validyne MP45 transducers and calibrated against a water manometer at the start of each test. All
signals (, V, Ppl, Pm, ECG, HR,
O2, and
CO2) were recorded continuously
on an eight-channel strip-chart recorder (model 8000, Gould), sampled
(at 100 Hz), and digitized. Minute-by-minute exercise data were then
analyzed on a microcomputer.
Maximal Incremental Exercise
At least 3-5 days before CWHE, each subject performed an
incremental exercise test to volitional maximum. Exercise began at 50 W
after 2 min of breathing at rest. The workload was then raised incrementally (25 W/min) until the subject was unable to continue exercise. O2 max was
calculated from the minute of the last completed workload
(max).
Chest wall mechanics.
Static elastic recoil of the chest wall (Pw,el) and inspiratory
muscle strength
(Pmax, I)
were measured in all subjects on a separate occasion. Care was
taken to obtain the measurements in a position identical to
that assumed on the cycle ergometer during exercise. Two methods were
used to measure Pw,el (see below), and reproducible measurements
of Pw,el were available from at least one method in each subject. In
normal subjects, the results obtained by both techniques have been
shown to be equivalent (14).
Relaxation technique.
The subjects were trained to relax against an occluded airway after
full inspiration to total lung capacity (TLC), as described previously
(35). The occlusion was then released in a stepwise fashion, during
which the subject expired passively through a flow resistor. Relaxation
pressures (Ppl) were obtained during occlusion, at various lung volumes
below TLC. That the subject was relaxed was confirmed by observing the
Ppl signal for a steady plateau (without artifacts) that was
reproducible at each volume step. The maneuver was repeated several
times, and only the relaxed, reproducible data were used to construct
the chest wall P-V relationship (Fig. 1).
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Fig. 1.
Static chest wall recoil (Pw, el) and most negative inspiratory
pleural pressure (Pplmin) at
various lung volumes (vol) below total lung capacity (TLC) in 1 subject. Inspiratory muscle strength
(Pmax, I) was
measured as Pw, el  Pplmin at that lung volume.
Pmax, I was
further corrected to derive dynamic capacity of inspiratory muscles to
generate pressure
(Pcap, I) at a
given lung volume and flow rate.
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Weighted spirometry.
A modification of the weighted-spirometry technique (13, 14) was
employed. A special loading-unloading device (25) was used to apply
static positive airway pressures and was connected to a closed
breathing system that had a regulated 100%
O2 supply and a
CO2 absorber on the expiratory
limb. All the subjects were encouraged to breathe normally and relax
their respiratory muscles at end expiration. The subject was seated
comfortably and breathed on the apparatus for 3-5 min until the
inspired O2 concentration stabilized at 21% and EELV was stable. With the subject thus relaxed, static airway pressures (1-8
cmH2O) were applied at 2-min
intervals. The changes in the baseline EELV (
V) and Ppl at end
expiration (Ppl) were measured at each pressure step. That the
subject was relaxed was confirmed by the breath-by-breath
reproducibility (during several breaths) of the end-expiratory Ppl
values at each pressure step. The chest wall P-V relationship was then
constructed using Ppl measured at functional residual capacity and the
slope of the V-Ppl relationship.
Inspiratory muscle strength.
The subject was instructed to exert maximal inspiratory efforts against
an occluded airway at various lung volumes from TLC down to residual
volume. The most negative Ppl
(Pplmin) was measured during
these efforts. Ppl displayed on an oscilloscope served as visual
feedback to the subject to maximize his efforts. Lung volume at each
step was corrected for decompression and a
Pplmin-V curve was then
constructed in each subject (Fig. 1).
CWHE
While seated on the cycle ergometer, each subject was first trained to
make inspiratory capacity (IC) maneuvers. This was followed by 2 min of
quiet breathing and a short warm-up exercise (50 W for 2 min). The
subject was then alerted, and the workload was abruptly raised to the
predetermined level (~80%
max; Table 1). The subject used speedometer feedback
to pedal at 50-70 rpm against this workload until exhaustion. At
the end of every 2 min during CWHE, each subject was instructed to
inhale to TLC and hold his breath, with glottis open, for 1 s (IC
maneuver). The validity of these IC maneuvers (full inspiration to TLC)
was ensured by one investigator who monitored lung volume and Ppl (PplIC) throughout each exercise
test.
Data Analysis
For each minute of exercise, the computer counted and labeled all valid
breaths (except those interrupted by swallowing, cough, and after IC
maneuvers, <5-6/min). The onset and end of inspiratory and
expiratory were identified. The computer then
calculated inspiratory (TI),
expiratory (TE), and total
breath (TT) durations for each
breath. VT was obtained by
digital integration of expiratory flow to calculate
E.
The computer also derived (by interpolation) the average time course of
all signals (e.g., and Ppl) at 1% intervals of
TI and
TE. The time course of Pmus
(Fig. 2) throughout the respiratory cycle
was then calculated using previously described techniques (12, 16, 32,
42) for each minute of exercise
|
(1)
|
where
Pw, el and Pw, res are the pressures required to overcome
the elastic and resistive forces across the chest wall, respectively, and Ppl is pleural pressure. It should be emphasized that Pmus and its
components change throughout the respiratory cycle (Fig. 2).
Pw, el at each point in time was derived from instantaneous lung
volume and that subject's chest wall P-V curve. Pw, res was calculated from
|
(2)
|
where
is flow at that time (positive during inspiration
and negative during expiration) and Rw is chest wall resistance. A
value of 1.0 cmH2O · l1 · s
was used for Rw, inasmuch as this is the normal value of Rw for
subjects of this age, and there is very little variation between
results of different studies (7, 8). By this technique, inspiratory
pressures (Pmus, I) are
positive and expiratory pressures (Pmus, E) are negative
(Fig. 2).
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Fig. 2.
A: respiratory muscle pressure (Pmus)
throughout the breath during exercise in 1 subject. Inspiratory Pmus
(Pmus, I) is positive,
and expiratory Pmus
(Pmus, E) is negative.
Pcap, I at
matched lung volume and flow rate and at each point within the breath
during which Pmus is inspiratory (positive: +ve) is also shown.
Pmus, I during inspiratory
flow
(Pmus, IIF)
and postinspiratory inspiratory activity
(Pmus, IPI,
shaded region) are clearly demarcated.
B: time course of
Pmus, I/Pcap, I
(%) ratio during the breath. All mean values are averaged over total
respiratory cycle (see Data
Analysis).
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The method used to calculate
Pmus, I and
Pmus, E for each minute of
CWHE is illustrated in Fig. 2. Mean
Pmus, I was calculated as
the area of the positive segment of the Pmus waveform averaged over
TT
|
(3)
|
Pmus, I throughout
each breath was subdivided into its component parts:
Pmus, I during mechanical
inspiration (during inspiratory flow,
Pmus, IIF)
and Pmus, I persisting
during the initial part of expiration (PIIA,
Pmus, IPI;
Fig. 2, shaded area). Mean
Pmus, IIF
was then calculated as
|
(4)
|
and
mean
Pmus, IPI
was calculated as
|
(5)
|
and
mean Pmus, E (negative
Pmus) was similarly averaged over
TT
|
(6)
|
The net pressure generated by all the respiratory muscles,
averaged over the respiratory cycle (Total Pmus) is the "sum" of
average inspiratory and expiratory (absolute value) muscle pressures
|
(7)
|
Pmus, I at each
point in time was expressed as a fraction of that subject's capacity
(Pcap, I) to
generate Pmus, I at the
same lung volume and flow rate. First, to calculate Pmax, I
corrected for lung volume, the measured Pw, el and
Pplmin data for each subject were
analyzed graphically. Only maximal inspiratory efforts were taken into
account, and a second-order polynomial was used to fit the outer
envelope of the Pplmin-V
relationship (Fig. 1). All submaximal efforts therefore lay within this
curve, and these measurements were discarded. In each subject, static
volume-matched
Pmax, I on a
breath-by-breath basis was then derived digitally, as the horizontal distance between the Pw, el and
Pplmin curves at each lung volume increment, at all points when Pmus was inspiratory (positive Pmus; Fig.
2)
|
(8)
|
The force-generating capacity of the inspiratory muscles
declines with increasing velocities of muscle shortening (3), and this
has been shown to correlate with increases in flow rates (36). It has
been shown that, at any given lung volume,
Pmax, I falls by
~5% for every 1 l/s increase in flow rate (23, 26). Each subject's
capacity
(Pcap, I) to
generate Pmus I at any
lung volume and for a given flow rate was therefore calculated as
|
(9)
|
Figure 2A shows
Pcap, I
throughout inspiration in one subject. As shown in Fig.
2B,
Pmus, I was then
represented as a fraction (%) of
Pcap, I at the
same lung volume and flow rate, at each point in time during which Pmus
was positive, for each breath. Like the other Pmus variables, mean
Pmus, I/Pcap, I (%) values were averaged over
TT
|
(10)
|
For all the ventilatory and Pmus variables, statistical
comparisons between the 3rd min of CWHE and end-exercise values were made using a paired t-test, and
P < 0.05 was accepted as
significant. The relationships between
E and Pmus
variables were examined graphically and analyzed with regression
analyses. A straight-line and a second-order polynomial function were
used to fit each of the data sets in each subject to determine whether
any of the E-Pmus
relationships were linear or curvilinear. A
t-test (ANOVA) was then used to
determine whether the 
-coefficients of the quadratic equation
provided a significantly better fit than a linear equation. Data are
presented as means ± SE unless indicated otherwise.
| |
RESULTS |
The subjects were moderately fit (108 ± 5% predicted
O2 max) and completed
all exercise tests to exhaustion. In the CWHE test the subjects
exercised for 14 min on average at a mean work rate of 260 W (81 ± 2% max).
Although dyspnea at end exercise was described as "moderate" or
"heavy," exercise cessation was attributed to leg fatigue by each
subject. Table 1 summarizes subject characteristics and exercise
performance data.
Table 2 summarizes the average changes
(%) in metabolic rate, HR, and other ventilatory variables from 3 min to the end of CWHE. Consistent with data from previous studies of
CWHE (22, 24, 25),
E and HR
increased significantly throughout exercise. End-exercise
O2 uptake, HR, and
E values were
similar to those at the end of maximal incremental exercise (Table 2).
The temporal courses of
E, end-tidal
PCO2
(PETCO2), and lung volumes
during CWHE are illustrated in Fig. 3.
E (Fig.
3A) increased rapidly at the start of exercise and continued to
increase throughout CWHE. All the increase in
E ( = 60 ± 9%, P < 0.005) from 3 min to
end exercise was due to a significant increase in breathing frequency
( = 64 ± 6%, P < 0.005).
After an initial increase at the start of exercise, VT did not increase further
during CWHE; VT decreased
slightly with increasing exercise time in three subjects, similar to
previous reports (24), but this fall from 3 min to the end of CWHE
(VT; Table 2) was not
statistically significant. The E
drift of CWHE was associated with a progressive fall in
PETCO2 (Fig. 3B),
which was significant: from 40.0 ± 0.8 Torr at 3 min to 29.2 ± 1.0 Torr at end exercise (P < 0.005).
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Fig. 3.
Minute ventilation
(E;
A), end-tidal PCO2
(PETCO2; B),
and lung volume (%TLC; C) during exercise.
EILV and EELV, end- inspiratory and end-expiratory lung volume;
VT, tidal volume. Values are
group means ± SE (n = 6) at 10%
increments of exercise time.
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Figure 3 also describes the average time course of the limits
of exercise VT throughout CWHE.
End-expiratory lung volume was derived from measured IC (EELV = TLC IC). TLC was assumed to be constant during CWHE, for it has
been shown that TLC remains unchanged during incremental and endurance
exercise in normal subjects (30, 42). The IC measurements were
validated by the reproducibility of Ppl values at the end of a full
inspiration (PplIC).
PplIC did not change significantly
during CWHE: 38 ± 4 cmH2O at rest, 40 ± 5 cmH2O at 50% exercise duration,
and 37 ± 4 cmH2O at end
exercise. End-inspiratory lung volume (EILV) was derived as the sum of
VT and EELV. As Fig. 3C
illustrates, most of the changes in the limits of exercise
VT occurred at the start of
heavy exercise; after the first 3 min, EELV and EILV remained
essentially stable throughout CWHE. EELV decreased significantly at the
start of exercise: from 3.52 ± 0.26 liters (53 ± 2% TLC) at
rest to 3.01 ± 0.27 liters (45 ± 3% TLC) at 3 min
(P < 0.05). EILV increased
significantly at the start of exercise, from 4.38 ± 0.36 liters (65 ± 3% TLC) at rest to 5.62 ± 0.26 liters (84 ± 2% TLC) at
3 min (P < 0.05), but did not change
significantly thereafter.
Table 3 summarizes the changes in
respiratory mechanics from 3 min to the end of exercise. With the
significant (and equal) increases in inspiratory (mean
I = 1.77 ± 0.31 l/s, P < 0.005) and expiratory
(mean
E = 1.80 ± 0.37 l/s, P < 0.005)
flows during CWHE, Ppl (peak and mean values) during inspiration
increased significantly. However, there was a greater increase in peak
expiratory Ppl (Ppl, E),
and this increase in
Ppl, E (>4 times) was
significant (P < 0.005). Inspiratory
and expiratory lung resistances
(RL, I
and
RL, E,
respectively) at 1.0 liter above EELV were calculated using the
subtraction technique of Mead and Whittenberger (32). RL, I
and
RL, E
increased from 3 min to the end of CWHE, and as shown in earlier
studies (16),
RL, E
was greater than
RL, I in five of six subjects during CWHE. The increase in
RL, E
from 3 min to the end of CWHE was significant
(P = 0.048). However, this greater
increase in
RL, E
could not be attributed to a greater increase in mean expiratory flow,
because, as shown in Table 2, TI/TT
remained unchanged (at 0.5) from 3 min until the end of CWHE. Table 3
also shows that dynamic lung compliance increased slightly from 3 min
to the end of CWHE in five of six subjects. However, these changes were
small (24%) and not statistically significant.
Pmus data at 3 min and at end exercise are summarized in Table
4. Figure 4
illustrates the Pmus waveforms at 3 min and at end exercise in each
subject. Pmus, I is
positive, and Pmus, E is
negative. Four of six subjects showed an increase in peak and mean
Pmus, I from 3 min to end
exercise; however, subjects 2 and 6 showed little or no change in peak
Pmus, I and a slight fall in mean Pmus, I from 3 min
to end exercise. These two subjects (2 and 6, Fig. 4) displayed substantial
Pmus, IPI
at 3 min (23 and 17% of Total
Pmus, I, respectively),
but not at the end of CWHE. Although
Pmus, IPI
fell significantly from 14% of net
Pmus, I at 3 min to 4% of
net Pmus, I at end
exercise (Table 4),
Pmus, IIF
increased significantly from 11.2 ± 1.1 cmH2O at 3 min to 15.2 ± 1.8 cmH2O at end exercise (Table 4).
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Fig. 4.
Pmus at 3 min (A) and at end
exercise (B) in each subject
(identified by numbers at left).
Pmus, I is positive, and
Pmus, E is negative.
Shaded segment of Pmus, I
waveform is
Pmus, IPI.
Mean Pmus, I and mean
Pmus, E are averaged over
respiratory cycle. Values in parentheses represent fractional
contribution of
Pmus, IPI
to Total Pmus, I.
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Figure 4 also shows the changes in
Pmus, I waveform with the
increasing levels during exercise. The shape of
Pmus, I changed significantly; i.e., the
Pmus, I waveform became
increasingly concave toward the time axis. The ratio (%) of
Pmus, I at 50% of the
rising duration of positive Pmus to peak
Pmus, I was calculated as
an index of the shape of
Pmus, I. This index
increased significantly (P < 0.01)
from 62 ± 3% at 3 min to 74 ± 3% at end exercise. Although there was some variation in the increase in
Pmus, I among subjects, Fig. 4 shows that peak and mean expiratory pressures
(Pmus, E) increased
consistently from 3 min to end exercise in all subjects. Mean
Pmus, E increased
significantly from 3.0 ± 0.5 cmH2O at 3 min to 6.9 ± 0.5 cmH2O at end exercise ( = 168 ± 48%, P < 0.005; Table 4).
This increase in Pmus, E
resulted in a doubling of the mean
Pmus, E-to-mean
Pmus, I ratio from 3 min
(23%) to end exercise (46%).
We wished to determine whether the greater increase in expiratory
muscle pressures in these subjects was "excess pressure" resulting from expiratory flow limitation during CWHE. As maximal -V measurements were not included in the study
protocol, tidal -V data from the last minutes of
exercise were analyzed in each subject. Data from 3 min and 1 min
before end exercise and at end exercise revealed that inspiratory and
expiratory flows continued to increase until end exercise. That these
subjects increased their expiratory flow rates at the same lung volume
suggests that expiratory flow limitation did not occur, on the average.
This is also supported by the observation that EELV did not change over
the last 3 min of CWHE (Fig. 3). Because it was still possible that
individual subjects might have had flow limitation,
-V data in each subject were examined. Five of six
subjects continued to increase expiratory flow rates over the last few
minutes of exercise, but one subject did not do so over the last minute
of exercise. Therefore, expiratory flow limitation may have been present in this one subject but was unlikely in the other five subjects.
Figure 5 illustrates the average
(n = 6) Pmus data at 3 min and at end
exercise. Pmus, I is
positive, and Pmus, E is
negative. As in Fig. 4, group mean
Pmus, I, mean
Pmus, E, and
Pmus, IPI (%Pmus, I) are given.
Peak and mean Pmus, I
increased from 3 min to end exercise, but these increases (>20%)
failed to reach statistical significance
(P = 0.07).
Pmus, E increased
significantly from 3 min to end exercise; in relative terms, this
increase (168 ± 48%) was significantly greater than that observed
with mean Pmus, I.
However, as Table 4 reveals, the increase in
Pmus, E in absolute terms
(~4 cmH2O) is identical to the
increase in
Pmus, IIF.
The increase in mean
Pmus, I from 3 min to the
end of CWHE was smaller as a result of the significant fall in
Pmus, IPI
during CWHE (also see below).
Pmus, IPI
fell significantly from 3 min to the end of CWHE.
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Fig. 5.
Group mean Pmus and
Pmus, I/Pcap, I
(%) at 3 min (A and C) and
at end exercise (B and D).
Pmus, I is positive, and
Pmus, E is negative.
Shaded region of Pmus waveform is
Pmus, IPI.
Fractional contribution of
Pmus, IPI
to Total Pmus, I is
indicated. Mean values are averaged over respiratory cycle.
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As outlined in METHODS,
Pmus, I was expressed as a
fraction of Pmus during a maximal inspiratory maneuver
(Pcap, I) at the
same lung volume and flow rate. Average
Pmus, I/Pcap, I (%) throughout inspiration at 3 min and at end exercise is also shown
in Fig. 5. The subjects generated a wide range of
Pmus, I/Pcap, I
values: peak
Pmus, I/Pcap, I ranged from 25 to 80% and increased from 3 min (50 ± 5%) to end exercise (71 ± 11%). This increase, however ( = 44 ± 18%;
Table 4), failed to reach statistical significance
(P = 0.055). Mean Pmus, I/Pcap, I
averaged over the respiratory cycle is the tension-time
index1
of the inspiratory muscles. This index increased significantly from
17.8 ± 2.0% at 3 min to 25.4 ± 4.3% at end exercise
(P < 0.05; Table 4). Figure 5 also
highlights the dynamic variations in the shape and intensity of the
Pmus and
Pmus, I/Pcap, I waveforms throughout the respiratory cycle.
The decrease in PIIA with increasing
E throughout
CWHE is summarized in Fig. 6. Group mean
duration of PIIA
(TPmus, IPI) at matched levels during CWHE is shown as a fraction of
TE and TT.
TPmus, IPI
fell progressively with increasing levels throughout CWHE; the values
at end exercise were less than one-half of those at the start of
exercise.
TPmus, IPI
decreased significantly (P < 0.05;
Table 4) from 3 min (33.5 ± 4.4%
TE and 16.9 ± 2.6%
TT) to end exercise (15.3 ± 0.8% TE and 7.6 ± 0.4% TT). Although the postinspiratory activity of the inspiratory muscles was significant throughout CWHE, postexpiratory activity of the expiratory muscles [Pmus, E persisting
during the period of inspiratory flow
(TPmus, EPE)]
was negligible in these subjects (1.3 ± 0.8 and 0.2 ± 0.2% TI at 3 min and end exercise,
respectively). Postexpiratory
Pmus, E activity similarly
was negligible (0.6 ± 0.5 and 0.03 ± 0.03% mean
Pmus, E at 3 min and end
exercise, respectively).
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Fig. 6.
Relationship between minute ventilation and postinspiratory inspiratory
activity during heavy exercise. Duration of postinspiratory inspiratory
activity
(TPmus, IPI)
is shown as fraction of expiratory
(TE) and total breath
(TT) duration. Note
progressive decline in postinspiratory inspiratory activity with
increasing ventilatory levels during heavy exercise. Values are group
means ± SE.
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The results of regression analyses between
E and various
Pmus variables during CWHE are presented in Figs.
7 and 8.
Figure 7 illustrates mean
Pmus, I-E
and mean
Pmus, E-E
relationships in each subject. Except in subject
4, it is evident that mean Pmus, I and mean
Pmus, E increase in a
linear fashion with increasing E during CWHE.
However, the correlation coefficient for a linear regression of mean
Pmus, I and mean
Pmus, E with
E in
subject 4 was significantly high
(r = 0.91, P < 0.05, in both cases). Although mean Pmus, I and
mean Pmus, E increased
linearly with increasing
E throughout
CWHE, there was considerable variation in the slopes (range
0.065-0.135
cmH2O · l1 · min)
and correlation coefficients (range 0.50-0.97) of the mean
E-Pmus, I
relationship. However, the
E-Pmus, E
relationship during CWHE in these subjects was more consistent, with
less variable slopes (range 0.051-0.083
cmH2O · l1 · min)
and correlation coefficients (range 0.82-0.93).
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Fig. 7.
Relationship between minute ventilation and mean
Pmus, I
(A) and minute ventilation and mean
Pmus, E
(B) in each subject (identified by
numbers at top left) during heavy exercise. Relationship
between minute ventilation and mean
Pmus, I and mean
Pmus, E is linear, except
in subject 4.
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Fig. 8.
Relationships between minute ventilation and Total Pmus (mean
Pmus, I mean
Pmus, E,
A) and minute ventilation and
inspiratory muscle tension-time index [mean
Pmus, I/Pcap, I
(%), B] during constant-work
heavy exercise. Group mean (n = 6)
data (averaged at 10% increments of exercise duration) show a
significantly linear relationship between minute ventilation and Total
Pmus (r = 0.99, P < 0.0001) and minute ventilation
and mean
Pmus, I/Pcap, I
(r = 0.99, P < 0.0025) during heavy exercise.
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In contrast to the variability observed in the
E-mean
Pmus, I and
E-mean
Pmus, E relationships, the
relationship between the net respiratory muscle pressure throughout the
breathing cycle (Total Pmus) and
E was highly
linear. In each subject, the
E-Total Pmus
correlation coefficient was significantly greater than the individual's
E-Pmus, I
or
E-Pmus, E
correlation coefficient. The slopes of this relation averaged 0.136 ± 0.020 cmH2O · l1 · min
(P < 0.0001, range
0.081-0.219). Only in subject 6,
however, was this relationship improved slightly with nonlinear
regression (r = 0.92 and
r = 0.90 with 2nd-order and linear
regressions, respectively). Total Pmus increased significantly
(P < 0.005) from 3 min to end
exercise ( = 43 ± 9%; Table 4). Figure
8A summarizes the group mean
E-Total Pmus
relationship (average of data at 10% increments of exercise duration)
during CWHE in these subjects.
Figure 8B also illustrates the
relationship between the inspiratory muscle tension-time index
[mean
Pmus, I/Pcap, I (%)] and
E and reveals
that the
E-mean
Pmus, I/Pcap, I relationship (shown as group mean data) was also linear during CWHE.
Subjects generated a wide range (6.2-35.8%) of mean
Pmus, I/Pcap, I
values during exercise, and, as Fig. 8 illustrates, mean
Pmus, I/Pcap, I
was >15% for all values >75 l/min. Furthermore, the
E-mean
Pmus, I/Pcap, I relationship in each subject was also significantly linear (average slope 0.162 ± 0.020% · l · min1,
P < 0.0025). In
subject 4 the correlation coefficients
for the second-order and linear regresssions were 0.98 and 0.97, respectively. For the
E-Total Pmus
and E-mean
Pmus, I/Pcap, I relations, the y-axis intercept was
not significantly different from zero.
The regressions between the slopes and intercepts of the
E-Total Pmus
and E-mean
Pmus, I/Pcap, I
(%) relationships (dependent variables) and respiratory system
resistance (Rrs) and elastance (independent variables) during CWHE were
tested. Although there were significant correlations between Rrs and
the slopes of the
E-Total
Pmus (r = 0.89, P = 0.016) and
E-mean Pmus, I/Pcap, I
(r = 0.82, P = 0.046) relationships in these
subjects, there were no significant relationships between Rrs and any of the intercepts. Furthermore, no significant
relationships were observed between respiratory system elastance and
the slopes and intercepts of the
E-Total Pmus
and E-mean
Pmus, I/Pcap, I relationships in these subjects during CWHE.
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DISCUSION |
The results of this study designed to examine the relationship between
ventilatory output and net Pmus during CWHE in humans showed that
1) inspiratory and expiratory muscle
pressures increased to meet the increasing ventilatory demands of CWHE,
2) the relationship between the
ventilatory output and the net pressure output of respiratory muscles
(Total Pmus and its components) is significantly linear during CWHE,
3) the ventilatory increase in CWHE
is associated with a greater increase in expiratory than inspiratory
muscle pressures, and 4) postinspiratory
(expiratory) activity of the inspiratory muscles in humans diminishes
significantly with the increasing ventilatory demands of CWHE.
Critique of Methods
The validity of our assessment of changes in net Pmus during heavy
exercise depends on the accuracy with which the components of Pmus
(Eq. 1) are measured. Pes, an
excellent index of changes in Ppl (33), has been used in many studies
(11, 17, 19, 24, 26, 40) and was validated before and after exercise in
this study by the occlusion technique (9). In contrast to our previous
work (16), Pw, el was measured in each subject by two established
techniques after adequate training (see
METHODS). Although the static
Pw, el-V relationship is linear within the range of volume limits
(35) observed in our study (EELV > 40% TLV and EILV < 90% TLC),
it does not account for dynamic pressure losses due to chest wall
distortion, a complex phenomenon when the dynamic P-V characteristics
of chest wall (and its geometry) deviate significantly from its
relaxation configuration (17, 19) as a result of increasing accessory
rib cage and abdominal muscle activity during exercise. Distortive
forces, although present in various degrees throughout the respiratory
cycle, are most marked at VT
extremes (17) (corresponding to peak pressures). Because the limits of
VT (EELV and EILV) changed very
little from 3 min to end exercise, it is probable that the pressure
losses due to distortion, although not measured under these conditions, were similar; i.e., changes in pressure () due to chest wall distortion would have been small compared with the changes in Total Pmus.
Rw, although dependent on VT and
breathing frequency in the normal range of breathing (8), tends to fall
with increased frequency (0.5-2 Hz), with most of the changes ( ~ 40%) occurring at the transition from 0.5 to 1 Hz (8).
The change in Rw from 3 min (frequency = 34 breaths/min) to end
exercise (frequency = 55 breaths/min) would therefore have been ~0.4
cmH2O · l1 · s,
resulting in Pw, res (Eq. 1)
being overestimated by <1 cmH2O and, in turn, mean Pmus, I
and mean Pmus, E being
overestimated by ~6 and ~16%, respectively, at end exercise. Pmus
(Eq. 1) is therefore a valid index
of respiratory muscle output during exercise in this study.
Pmus, I was further
expressed as a fraction (%) of the volume-matched, flow-corrected
Pcap, I, and this
Pmus, I/Pcap, I
(%) averaged over the respiratory cycle was used as the inspiratory
muscle tension-time index (10).
Respiratory Muscle Output During Heavy Exercise
Different techniques have been used to assess the specific
contributions of the different respiratory muscle groups to the exercise ventilatory response. Measurement of thoracoabdominal P-V
relationships (17, 19, 20, 27) reveal that although the diaphragm is
the main muscle of inspiration at rest, significant recruitment of the
inspiratory-accessory (rib cage) and the abdominal expiratory muscles
contributes to the increase during exercise. However, the pattern and
the magnitude of respiratory muscle activity have been shown to depend
on posture and the mode of exercise (cycle ergometry vs. treadmill
running) (20). Measurements of Pm (21, 28), Pes (24, 26),
transdiaphragmatic pressure (11, 22, 27), and gastric pressure (11, 20,
26) also provide clear evidence of increasing inspiratory and
expiratory muscle activity during exercise. Although Ppl has been used
commonly as an index of net Pmus, Eq. 1 shows that Ppl measurement by itself would
underestimate respiratory muscle output, inasmuch as it does not
account for static (Pw, el) and dynamic (Pw, res) pressure losses across the chest wall. Despite these limitations, Ppl
measurement during exercise serves as a good qualitative index of
respiratory muscle output. During incremental exercise, Leblanc et al.
(26) showed progressive increases in peak inspiratory and expiratory Ppl that indicate progressive increases in inspiratory and expiratory muscle pressures. In subjects performing CWHE at 80%
O2 max, Bye et al. (11)
reported a significant increase in expiratory abdominal pressure and
Ppl. More recently, Kearon et al. (24) showed that, with increasing
exercise time during CWHE at >80% max, although
inspiratory pressures tended to plateau, there was a progressive
increase in peak and end-expiratory Ppl. Johnson et al. (22) also
reported a significant increase in the time integral of Pes throughout
exercise with the increases in
E and
inspiratory flow during heavy exercise (>85%
O2 max). In contrast,
the time integral of transdiaphragmatic pressure was shown to plateau
early in exercise in their study, suggesting that the diaphragm was
contributing less and the "inspiratory-accessory" muscles more to
the hyperventilatory response to heavy exercise. However, these
pressure measurements do not directly reflect the recruitment patterns
of the diaphragm or intercostal muscle groups, inasmuch as their
relative shortening and velocities of shortening are not accounted for
(6). Other evidence also confirms increased inspiratory/intercostal
muscle and/or reduced diaphragmatic pressures (27) during exercise; for
example, Johnson et al. showed that post-exercise diaphragmatic
fatigue was less in the subjects in whom diaphragmatic pressure was
decreased or minimal for most of heavy exercise. Similar findings have
been reported in subjects performing cycle ergometer CWHE (at 80%
max) to
exhaustion (29).
The significant and proportional increase in abdominal expiratory
muscle EMG in humans during CO2
inhalation and its persistence in early inspiration (1) indicate that
these muscles contribute to inspiratory flow under augmented
ventilatory conditions. EMG data from specific inspiratory and/or
expiratory muscles in animals also indicate increased respiratory
muscle recruitment whenever E is increased
as a result of chemical stimulation (39) or during exercise (4, 5). All
the above evidence suggests that increasing inspiratory-accessory and
expiratory muscle activity contribute significantly to the ventilatory
response to exercise.
The technique of quantitative assessment of respiratory muscle activity
throughout the breathing cycle during exercise in humans in this study
is based on that of Younes and Kivinen (42). Mean
Pmus, I,
Pmus, E, and
E (14.0 cmH2O, 3.0 cmH2O, and 80.7 l/min,
respectively) at the end of maximal incremental exercise in their study
were very similar to those at 3 min in our study (Tables 2 and 4).
Consistent with previous studies (see above), our results also showed
significant inspiratory and less significant expiratory muscle
pressures in early exercise (3 min; Fig. 5). However, the subsequent
temporal courses of
Pmus, I and
Pmus, E during CWHE were
quite different. Although mean
Pmus, IIF
increased significantly (and equally as mean
Pmus, E; Table 4) from 3 min to end exercise,
Pmus, IPI
decreased throughout CWHE. In relative terms, therefore, our subjects
showed a greater increase in
Pmus, E than in
Pmus, I from early to end
exercise. Although the increase in
Pmus, E and the reduction
in
Pmus, IPI
served to augment expiratory flow, increasing expiratory muscle
activity served to possibly determine (and maintain) optimal EELV
during exercise, thus helping the diaphragm and the other inspiratory
muscles operate on a more efficient range of their length-tension
relationships as well as allowing for a greater
VT in the linear P-V range of
the respiratory system (19, 20, 27). We interpret this progressive and
significant increase in
Pmus, E as "sparing"
the inspiratory muscles, for the expiratory muscles take on a greater
proportion of Pmus (from 19% at 3 min to 30% Total Pmus at end
exercise) with increasing E. Other
recent findings (38) have also shown that, during exercise after
induced global inspiratory muscle fatigue, progressively increasing
expiratory muscle activity significantly helps maintain the pressure
generation capacity of the diaphragm and rib cage inspiratory muscles.
Studies that have examined inspiratory muscle function (inspiratory Ppl
or diaphragmatic pressure) during incremental (26) or endurance
exercise (24) have shown that with increasing exercise intensity,
although the demand on the inspiratory muscles increases significantly, their
Pcap, I
decreases progressively. As
Pcap, I
varies with muscle length (lung volume) and velocity of shortening
(flow rates),
Pmus, I/Pcap, I (%) was calculated as a volume-matched, flow-corrected index of inspiratory muscle contraction throughout the breath in this study. As
Fig. 5 showed,
Pmus, I/Pcap, I
varied throughout the breathing cycle. Tension-time indexes, which
relate the force and duration of muscle contraction, have long been
used to assess endurance of the respiratory muscles; a critical
fatiguing value of 0.26 for the rib cage muscles (43) and 0.15 for the
diaphragm (10) have been suggested. Mean
Pmus, I/Pcap, I, the tension-time index of all the inspiratory muscles, was variable between subjects (Fig. 8) and averaged 17.8% at 3 min and 25.4% at
end exercise. This does not by itself imply that the inspiratory muscles were fatiguing during heavy exercise, inasmuch as it is very
unlikely that there is an invariant index above which fatigue always
occurs. Recent studies, however, reveal that the pressure-generating capacity of the diaphragm (22, 29) and expiratory muscle endurance (15)
are significantly compromised after exercise to exhaustion. Although
these studies suggest that respiratory muscle fatigue may be present
during heavy exercise, there is good evidence that it does not limit
exercise tolerance in humans (25, 38).
Relationship Between Ventilatory and Respiratory Muscle Outputs
During Exercise
Previous studies (21, 28) of the relationship between ventilation
(mechanical output) and indexes of respiratory neural output (drive) in
humans, by use of Pm0.1, suggested
that the faster increase in Pm0.1
(than of E)
was due to a nonlinear increase in the "effective impedance" of
the respiratory system during exercise (21). As discussed in detail
elsewhere (41), Pm0.1 measurements
during exercise may not accurately reflect inspiratory drive and/or
respiratory muscle output because of 1) the increased elastic
recoil due to reduction in EELV below functional residual capacity,
2) the changes in the shape of
Pmus, I (Figs. 4 and 5)
during exercise (16, 41), and 3) the
variability of the time difference between the onset of neural
inspiration and Pm0.1 measurement
(16). The nonlinear relationship between E and
Pm0.1, therefore, may not
necessarily reflect a true nonlinear increase in respiratory impedance
during exercise.
The linear relationship between
E and Pmus in
humans during heavy exercise shown in this study suggests that, in
addition to an efficient partition of work between inspiratory and
expiratory muscle groups, increases in net respiratory muscle pressure
throughout the breathing cycle (Total Pmus) and its components (mean
Pmus, I and
Pmus, E) are precisely
tuned to the ventilatory need of the exercising individual. Limited
data from animals performing exercise also suggest that the electrical
(EMG) and mechanical (pressure) activity of inspiratory and expiratory
muscles increase proportionately with exercise hyperpnea (4, 5). The
higher E-Total
Pmus correlation (compared with
E-mean
Pmus, I or E-mean
Pmus, E relationships;
Fig. 7) in each subject suggests that the net pressure generated by all
the respiratory muscles (not inspiratory or expiratory alone)
throughout each breath is determined by the ventilatory need of the
individual during heavy exercise. Furthermore, the linear relationship
between E and mean
Pmus, I/Pcap, I
(%) in all these subjects indicates that the dynamic load on the
inspiratory muscle load increases in direct proportion to the
ventilatory need of heavy exercise. The significant positive
correlations between Rrs and the slopes of
E-Total
Pmus and
E-mean
Pmus, I/Pcap, I
relationships in these subjects are consistent with the idea that
flow-resistive pressure losses are an increasingly important component
of Pmus as E
increases significantly throughout heavy exercise. However, as EILV and
EELV remain relatively constant throughout CWHE (Fig. 3), the elastic
load on the respiratory muscles changes very little with increasing
E.
Postinspiratory (Expiratory) Activity of the Inspiratory Muscles
During Exercise
This study also provides new evidence on the persistence of inspiratory
muscle activity in the first part of expiration (PIIA, Pmus, IPI)
in humans performing heavy exercise. Resting breathing in humans is
predominantly an inspiratory event from a respiratory muscle point of
view, and expiration is a result of passive relaxation and slowly
decaying Pmus, I, which
persists during and "brakes" expiration (2, 37). With the
substantial increase in breathing frequency during CWHE, the magnitude
and the rate of rise of
Pmus, I are increased
significantly, and the increased rate of decay of
Pmus, I from maximal
values (Figs. 4 and 5) has been shown to depend on breathing frequency
in humans (2).
Pmus, IPI
persists at the high
E levels
throughout exercise, however, during a smaller fraction of
TE. As Fig. 6 and Table 4 show,
the duration of PIIA and its magnitude at end exercise are ~50% of
the values at the start of exercise. Animal studies that have examined
PIIA, however, have shown that the the duration and the magnitude of changes in PIIA depend on the nature of the ventilatory stimulus. In
exercising dogs, for example, the duration of PIIA remains the same,
whereas there is progressive shortening of
TE, resulting in a relative
increase in PIIA (5). Hypoxia and hypercapnia have been shown to reduce
PIIA in some studies (34) but increase PIIA in others (39). The
combination of increased expiratory pressures wi
TOP
ABSTRACT
INTRODUCTION
