Expiratory
muscle fatigue in normal subjects
SHUNSUKE SUZUKI, JUNNICHI SUZUKI, AND TAKAO OKUBO First Department of Internal Medicine, Yokohama City University School of Medicine, Yokohama 232, Japan
SUZUKI,
SHUNSUKE,
JUNNICHI
SUZUKI,
AND
TAKAO
OKUBO.
Expiratory muscle fatigue in normal subjects. J. Appl. Physiol. 70(6): 2632-2639, 1991.-We examined expiratory muscle fatigue during expiratory resistive loading in 11 normal subjects. Subjects breathed against expiratory resistances at their own breathing frequency and tidal volume until exhaustion or for 60 min. Respiratory muscle strength was assessed from both the maximum static expiratory and inspiratory mouth pressures (PE mEu and PI,,). At the lowest resistance, PE,, and PI,, measured after completion of the expiratory loaded breathing were not different from control values. With higher resistance, both PE,, and PI,, were decreased (P < 0.05), and the decrease lasted for 260 min. The electromyogram high-to-low frequency power ratio for the rectus abdominis muscle decreased progressively during loading (P < O.Ol), but the integrated EMG activity did not change during recovery. Transdiaphragmatic pressure during loading was increased 3.6-fold compared with control (P < 0.05). These findings suggest that expiratory resistive loaded breathing induces muscle fatigue in both expiratory and inspiratory muscles, Fatigue of the expiratory muscles can be attributed directly to the high work load and that of the inspiratory muscles may be related to increased work due to shortened inspiratory time. resistive dominal
loaded breathing; muscles
maximum
expiratory
pressure;
ab-
OBSTRUCTIVE PULMONARY disease (COPD), ventilatory disturbance is caused by an increase in airway resistance and/or a loss of elastic recoil. The work of breathing is known to increase in COPD, and although three-quarters of the work is performed during inspiration, the remaining one-quarter is expended during expiration, which requires expiratory muscle contraction (17). Respiratory muscle fatigue is believed to be one of the factors that causes respiratory failure (14). Inspiratory muscle fatigue, especially that of the diaphragm, has been studied extensively by many authors (1,9,11,14,22, 26-28). In contrast, there have been only a few studies of expiratory muscle fatigue. Byrd and Hyatt (5) have reported that in COPD the strength of the expiratory muscles is not decreased. On the other hand, Rochester et al. (25) have shown that in COPD the strength of both expiratory and inspiratory muscles is decreased. Also, atrophy of the internal intercostal muscles has been demonstrated in COPD (6). However, little is known about the mechanisms involved in expiratory muscle fatigue, and no experimental study of expiratory muscle fatigue has been reported. Therefore, to investigate whether an increase in the work of breathing during expiration induces respiratory IN CHRONIC
2632
0161-7567191
$1.50
Copyright
muscle fatigue, a resistive load was applied on expiration in normal subjects, and the strength of both inspiratory and expiratory muscles was assessed. Movements of the chest wall and the electromyogram (EMG) of the rectus abdominis muscle were also monitored. METHODS
Eleven healthy male subjects familiar with respiratory maneuvers were recruited for the present study. Their average age was 28.3 t 2.0 (SD) yr, and none had a history of chronic respiratory, cardiovascular, or neuromuscular disease. All the subjects had normal spirometry and lung volumes and were studied while seated on a highbacked chair. Informed consent was obtained from all participants. Expiratory resistive loading was applied via three nonlinear resistances, which consisted of long Tygon tubes. The resistance loads were Rl = 24.5 cmH,O 0.5 1-l. s, R2 = 66.0 cmH,O 00.5 1-l. s, and R3 = 143 cmH,O.0.5 1-l. s. The resistances were calibrated at the flow rate of 0.5 l/s because the flow rate during loading was always ~0.5 l/s and the flow rate of 1.0 l/s was too high to allow measurement of these nonlinear resistances. One of the three resistances was connected to the expiratory port of a two-way breathing valve (model 1400, Hans Rudolph, Kansas City, MO). Each subject was asked to breathe through this expiratory resistance circuit until exhaustion or for no more than 60 min, using his own tidal volume and breathing frequency and wearing a noseclip. The flow was measured at the mouth with a heated pneumotachograph (Fleisch no. 1, Lausanne, Switzerland) and a differential pressure transducer (MP-45, Validyne, Northridge, CA); the volume was calculated by integration of the flow signal (model 1322, San-ei, Tokyo, Japan). Mouth pressure was measured at the mouthpiece by use of a differential pressure transducer (Validyne MP-45). In a preliminary experiment, a large resistance (R4 = 70.0 cmH,O 0.1 1-l s) was loaded on expiration. However, the endurance time was too short to induce expiratory muscle fatigue. Therefore we excluded the R4 loading from analysis. Static maximum inspiratory (PI,,) and expiratory (PE,,) pressures at the mouth were produced with a standard flanged mouthpiece connected to a metal tube, which contained a small air leak to prevent glottic closure, and to a tap that allowed the airway to be closed (3). expiration against the PE max was measured by maximal closed valve at total lung capacity (TLC) and functional residual capacity (FRC) with a differential pressure
0 1991 the American
l
l
Physiological
l
Society
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EXPIRATORY
MUSCLE
transducer (Validyne MP-45), while the subject was pressing his cheeks with his own hands. PI,, was measured at FRC and at residual volume (RV) in the same manner. During measurements of PI,, and PE,,, the subjects were verbally encouraged to achieve a maximum endurance. The determinations were repeated until three measurements varying by ~5% and sustained for 21 s were recorded; the highest value thus obtained was reported. In four subjects during R3 expiratory resistive loading, transdiaphragmatic pressure (Pdi) was assessed as the difference between gastric pressure and esophageal pressure, which were measured by two balloon-catheter systems; each balloon was 10 cm long with a 3.5cm perimeter (21). Phasic swings of Pdi were measured during both control and expiratory loaded breathing. Lung volumes were measured by a flow-type body plethysmograph (model 2800, Gould, Dayton, OH); the vital capacity (VC) and forced expired volume in 1 s (FE&) were obtained by use of a dry-seal spirometer (Spirotest-85, Chest, Tokyo). The thoracoabdominal configuration during R2 loading was monitored by six pairs of magnetometers (19) (SS-1237, Nihon-Kohden, Tokyo), and the output of each pair was displayed on a strip-chart recorder (Rectigraph-8K, San-ei, Tokyo). The anteroposterior and lateral diameters of the rib cage at the levels of the third intercostal space (AP-rib and LT-rib) and the xiphoid process (BP-xi and LT-xi) were measured. At a level 2 cm above the umbilicus, the abdominal anteroposterior and lateral diameters (AP-ab and LT-ab) were also obtained. The cross-sectional area at each level was calculated on the assumption that the thoracoabdominal configuration was an ellipse. Thus it was possible to assess changes in FRC from the cross-sectional area at each level during loaded breathing. The electrical activity of the rectus abdominis was assessed by recording the electromyogram (EMG) (model 1253A preamplifier, San-ei) with bipolar needle electrodes inserted near the right costal arch. During quiet breathing, the EMG activity of the abdominal muscle was negligible. The EMG of the rectus abdominis was measured during PE,, measurement and during expiratory loading. The EMG signal was filtered between 40 and 1,000 Hz (FV-664, NF Electronic Instruments, Yokohama, Japan), rectified, and integrated by a leaky integrator with a time constant of 100 ms (Eab) (model 1322, San-ei). The filtered EMG signal was recorded on a magnetic data recorder (A-67, Sony Magnescale, Tokyo) and then digitized at a rate of 1,000 samples/s with a minicomputer (PC-9801 VM4, NEC, Tokyo). Power spectral analysis of the EMG signal was performed by use of fast Fourier transform while the electrocardiogram QRS waveform was excluded manually. At the initial, middle, and end stages of the loaded breathing, the high-to-low frequency (H/L) ratio and the centroid frequency of at least five expirations were calculated and then averaged (8, 11, 28). The high-frequency band was set above, and the low-frequency band was set below the centroid frequency (9). The frequency band of the H/L was determined twice, from the power spectrum obtained at the initial stage of loading and at the control PE,, measurement, in each subject. The low- and high-fre-
FATIGUE
2633
quency band ranges were 40-266 and 326-500 Hz, respectively, during loaded breathing and 40-160 and 222-500 Hz for the recovery period. When there was any abrupt change in output of the power spectrum of the EMG, the data were excluded from analysis. Protocol. The study was performed on 4 different days (days 1-4) within 3 wk and at the same time of day on each occasion. On all test days, the subjects were asked to refrain from caffeine and alcohol for 12 h before the study. On each test day, the measurement of PI,, and PE m8x was repeated at least five times as a control measurement until a reproducible value was obtained. On days 1-3, the order of the resistances was randomized. On each day, after baseline lung volumes, PI,,, and PE m8x were obtained, control breathing was started and continued until the breathing pattern became stable. Then, expiratory loading with one of the three resistances (Rl-R3) was initiated and continued until exhaustion or for 60 min. Continuation of the loaded breathing was encouraged verbally. The end point (endurance time, Thm) was determined by the time the subject became intolerant of the loaded breathing and came off the mouthpiece. This occurred two or three breaths after the tidal volume decreased to one-half or two-thirds. During the recovery period, both PI,, and PE,, were measured at 1,5,10,15,30,45, and 60 min, but at 5 and 10 min, PE,, and PI,,, were measured at FRC only. In five subjects, the thoracoabdominal configuration and Eab were monitored for the R2 expiratory loading period and during the recovery period. On day 4, R2 was connected to the inspiratory port of the breathing valve, and the subject breathed through this inspiratory resistance in the same way as for the expiratory loading. All data were recorded on a strip-chart recorder and on a magnetic data recorder (A-67, Sony Magnescale) for later analysis of the EMG. All values given are means t SE. Statistical analyses were performed by use of Student’s t test and analysis of variance, and differences at P < 0.05 were considered significant. RESULTS
The baseline VC and FEV, of all subjects were within normal limits of the predicted values (7). The control PI max at FRC and RV was 115 t 9 and 118 t 9 cmH,O, respectively; the control PE,, at TLC and FRC was 173 t 12 and 150 t 11 cmH,O, respectively. A representative tracing for one subject during resistive loading is shown in Fig. 1. During expiratory loading, the expiratory time (TE) was lengthened greatly and the increase in the TE-to-total breathing cycle duration (TT) ratio (TE/ TT) was more pronounced at the higher resistances (P < 0.005; Table 1). During inspiratory loading, the inspiratory time (TI) was increased: TI/TT increased from 0.44 t 0.02 to 0.68 t 0.02 (P < 0.001). The tidal volume also increased by ~60% with all resistances (P < 0.05). The breathing frequency decreased to -45% of that in the control period (P < 0.005). Minute ventilation decreased to two-thirds of the control with all resistances (P < 0.01). Furthermore, mouth pressure (Pm) showed greater phasic swings with larger resistances. During expiratory loading at Rl, all subjects com-
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2634
EXPIRATORY
CONTROL
MUSCLE
EXP IRATORY
FATIGUE
LOADING end
AP
I
DIAMETER
25 r ‘”
”
=-
20
FIG. 1. Representative tracing of expiratory loaded breathing with R2. Upper and lower rib cages and abdominal anteroposterior (AP) diameters were measured at the level of the 3rd intercostal space (3rd ICS), xiphoid process (XI), and 2 cm above umbilicus (Ab). EMG was obtained from rectus abdominis. Pm, mouth pressure. Lung volume was obtained by integrating airflow signal. In this case, AP diameter at 3rd ICS increased by 9% and was higher than the average value [5.0 k 1.1% (SE)].
E M G (filtered)
E M G (integrated)
40 k”H20)
Pm
0 [
-
IMP. 1.0 L
VOLUME
[
Exp. c
1 30
stc
pleted the loaded breathing for 60 min. At R2, 5 of 11 subjects completed the 60-min run, and the Z’fi, of the other six subjects was 18.8 t 6.0 min (Fig. 2). At R3, only two of eight subjects completed the 60-min loading; the mean &, of the other six subjects was 23.6 t 4.5 min. On the other hand, during inspiratory loading at R2, four of nine subjects completed the 60-min loading regimen, and TABLE
1. Respiratory
the mean 5Vti, of the other five subjects was 16.7 t 6.1 min. There was no difference in the 5Vk, between the expiratory and inspiratory loadings at R2. No change was observed in either PE,,, or PI,, during the 60-min recovery period after Rl expiratory loaded breathing compared with the baseline values. After R2 loaded breathing, PE,, decreased and remained low
variables at control and during loaded breathing Minute
Frequency, Loading
Expiratory Rl R2
R3 Inspiratory R2
Control
breathsimin Loading
21.6t2.6
8.9&0.8$
22.2k1.9 19.lk2.3
9.9+1.1§ 7.2k1.35
22.0t2.3
10.4+1.7§
Tidal Volume,
liters
TE/TT
Pm, cmH,O
Ventilation, l/min
Control
Loading
Control
Loading
Loading
Control
Loading
0.6OkO.04 0.70t0.03 0.81kO.12
0.95+0.05§ 1.07kO. 14* l.llk0.12~
0.60t0.02 0.54kO.01 0.59t0.02
0.79&0.02§ 0.81~0.01~ 0.87*0.01
8.5t0.7 19.1t2.6 24.2t1.9
12.7kl.l 15.1kl.2
8.4&0.5$
12.2kl.l
7.2k0.57
0.95&O.
0.56t0.02
0.32+0.02§
17.7k2.3
8.5*0.9*
0.84tO.
11
15
Q
-38.225.0
Values are means k SE. TE, expiratory time; TT, total breathing cycle duration; Pm, averaged mouth pressure during expiration. with control by analysis of variance (ANOVA): * P < 0.05, t P -c 0.01, $ P < 0.005, $- P < 0.001.
9.3+0.7§
Compared
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EXPIRATORY
GO< 60
O88
o&p
O0
MUSCLE
000
__-------------------------------------------------------------
l
0
t
I
l
0 l I
l
.
a l
0 LJ,
I
Rl
1
R2
1
R3
EXPIRATORY LOADING FIG. 2. Endurance time during expiratory at different resistances. 0 and a, subjects breathing for 60 min and those who cbuld means k SD for those who could not complet
Ri
INSPIRATORY LOADING and inspiratory who completed not, respectively. le 60-min trial.
loading loaded Bars,
throughout the entire 60-min recovery period at both TLC and FRC (Fig. 3A). For the first 15 min after Et2 loaded breathing, PE,,, at both TLC and FRC of all subjects was 16% lower than that of control (P < 0.05) and remained low (P < 0.01) after 60 min of recovery. Those who completed the full 60-min loading tended to have a smaller decrease in PE,, than those who were unable to complete the full regimen. The PI,, at FRC of all subjects decreased by 13 and 7% at 1 and 30 min of the recovery period, respectively (P < 0.05); however, the PI mar at RV did not change at any time during recovery. After R3 expiratory loading, the PE,, (at TLC and FRC) of all subjects decreased maximally by -15% during the first 15 min of the recovery period (P < 0.05). This reduction persisted throughout the 60-min recovery period (Fig. 3B). The PI,, (at both FRC and RV) was also low throughout the first 15 min of the recovery period (P < 0.05). These decreases were greater than in R2 loading. Inspiratory loading with R2 resulted in a decrease in PI mEUlduring the first 15 min (P = 0.08), but PE,, was found to decrease at the 1 min only (P = 0.07). However, these changes were not significant statistically (Fig. 3C). The Eab began to increase greatly after the start of R2 expiratory loading. Although both Pm and Eab increased toward the end of loading, the ratio of Eab to Pm (Eab/ Pm) increased progressively during R2 expiratory loading. The mean increase at the end of the loading was 182 & 41% of the value at the initiation of loading (P < 0.01). The Eab during PE,, measurement decreased during the 1st min of the recovery period in four of the five subjects and from 5 to 60 min after loading was unchanged compared with that during the control PE,, measurement. The H/L ratio declined progressively during loading (P < O.Ol), and the mean decrease at the end of the loading was 44 t 11% of the value at its initiation (Fig. 4A). The centroid frequency changed similarly (P < 0.01). However, both the H/L ratio and the centroid fre-
FATIGUE
2635
quency during the recovery period did not differ from the control (Fig. 4B). During R2 expiratory loading, the FRC cross-sectional areas at the upper rib cage (AP-rib/Z X LT-rib/Z X K) and at the xiphoid level (AP-xi/2 X LT-xi/Z X a) increased by 5.3 t 1.7 and 7.7 t 2.7% (SE) of the control, respectively (both P < 0.05), and the AP diameters increased simultaneously by 5.0 t 1.1 and 5.5 t l.O%, respectively (both P < 0.005; Table 2). During recovery, however, there was no change in the cross-sectional area at either the upper rib cage or xiphoid level. The abdominal cross-sectional area also did not change during either loading or recovery periods. In R3 expiratory loading in four subjects, the Pdi swing during control quiet breathing was 8.5 t 1.9 cmH,O and increased to 28.3 t 7.0 cmH,O during loading (P c 0.05). The Pdi during control and loading was 6.9 t 1.2 and 22.2 t 3.5%, respectively, of the Pdi during the PI,, maneuver at FRC before loading. DISCUSSION
In the present study we have demonstrated that expiratory resistive loaded breathing can induce fatigue of expiratory muscles in normal subjects and that this fatigue persists for up to 60 min. The EMG suggests that the rectus abdominis can be fatigued by expiratory loading. Expiratory resistive loading also decreased inspiratory muscle strength. Thus the increased work of breathing on expiration may induce both expiratory and inspiratory muscle fatigue. C&hue in methodology. In the present study we chose PE maxp PI max, and abdominal EMG as indexes of respiratory muscle fatigue. PE,, and PI,, were measured by maximal voluntary maneuvers. It may be difficult to obtain a reproducible PE,, or PI,,, after a fatiguing run, because some fatigued subjects may come off the mouthpiece because of either discomfort or dyspnea. Such central components may influence the maximum pressures produced (PE,, or PI,, ) , especially those that come immediately after loading ceases. The decreases in both PE max and were greatest during the 1st min after p1max loading was completed. However, these decreases persisted up to 60 min, and no decrease in Eab during the PE max measurement was observed at 5-60 min during recovery. There are several questions, such as stability of EMG and quantitative EMG analysis. No saturation of raw EMG signals was observed from the amplifier throughout the experiment. The Eab during PE,,, measurement instantaneously reached a plateau throughout the experiment, although Eab during loading increased in a crescendo pattern in expiration (Fig. 1). The magnitude of the Eab did not change throughout the control and recovery periods except for the 1st min of recovery. These observations suggest that Eab at PE,,, measurement may faithfully reflect a maximal activation of the rectus abdominis throughout the experiment. Therefore it seems that central factors do not influence PE,,, or PI maxexcept immediately after loading is completed. Lung volume is an important determinant of maximum respiratory muscle force (i.e., PI,,, and PE,,,) (23). During R2 expiratory loading, FRC increased by -5%.
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2636
EXPIRATORY
A
2
0
MUSCLE
B
PEmax
80 -
PEmox
2 80 -
L *
0
CL
c= t3 w
FATIGUE
70 I
I
I
1
05 70av-0 -yt 6
EXP. LOAD R3
’
*
1 5 10 15
30
1
I
80
EXP. LOAD CONTROL
1
Plmax
Plmax
80
1 1 1 1
meanfSE 1 5 10 15
I 30
RECOVERY
I 45
EXP. LOAD I 60
TIME (min)
CONTROL
RECOVERY
45 TIME
60
(min)
3. Time course of maximum expiratory pressure (PE-) and maximum inspiratory pressure (PI-) after loaded breathing, expressed as percentages of respective control. n , 0, and A, respiratory pressures measured at total lung capacity (TLC), functional residual capacity (FRC), and residual volume (RV), respectively. A: expiratory loading with R2; B: expiratory loading with R3; and C: inspiratory loading with R2. Bars, means t SE. Compared with control values: *‘P < 0.05, tP < 0.01, $P < 0.005, $jP < 0.001. FIG.
During recovery, however, FRC was not different from that of the control. Therefore PE,, and PI,, at FRC during recovery may be comparable with the control. As a representative expiratory muscle, we chose the rectus abdominis. It is difficult to know the relative contributions of the abdominal muscles to expiration during expiratory loading. During expiratory loading, excursions of both AP and LT diameters of the abdomen were comparable, and both AP and LT diameters at end expiration during loading did not differ from the controls. The force of the rectus abdominis may balance that of the external oblique muscle during expiratory resistive loading, because it is known that the rectus abdominis decreases the AP diameter and that the external oblique muscle decreases the LT diameter (20). Although PE,, is mainly a measure of the strength of the abdominal muscles, the internal intercostal and other accessory muscles may also contribute. During expiratory loading, however, we observed a great increase in EMG activity and decreases in both the H/L ratio and the centroid frequency of the rectus abdominis. Furthermore, Eab/ Pm increased progressively during loading. These findings suggest that abdominal muscles, such as the rectus
abdominis, have a significant loaded breathing.
role during
expiratory
Loaded breathing and fatigue. Bellemare and Grassino (1) have shown that, in the diaphragm, fatigue can be predicted from a product of the duty cycle and the muscle tension (tension-time index, TTI). In the present study, the waveform of Pm was close to a square wave (Fig. l), and TE/TT was almost constant throughout loading. Following the method of Bellemare and Grassino, we calculated the TTI of the expiratory muscle as TE/TT X Pm/ PE maxat FRC, where Pm was the time-integrated mean value obtained during expiration. The expiratory TTIs of average breaths at loads Rl, R2, and R3 were 0.05 t 0.01, 0.11 t 0.02, and 0.16 t 0.02, respectively. Thus the expiratory TTI with Rl was lower than with R3 (P < 0.001). However, there were no significant differences in the expiratory TTI with R2 or R3 between subjects who completed the 60-min loading and those who could not. Furthermore, at any expiratory load, there was no significant correlation between the endurance time and the expiratory TTI or between the endurance time and the Pm/PE,, . On the other hand, with R2 inspiratory loading, the endurance time correlated inversely with the in-
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EXPIRATORY
C
MUSCLE
PEmox
100 -
2 80 0 c s c) 70dC + -0 %
INSP. LOAD , R2 I I I
llJ 5
1 1
Plmox
0 $00 OS CL
-
90
80 -
70
l
=
INSP. LOAD . ,
R2
CONTROL
mean?SE
I 1 I 1 1 5 10 15
I 30
RECOVERY FIG.
I 45
1 60
TIME (min)
3-Continued
TTI (r = -0.836, P < 0.01). However, there were several problems in evaluating expiratory TTI in this study. First, Pm was not, strictly speaking, a square wave. Second, Pm increased progressively during loading, whereas TE/TT was almost constant. Third, the end-expiratory lung volume during loading was higher than that at which the control PE,, was measured. Therefore further study should be done to define the TTI critical for expiratory muscle fatigue. When a skeletal muscle performs a fatiguing task, the EMG power spectrum shifts to a lower frequency (8,13). Gross et al. (11) have shown that, in the human diaphragm, the H/L ratio decreases linearly with contractility when breathing is done against a high inspiratory resistance. In the present study, Eab increased greatly from the start of expiratory loading. Furthermore, both the H/L ratio and the centroid frequency decreased toward the end of loaded breathing. Thus it is probable that during expiratory loading with R2 and R3 the abdominal muscles work hard and develop fatigue. During recovery, however, the power spectrum showed no fatigue pattern. Moxham et al. (22) have reported that, during submaximal contraction of the diaphragm, the H/L ratio decreased but did not change, relative to that before the submaximal contraction, during the recovery period in which low-frequency fatigue persisted for several hours. spiratory
FATIGUE
2637
Our finding of changes in the H/L ratio is in accord with the results of Moxham et al. However, it is unclear why the fatigue pattern of EMG does not continue after loading ceases. The cross-sectional areas of both the upper and lower rib cage increased during expiratory loading, but that of the abdomen did not change (Table 2). This increase in the cross-sectional area arose mainly from increases in the anteroposterior diameter. This is very similar to the finding of Martin et al. (16) that hyperinflation in response to expiratory loading is due largely to an increase in the volume of the rib cage compartment (6). In addition to expansion of the lower rib cage by diaphragmatic contraction, the lower rib cage expands by transmission of abdominal pressure through the area of apposition when the abdominal pressure increases (18). If stimulated in isolation, the rectus abdominis reduces the AP diameter of the rib cage, but the external oblique muscle decreases the LT diameter (20). In addition to the abdominal muscles, the internal intercostal and other expiratory muscles may assist in expiration during expiratory loading. Then, distortions of the rib cage may depend on the relative contraction of each muscle. Furthermore the pressure difference across the rib cage may influence the configuration of the rib cage. We are unable to estimate the relative contributions of each expiratory muscle to rib cage distortion, because we measured only EMG of the rectus abdominis. In addition to the decrease in PE,,,, PI,, also decreased, although to a lesser extent. TI decreased to - 1.5 s during expiratory loading with R2 or R3, and the tidal volume increased (Table 1). The phasic Pdi swing during expiratory loading increased 3.6-fold compared with that during control quiet breathing. This finding is consistent with a study by Martin et al. (see Fig. 3 in Ref. 16) showing that during expiratory resistive loading Pdi rose to -20 cmH,O in inspiration. Therefore the increase in the inspiratory flow rate may augment the work of the inspiratory muscles. On the other hand, at all expiratory loadings an increase in the cross-sectional area of the rib cage was observed. This increase suggests that the inspiratory muscles shortened, thus decreasing the inspiratory force generated according to the length-tension relationship in the inspiratory muscles (12). However, the length of the diaphragm was not thought to shorten during loading because there was no change in the abdominal cross-sectional area. The diaphragm was not at a disadvantageous position of its length-tension relationship. Therefore, shortening of the inspiratory muscles may contribute to the decrease in PI,, to a lesser extent. Diaphragmatic blood flow is inhibited by its contraction, and an increase in blood flow occurs during its relaxation phase (2). Diaphragmatic blood flow increases when breathing occurs against expiratory resistance (24). On the other hand, positive pressure around the diaphragm during contraction is reported to disturb its blood flow (4). Diaphragmatic blood flow can be impeded if pressure applied to the compliant compartment, i.e., capillaries and veins, is large enough and the duration of the applied pressure is long enough. In the present study, the Pm during expiration was 19 and 24 cmH,O with R2 and R3 expiratory loading, respectively, and TE (TE/
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2638
EXPIRATORY
A
RATIO
H/L
100
100
50
50
a > 0 -I a CENTROID FREQUENCY c -z iL 100
*
0 *
50
FATIGUE
.B RECOVERY PERIOD
DURING EXP. LOADING H/L
ILI 3 I
MUSCLE
0
RATIO
meon*SE n=5 I
I
1
1
I
1
I
1
I
CENTROID FREQUENCY
loo 50
0 MIDDLE
INITIAL
END
c
LOADED BREATHING
1
5
10
15
TT > 0.75) was long enough. Therefore, it is probable that positive pressure around the diaphragm during prolonged expiration decreased diaphragmatic blood flow and thus 0, delivery. Inspiratory loading with R2 caused only a slight decrease in both PE,,, and PI,,, during recovery; expiratory loading, with the same resistance, decreased PE,, and PI,, to a greater extent. FRC, however, did not change during inspiratory loading, suggesting that the 2. Thoracoabduminal configuration during expiratory loading with R2
at FRC
Recovery Period,min Loading Rib cage 3rd ICS AP LT Area Xiphoid AP LT Area Abdomen AP LT Area
1
15
30
60
105,0_+1*1~ 100.8~0.7 100.3tl.O lOO.lt0.5 105.3*1.7* 100.9kl.2
101.Otl.l 99.9kO.7 100.9k1.6
102.3k1.4 99.4kl.O 101.2k1.5
99.8kO.9 99.5kO.7 99.3k1.4
105.5+1.0t 102.1~2.0 107.7a2.7t
99.020.9 100.6t2.7 99.5k1.9
99.4k1.4 101.4*1.1 100.7t1.2
98.6tl.7 100.4tl.l 99.0t1.9
100.6t2.0 101.6k1.9 102.1+0.8 -
100.3t1.9 lOl.lt1.9 101.2k2.3
100.5*1.3 lOO.lkO.6 100.6k1.7
98.5~0.9 101.1t0.8 99.4k1.4
97.7k1.7 100.6kO.5 98.2t1.5
98.8k2.9 101.5t0.8 98.7k2.6
Values (means k SE) are expressed as percentage of control value obtained during quiet tidal breathing; n = 5. R2, moderate resistance; ICS, intercostal space; AP, anteroposterior diameter; LT, lateral diameter; Area, (AP/2) X (LT/2) X ?r. Compared with control (by ANOVA):
*P < 0.05, t P < 0.005.
45
60
TIME AFTER LOADING (min)
FTG. 4. II/L ratio (top) and centroid frequency (bottom) of abdominal EMG during R2 expiratory during PE,, measurement in recovery period (B). Values are expressed as a percentage of initial part value at control PE,, measurement (B). Compared with control: tP < 0.01, $P < 0.005.
TABLE
30
loading of loading
(A) and (A) or
diaphragm was not at mechanical disadvantage during inspiratory loading. Although the TTI of the inspiratory muscle cannot be evaluated exactly because of the nonsquare Pm waveform and because of a noncontrolled TI/ TT, the TTI calculated using the time-integrated mean Pm value and the mean TI/TT value was ~0.2 in one-half of the subjects. This TTI value was close to the critical fatigue threshold of the diaphragm, according to Bellemare and Grassino (1). Therefore, the magnitude of R2 may not always be large enough to induce inspiratory muscle fatigue. On the other hand, the abdominal muscles are reported to be recruited during inspiratory loading to facilitate inspiration (15). A small decrease in PE max was observed just after inspiratory loading, but this was not significant statistically. This slight decrease hPE,, may be due to a central component, because it recovered soon. As can be deduced from the pressure-volume diagram of Rahn et al. (23), PE,,, is maximal at TLC and then decreases as the lung volume decreases; our present data show a similar relationship between pressure and lung volume. In the present study, the subjects could not maintain a resting level FRC during expiratory loading, despite a prolonged TE. Thus FRC increased as the expiratory resistance increased to allow the expiratory muscles to increase the expiratory force generated. Expiratory loading is known to change the ventilatory pattern by slowing the breathing frequency and increasing the tidal volume (10). During expiratory loading with Rl, R2, and R3, breathing frequency decreased by 55%, and the tidal volume increased by 60%. TE/TT increased with larger resistances. Thus the respiratory pattern
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EXPIRATORY
MUSCLE
adapts to an increase in the expiratory work of breathing by optimizing the pressure-volume relationships in breathing to allow expiratory muscles to generate greater forces. Furthermore, the increase in FRC during expiratory loading may take advantage of passive recoil of the respiratory system, reducing the increased work of the expiratory muscles caused by the external resistance. In summary, expiratory resistive loaded breathing induces muscle fatigue in both expiratory and inspiratory muscles. Also, as reported by previous authors (1, 9, 11, 14,22,26,27), inspiratory loaded breathing causes inspiratory muscle fatigue. Thus it is possible that, in obstructive pulmonary diseases, airway obstruction may contribute to fatigue of both inspiratory and expiratory muscles. The authors thank Dr. James P. Butler for helpful advice in preparing the manuscript. Address for reprint requests: S. Suzuki, First Dept. of Internal Meditine, Yokohama’ City University School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236, Japan. I
Received 27 September 1989; accepted in final form 6 February
1991.
GARRARD, C. S., AND D. J. LANE. The pattern of stimulated breathing in man during non-elastic expiratory loading. J. Physiol. Land 279: 17-29,1978. 11. GROSS, D., A. GRASSINO, W. R. D. Ross, AND P. T. MACKLEM. Electromyogram pattern of diaphragmatic fatigue. _ - J. Appl. Physiol. 46: l-7, i979. 12. KIM, M. J., W. S. DRUZ, J. DANON, W. MACHNACH, AND J. T. SHARP. Mechanics of the canine diaphragm. J. Appl. Physiol. 41: 369-382,1976. 13. KOGI, K., AND
T. HAKAMAD A. Slowing of Surface electromyogram and muscle strength in muscle fatigue. Rep. Inst. Sci. Labour Tokyo
60: 27-41,1962. 14. MACKLEM, P.
T., AND C. S. Roussos. Respiratory muscle fatigue: a cause of resniratorv failure? Clin. Sci. Mol. Med. 53: 419-422.1977. * 15. MARTIN, J. G., AN;) A. DE TROYER. The behaviour of the abdominal muscles during inspiratory mechanical loading. Respir. Physiol. 50: 63-73,1982. 16. MARTIN, J.
G., M. HABIB, AND L. A. ENGEL. Inspiratory muscle activity during induced hyperinflation. Respir. Physiol. 39: 303-
313,198O. 17. MCILORY, 18. 19.
F., AND A. GRASSINO. Effect of pressure and timing of on human diaphragm fatigue. J. Appl. Physiol. 53:
20.
F., D. WIGHT, C. M. LAVIGNE, AND A. GRASSINO. Effect of tension and timing of contraction on the blood flow of the diaphragm. J. Appl. Physiol. 54: 1597-1606,1983. 3, BLACK. L. F.. AND R. E. HYATT. Maximal respirator-v pressures: normal values and relationship to age and sex. Am. Rev. Respir. Dis. 99: 696-702,1969. 4. BUCHLER, B., S. MAGDER, H. KATSARDIS, Y. JAMMES, AND C. ROUSSOS. Effects of pleural pressure on diaphragmatic blood flow. J. Appl. Physiol. 58: 691-697, 1985. 5. BYRD. R. B., AND R. E. HYATT. Maximal respiratory pressures in chronic obst’ructive lung disease. Am. Rev. Respir. DE. 98: 848-856,
21.
contraction 1190-1195,1982. 2. BELLEMARE,
~
I
I
1968. 6. CAMPBELL, J. T. W. SHIELDS.
-
a
A., R. L. HUGHES, V. SAHGAL, J. FREDERIKSEN, AND Alternations in intercostal muscle morphology and in patients with obstructive lung disease. Am. Rev.
biochemistry Respir. Dis. 122: 679-686, 1980. 7. COTES, J. E. Lung Function; Assessment and Application in Medicine (4th ed.). Oxford, UK: Blackwell, 1979, p. 329-387. 8. EDWARDS, R. H. T. Physiological analysis of skeletal muscle weakness and fatigue. Clin. Sci. Mol. Med. 54: 463-470, 1978. 9. FITTING, J. W., T. D. BRADLEY, P. A. EASTON, M. J. LINCOLN, M, D. GOLDMAN, AND A. GRASSINO. Dissociation between diaphragmatic and rib cage muscle fatigue. J. Appl. Physiol. 64: 959-965, 1988.
2639
10.
REFERENCES 1, BELLEMARE,
FATIGUE
22.
23.
24.
25.
26.
27. 28.
M. B., AND R. V. CHRISTIE. The work of breathing in emphysema. Clin. Sci. Lond. 13: 147-154, 1954. MEAD, J. Functional significance of the area of apposition of diaphragm to rib cage. Am. Rev. Respir. Dis. 119: 31-32, 1979. MEAD, J., N. PETERSON, G. GRIMBY, AND J. MEAD. Pulmonary ventilation measured from body surface movements. Science Wash. DC 156: 1383-1384,1967. MIER, A., C. BROPHY, M. ESTENNE, J. MOXHAM, M. GREEN, AND A. DE TROYER. Action of abdominal muscles on rib cage - in humans. J. Appl. Physiol. 58: 1438-1443,1985. MILIC-EMILI, J., J. MEAD, J. M. TURNER, AND E. M. GLAUSER. Improved technique for estimating pleural pressure from esophageal balloons. J. Appl. Physiol. 19: 207-211, 1964. MOXHAM, J., R. H. T. EDWARDS, M. AUBIER, A. DE TROYER, G. FARKAS. P. T. MACKLEM, AND C. Roussos. Changes in EMG power spectrum (high-to-low ratio) with force fatigue in humans. J. Appl. Physiol. 53: 1094-1099, 1982. RAHN, H., A. B. OTIS, L. E. CHADWICK, AND W. 0. FENN. The pressure-volume diagram of the thorax and lung. Am. J. Physiol. 146: 161-178,1946. ROBERTSON, C.
H. JR., W. L. ESCHENBACHER, AND R. L. JOHNSON, JR. Respiratory muscle blood flow distribution during expiratory resistance. J. C&n. Invest. 60: 473-480, 1977. ROCHESTER, D. F., N. M. BRAUN, AND N. S. ARORA. Respiratory muscle strength in chronic obstructive pulmonary disease. Am. Rev. Respir. Dis. 119: 151-154, 1979. ROUSSOS, C. S., M. FIXLEY, D. GROSS, AND P. T. MACKLEM. Fatigue of inspiratory muscles and their synergic behavior. J. Appl. Physiol. 46: 897-904,1979. R&SSOS, C. S., AND P. T. MACKLEM. Diaphragmatic fatigue in man. J. ADDS. Physiol. 43: 189-197, 1977. SIECK, G.?., A. %IAZAR, AND M. J.‘BELMAN. Changes in diaphragmatic EMG spectra during hyperpneic loads. Respir. Physiol. 61: 137-152,1985.
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muscle fatigue in normal subjects
SHUNSUKE SUZUKI, JUNNICHI SUZUKI, AND TAKAO OKUBO First Department of Internal Medicine, Yokohama City University School of Medicine, Yokohama 232, Japan
SUZUKI,
SHUNSUKE,
JUNNICHI
SUZUKI,
AND
TAKAO
OKUBO.
Expiratory muscle fatigue in normal subjects. J. Appl. Physiol. 70(6): 2632-2639, 1991.-We examined expiratory muscle fatigue during expiratory resistive loading in 11 normal subjects. Subjects breathed against expiratory resistances at their own breathing frequency and tidal volume until exhaustion or for 60 min. Respiratory muscle strength was assessed from both the maximum static expiratory and inspiratory mouth pressures (PE mEu and PI,,). At the lowest resistance, PE,, and PI,, measured after completion of the expiratory loaded breathing were not different from control values. With higher resistance, both PE,, and PI,, were decreased (P < 0.05), and the decrease lasted for 260 min. The electromyogram high-to-low frequency power ratio for the rectus abdominis muscle decreased progressively during loading (P < O.Ol), but the integrated EMG activity did not change during recovery. Transdiaphragmatic pressure during loading was increased 3.6-fold compared with control (P < 0.05). These findings suggest that expiratory resistive loaded breathing induces muscle fatigue in both expiratory and inspiratory muscles, Fatigue of the expiratory muscles can be attributed directly to the high work load and that of the inspiratory muscles may be related to increased work due to shortened inspiratory time. resistive dominal
loaded breathing; muscles
maximum
expiratory
pressure;
ab-
OBSTRUCTIVE PULMONARY disease (COPD), ventilatory disturbance is caused by an increase in airway resistance and/or a loss of elastic recoil. The work of breathing is known to increase in COPD, and although three-quarters of the work is performed during inspiration, the remaining one-quarter is expended during expiration, which requires expiratory muscle contraction (17). Respiratory muscle fatigue is believed to be one of the factors that causes respiratory failure (14). Inspiratory muscle fatigue, especially that of the diaphragm, has been studied extensively by many authors (1,9,11,14,22, 26-28). In contrast, there have been only a few studies of expiratory muscle fatigue. Byrd and Hyatt (5) have reported that in COPD the strength of the expiratory muscles is not decreased. On the other hand, Rochester et al. (25) have shown that in COPD the strength of both expiratory and inspiratory muscles is decreased. Also, atrophy of the internal intercostal muscles has been demonstrated in COPD (6). However, little is known about the mechanisms involved in expiratory muscle fatigue, and no experimental study of expiratory muscle fatigue has been reported. Therefore, to investigate whether an increase in the work of breathing during expiration induces respiratory IN CHRONIC
2632
0161-7567191
$1.50
Copyright
muscle fatigue, a resistive load was applied on expiration in normal subjects, and the strength of both inspiratory and expiratory muscles was assessed. Movements of the chest wall and the electromyogram (EMG) of the rectus abdominis muscle were also monitored. METHODS
Eleven healthy male subjects familiar with respiratory maneuvers were recruited for the present study. Their average age was 28.3 t 2.0 (SD) yr, and none had a history of chronic respiratory, cardiovascular, or neuromuscular disease. All the subjects had normal spirometry and lung volumes and were studied while seated on a highbacked chair. Informed consent was obtained from all participants. Expiratory resistive loading was applied via three nonlinear resistances, which consisted of long Tygon tubes. The resistance loads were Rl = 24.5 cmH,O 0.5 1-l. s, R2 = 66.0 cmH,O 00.5 1-l. s, and R3 = 143 cmH,O.0.5 1-l. s. The resistances were calibrated at the flow rate of 0.5 l/s because the flow rate during loading was always ~0.5 l/s and the flow rate of 1.0 l/s was too high to allow measurement of these nonlinear resistances. One of the three resistances was connected to the expiratory port of a two-way breathing valve (model 1400, Hans Rudolph, Kansas City, MO). Each subject was asked to breathe through this expiratory resistance circuit until exhaustion or for no more than 60 min, using his own tidal volume and breathing frequency and wearing a noseclip. The flow was measured at the mouth with a heated pneumotachograph (Fleisch no. 1, Lausanne, Switzerland) and a differential pressure transducer (MP-45, Validyne, Northridge, CA); the volume was calculated by integration of the flow signal (model 1322, San-ei, Tokyo, Japan). Mouth pressure was measured at the mouthpiece by use of a differential pressure transducer (Validyne MP-45). In a preliminary experiment, a large resistance (R4 = 70.0 cmH,O 0.1 1-l s) was loaded on expiration. However, the endurance time was too short to induce expiratory muscle fatigue. Therefore we excluded the R4 loading from analysis. Static maximum inspiratory (PI,,) and expiratory (PE,,) pressures at the mouth were produced with a standard flanged mouthpiece connected to a metal tube, which contained a small air leak to prevent glottic closure, and to a tap that allowed the airway to be closed (3). expiration against the PE max was measured by maximal closed valve at total lung capacity (TLC) and functional residual capacity (FRC) with a differential pressure
0 1991 the American
l
l
Physiological
l
Society
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EXPIRATORY
MUSCLE
transducer (Validyne MP-45), while the subject was pressing his cheeks with his own hands. PI,, was measured at FRC and at residual volume (RV) in the same manner. During measurements of PI,, and PE,,, the subjects were verbally encouraged to achieve a maximum endurance. The determinations were repeated until three measurements varying by ~5% and sustained for 21 s were recorded; the highest value thus obtained was reported. In four subjects during R3 expiratory resistive loading, transdiaphragmatic pressure (Pdi) was assessed as the difference between gastric pressure and esophageal pressure, which were measured by two balloon-catheter systems; each balloon was 10 cm long with a 3.5cm perimeter (21). Phasic swings of Pdi were measured during both control and expiratory loaded breathing. Lung volumes were measured by a flow-type body plethysmograph (model 2800, Gould, Dayton, OH); the vital capacity (VC) and forced expired volume in 1 s (FE&) were obtained by use of a dry-seal spirometer (Spirotest-85, Chest, Tokyo). The thoracoabdominal configuration during R2 loading was monitored by six pairs of magnetometers (19) (SS-1237, Nihon-Kohden, Tokyo), and the output of each pair was displayed on a strip-chart recorder (Rectigraph-8K, San-ei, Tokyo). The anteroposterior and lateral diameters of the rib cage at the levels of the third intercostal space (AP-rib and LT-rib) and the xiphoid process (BP-xi and LT-xi) were measured. At a level 2 cm above the umbilicus, the abdominal anteroposterior and lateral diameters (AP-ab and LT-ab) were also obtained. The cross-sectional area at each level was calculated on the assumption that the thoracoabdominal configuration was an ellipse. Thus it was possible to assess changes in FRC from the cross-sectional area at each level during loaded breathing. The electrical activity of the rectus abdominis was assessed by recording the electromyogram (EMG) (model 1253A preamplifier, San-ei) with bipolar needle electrodes inserted near the right costal arch. During quiet breathing, the EMG activity of the abdominal muscle was negligible. The EMG of the rectus abdominis was measured during PE,, measurement and during expiratory loading. The EMG signal was filtered between 40 and 1,000 Hz (FV-664, NF Electronic Instruments, Yokohama, Japan), rectified, and integrated by a leaky integrator with a time constant of 100 ms (Eab) (model 1322, San-ei). The filtered EMG signal was recorded on a magnetic data recorder (A-67, Sony Magnescale, Tokyo) and then digitized at a rate of 1,000 samples/s with a minicomputer (PC-9801 VM4, NEC, Tokyo). Power spectral analysis of the EMG signal was performed by use of fast Fourier transform while the electrocardiogram QRS waveform was excluded manually. At the initial, middle, and end stages of the loaded breathing, the high-to-low frequency (H/L) ratio and the centroid frequency of at least five expirations were calculated and then averaged (8, 11, 28). The high-frequency band was set above, and the low-frequency band was set below the centroid frequency (9). The frequency band of the H/L was determined twice, from the power spectrum obtained at the initial stage of loading and at the control PE,, measurement, in each subject. The low- and high-fre-
FATIGUE
2633
quency band ranges were 40-266 and 326-500 Hz, respectively, during loaded breathing and 40-160 and 222-500 Hz for the recovery period. When there was any abrupt change in output of the power spectrum of the EMG, the data were excluded from analysis. Protocol. The study was performed on 4 different days (days 1-4) within 3 wk and at the same time of day on each occasion. On all test days, the subjects were asked to refrain from caffeine and alcohol for 12 h before the study. On each test day, the measurement of PI,, and PE m8x was repeated at least five times as a control measurement until a reproducible value was obtained. On days 1-3, the order of the resistances was randomized. On each day, after baseline lung volumes, PI,,, and PE m8x were obtained, control breathing was started and continued until the breathing pattern became stable. Then, expiratory loading with one of the three resistances (Rl-R3) was initiated and continued until exhaustion or for 60 min. Continuation of the loaded breathing was encouraged verbally. The end point (endurance time, Thm) was determined by the time the subject became intolerant of the loaded breathing and came off the mouthpiece. This occurred two or three breaths after the tidal volume decreased to one-half or two-thirds. During the recovery period, both PI,, and PE,, were measured at 1,5,10,15,30,45, and 60 min, but at 5 and 10 min, PE,, and PI,,, were measured at FRC only. In five subjects, the thoracoabdominal configuration and Eab were monitored for the R2 expiratory loading period and during the recovery period. On day 4, R2 was connected to the inspiratory port of the breathing valve, and the subject breathed through this inspiratory resistance in the same way as for the expiratory loading. All data were recorded on a strip-chart recorder and on a magnetic data recorder (A-67, Sony Magnescale) for later analysis of the EMG. All values given are means t SE. Statistical analyses were performed by use of Student’s t test and analysis of variance, and differences at P < 0.05 were considered significant. RESULTS
The baseline VC and FEV, of all subjects were within normal limits of the predicted values (7). The control PI max at FRC and RV was 115 t 9 and 118 t 9 cmH,O, respectively; the control PE,, at TLC and FRC was 173 t 12 and 150 t 11 cmH,O, respectively. A representative tracing for one subject during resistive loading is shown in Fig. 1. During expiratory loading, the expiratory time (TE) was lengthened greatly and the increase in the TE-to-total breathing cycle duration (TT) ratio (TE/ TT) was more pronounced at the higher resistances (P < 0.005; Table 1). During inspiratory loading, the inspiratory time (TI) was increased: TI/TT increased from 0.44 t 0.02 to 0.68 t 0.02 (P < 0.001). The tidal volume also increased by ~60% with all resistances (P < 0.05). The breathing frequency decreased to -45% of that in the control period (P < 0.005). Minute ventilation decreased to two-thirds of the control with all resistances (P < 0.01). Furthermore, mouth pressure (Pm) showed greater phasic swings with larger resistances. During expiratory loading at Rl, all subjects com-
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2634
EXPIRATORY
CONTROL
MUSCLE
EXP IRATORY
FATIGUE
LOADING end
AP
I
DIAMETER
25 r ‘”
”
=-
20
FIG. 1. Representative tracing of expiratory loaded breathing with R2. Upper and lower rib cages and abdominal anteroposterior (AP) diameters were measured at the level of the 3rd intercostal space (3rd ICS), xiphoid process (XI), and 2 cm above umbilicus (Ab). EMG was obtained from rectus abdominis. Pm, mouth pressure. Lung volume was obtained by integrating airflow signal. In this case, AP diameter at 3rd ICS increased by 9% and was higher than the average value [5.0 k 1.1% (SE)].
E M G (filtered)
E M G (integrated)
40 k”H20)
Pm
0 [
-
IMP. 1.0 L
VOLUME
[
Exp. c
1 30
stc
pleted the loaded breathing for 60 min. At R2, 5 of 11 subjects completed the 60-min run, and the Z’fi, of the other six subjects was 18.8 t 6.0 min (Fig. 2). At R3, only two of eight subjects completed the 60-min loading; the mean &, of the other six subjects was 23.6 t 4.5 min. On the other hand, during inspiratory loading at R2, four of nine subjects completed the 60-min loading regimen, and TABLE
1. Respiratory
the mean 5Vti, of the other five subjects was 16.7 t 6.1 min. There was no difference in the 5Vk, between the expiratory and inspiratory loadings at R2. No change was observed in either PE,,, or PI,, during the 60-min recovery period after Rl expiratory loaded breathing compared with the baseline values. After R2 loaded breathing, PE,, decreased and remained low
variables at control and during loaded breathing Minute
Frequency, Loading
Expiratory Rl R2
R3 Inspiratory R2
Control
breathsimin Loading
21.6t2.6
8.9&0.8$
22.2k1.9 19.lk2.3
9.9+1.1§ 7.2k1.35
22.0t2.3
10.4+1.7§
Tidal Volume,
liters
TE/TT
Pm, cmH,O
Ventilation, l/min
Control
Loading
Control
Loading
Loading
Control
Loading
0.6OkO.04 0.70t0.03 0.81kO.12
0.95+0.05§ 1.07kO. 14* l.llk0.12~
0.60t0.02 0.54kO.01 0.59t0.02
0.79&0.02§ 0.81~0.01~ 0.87*0.01
8.5t0.7 19.1t2.6 24.2t1.9
12.7kl.l 15.1kl.2
8.4&0.5$
12.2kl.l
7.2k0.57
0.95&O.
0.56t0.02
0.32+0.02§
17.7k2.3
8.5*0.9*
0.84tO.
11
15
Q
-38.225.0
Values are means k SE. TE, expiratory time; TT, total breathing cycle duration; Pm, averaged mouth pressure during expiration. with control by analysis of variance (ANOVA): * P < 0.05, t P -c 0.01, $ P < 0.005, $- P < 0.001.
9.3+0.7§
Compared
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EXPIRATORY
GO< 60
O88
o&p
O0
MUSCLE
000
__-------------------------------------------------------------
l
0
t
I
l
0 l I
l
.
a l
0 LJ,
I
Rl
1
R2
1
R3
EXPIRATORY LOADING FIG. 2. Endurance time during expiratory at different resistances. 0 and a, subjects breathing for 60 min and those who cbuld means k SD for those who could not complet
Ri
INSPIRATORY LOADING and inspiratory who completed not, respectively. le 60-min trial.
loading loaded Bars,
throughout the entire 60-min recovery period at both TLC and FRC (Fig. 3A). For the first 15 min after Et2 loaded breathing, PE,,, at both TLC and FRC of all subjects was 16% lower than that of control (P < 0.05) and remained low (P < 0.01) after 60 min of recovery. Those who completed the full 60-min loading tended to have a smaller decrease in PE,, than those who were unable to complete the full regimen. The PI,, at FRC of all subjects decreased by 13 and 7% at 1 and 30 min of the recovery period, respectively (P < 0.05); however, the PI mar at RV did not change at any time during recovery. After R3 expiratory loading, the PE,, (at TLC and FRC) of all subjects decreased maximally by -15% during the first 15 min of the recovery period (P < 0.05). This reduction persisted throughout the 60-min recovery period (Fig. 3B). The PI,, (at both FRC and RV) was also low throughout the first 15 min of the recovery period (P < 0.05). These decreases were greater than in R2 loading. Inspiratory loading with R2 resulted in a decrease in PI mEUlduring the first 15 min (P = 0.08), but PE,, was found to decrease at the 1 min only (P = 0.07). However, these changes were not significant statistically (Fig. 3C). The Eab began to increase greatly after the start of R2 expiratory loading. Although both Pm and Eab increased toward the end of loading, the ratio of Eab to Pm (Eab/ Pm) increased progressively during R2 expiratory loading. The mean increase at the end of the loading was 182 & 41% of the value at the initiation of loading (P < 0.01). The Eab during PE,, measurement decreased during the 1st min of the recovery period in four of the five subjects and from 5 to 60 min after loading was unchanged compared with that during the control PE,, measurement. The H/L ratio declined progressively during loading (P < O.Ol), and the mean decrease at the end of the loading was 44 t 11% of the value at its initiation (Fig. 4A). The centroid frequency changed similarly (P < 0.01). However, both the H/L ratio and the centroid fre-
FATIGUE
2635
quency during the recovery period did not differ from the control (Fig. 4B). During R2 expiratory loading, the FRC cross-sectional areas at the upper rib cage (AP-rib/Z X LT-rib/Z X K) and at the xiphoid level (AP-xi/2 X LT-xi/Z X a) increased by 5.3 t 1.7 and 7.7 t 2.7% (SE) of the control, respectively (both P < 0.05), and the AP diameters increased simultaneously by 5.0 t 1.1 and 5.5 t l.O%, respectively (both P < 0.005; Table 2). During recovery, however, there was no change in the cross-sectional area at either the upper rib cage or xiphoid level. The abdominal cross-sectional area also did not change during either loading or recovery periods. In R3 expiratory loading in four subjects, the Pdi swing during control quiet breathing was 8.5 t 1.9 cmH,O and increased to 28.3 t 7.0 cmH,O during loading (P c 0.05). The Pdi during control and loading was 6.9 t 1.2 and 22.2 t 3.5%, respectively, of the Pdi during the PI,, maneuver at FRC before loading. DISCUSSION
In the present study we have demonstrated that expiratory resistive loaded breathing can induce fatigue of expiratory muscles in normal subjects and that this fatigue persists for up to 60 min. The EMG suggests that the rectus abdominis can be fatigued by expiratory loading. Expiratory resistive loading also decreased inspiratory muscle strength. Thus the increased work of breathing on expiration may induce both expiratory and inspiratory muscle fatigue. C&hue in methodology. In the present study we chose PE maxp PI max, and abdominal EMG as indexes of respiratory muscle fatigue. PE,, and PI,, were measured by maximal voluntary maneuvers. It may be difficult to obtain a reproducible PE,, or PI,,, after a fatiguing run, because some fatigued subjects may come off the mouthpiece because of either discomfort or dyspnea. Such central components may influence the maximum pressures produced (PE,, or PI,, ) , especially those that come immediately after loading ceases. The decreases in both PE max and were greatest during the 1st min after p1max loading was completed. However, these decreases persisted up to 60 min, and no decrease in Eab during the PE max measurement was observed at 5-60 min during recovery. There are several questions, such as stability of EMG and quantitative EMG analysis. No saturation of raw EMG signals was observed from the amplifier throughout the experiment. The Eab during PE,,, measurement instantaneously reached a plateau throughout the experiment, although Eab during loading increased in a crescendo pattern in expiration (Fig. 1). The magnitude of the Eab did not change throughout the control and recovery periods except for the 1st min of recovery. These observations suggest that Eab at PE,,, measurement may faithfully reflect a maximal activation of the rectus abdominis throughout the experiment. Therefore it seems that central factors do not influence PE,,, or PI maxexcept immediately after loading is completed. Lung volume is an important determinant of maximum respiratory muscle force (i.e., PI,,, and PE,,,) (23). During R2 expiratory loading, FRC increased by -5%.
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2636
EXPIRATORY
A
2
0
MUSCLE
B
PEmax
80 -
PEmox
2 80 -
L *
0
CL
c= t3 w
FATIGUE
70 I
I
I
1
05 70av-0 -yt 6
EXP. LOAD R3
’
*
1 5 10 15
30
1
I
80
EXP. LOAD CONTROL
1
Plmax
Plmax
80
1 1 1 1
meanfSE 1 5 10 15
I 30
RECOVERY
I 45
EXP. LOAD I 60
TIME (min)
CONTROL
RECOVERY
45 TIME
60
(min)
3. Time course of maximum expiratory pressure (PE-) and maximum inspiratory pressure (PI-) after loaded breathing, expressed as percentages of respective control. n , 0, and A, respiratory pressures measured at total lung capacity (TLC), functional residual capacity (FRC), and residual volume (RV), respectively. A: expiratory loading with R2; B: expiratory loading with R3; and C: inspiratory loading with R2. Bars, means t SE. Compared with control values: *‘P < 0.05, tP < 0.01, $P < 0.005, $jP < 0.001. FIG.
During recovery, however, FRC was not different from that of the control. Therefore PE,, and PI,, at FRC during recovery may be comparable with the control. As a representative expiratory muscle, we chose the rectus abdominis. It is difficult to know the relative contributions of the abdominal muscles to expiration during expiratory loading. During expiratory loading, excursions of both AP and LT diameters of the abdomen were comparable, and both AP and LT diameters at end expiration during loading did not differ from the controls. The force of the rectus abdominis may balance that of the external oblique muscle during expiratory resistive loading, because it is known that the rectus abdominis decreases the AP diameter and that the external oblique muscle decreases the LT diameter (20). Although PE,, is mainly a measure of the strength of the abdominal muscles, the internal intercostal and other accessory muscles may also contribute. During expiratory loading, however, we observed a great increase in EMG activity and decreases in both the H/L ratio and the centroid frequency of the rectus abdominis. Furthermore, Eab/ Pm increased progressively during loading. These findings suggest that abdominal muscles, such as the rectus
abdominis, have a significant loaded breathing.
role during
expiratory
Loaded breathing and fatigue. Bellemare and Grassino (1) have shown that, in the diaphragm, fatigue can be predicted from a product of the duty cycle and the muscle tension (tension-time index, TTI). In the present study, the waveform of Pm was close to a square wave (Fig. l), and TE/TT was almost constant throughout loading. Following the method of Bellemare and Grassino, we calculated the TTI of the expiratory muscle as TE/TT X Pm/ PE maxat FRC, where Pm was the time-integrated mean value obtained during expiration. The expiratory TTIs of average breaths at loads Rl, R2, and R3 were 0.05 t 0.01, 0.11 t 0.02, and 0.16 t 0.02, respectively. Thus the expiratory TTI with Rl was lower than with R3 (P < 0.001). However, there were no significant differences in the expiratory TTI with R2 or R3 between subjects who completed the 60-min loading and those who could not. Furthermore, at any expiratory load, there was no significant correlation between the endurance time and the expiratory TTI or between the endurance time and the Pm/PE,, . On the other hand, with R2 inspiratory loading, the endurance time correlated inversely with the in-
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EXPIRATORY
C
MUSCLE
PEmox
100 -
2 80 0 c s c) 70dC + -0 %
INSP. LOAD , R2 I I I
llJ 5
1 1
Plmox
0 $00 OS CL
-
90
80 -
70
l
=
INSP. LOAD . ,
R2
CONTROL
mean?SE
I 1 I 1 1 5 10 15
I 30
RECOVERY FIG.
I 45
1 60
TIME (min)
3-Continued
TTI (r = -0.836, P < 0.01). However, there were several problems in evaluating expiratory TTI in this study. First, Pm was not, strictly speaking, a square wave. Second, Pm increased progressively during loading, whereas TE/TT was almost constant. Third, the end-expiratory lung volume during loading was higher than that at which the control PE,, was measured. Therefore further study should be done to define the TTI critical for expiratory muscle fatigue. When a skeletal muscle performs a fatiguing task, the EMG power spectrum shifts to a lower frequency (8,13). Gross et al. (11) have shown that, in the human diaphragm, the H/L ratio decreases linearly with contractility when breathing is done against a high inspiratory resistance. In the present study, Eab increased greatly from the start of expiratory loading. Furthermore, both the H/L ratio and the centroid frequency decreased toward the end of loaded breathing. Thus it is probable that during expiratory loading with R2 and R3 the abdominal muscles work hard and develop fatigue. During recovery, however, the power spectrum showed no fatigue pattern. Moxham et al. (22) have reported that, during submaximal contraction of the diaphragm, the H/L ratio decreased but did not change, relative to that before the submaximal contraction, during the recovery period in which low-frequency fatigue persisted for several hours. spiratory
FATIGUE
2637
Our finding of changes in the H/L ratio is in accord with the results of Moxham et al. However, it is unclear why the fatigue pattern of EMG does not continue after loading ceases. The cross-sectional areas of both the upper and lower rib cage increased during expiratory loading, but that of the abdomen did not change (Table 2). This increase in the cross-sectional area arose mainly from increases in the anteroposterior diameter. This is very similar to the finding of Martin et al. (16) that hyperinflation in response to expiratory loading is due largely to an increase in the volume of the rib cage compartment (6). In addition to expansion of the lower rib cage by diaphragmatic contraction, the lower rib cage expands by transmission of abdominal pressure through the area of apposition when the abdominal pressure increases (18). If stimulated in isolation, the rectus abdominis reduces the AP diameter of the rib cage, but the external oblique muscle decreases the LT diameter (20). In addition to the abdominal muscles, the internal intercostal and other expiratory muscles may assist in expiration during expiratory loading. Then, distortions of the rib cage may depend on the relative contraction of each muscle. Furthermore the pressure difference across the rib cage may influence the configuration of the rib cage. We are unable to estimate the relative contributions of each expiratory muscle to rib cage distortion, because we measured only EMG of the rectus abdominis. In addition to the decrease in PE,,,, PI,, also decreased, although to a lesser extent. TI decreased to - 1.5 s during expiratory loading with R2 or R3, and the tidal volume increased (Table 1). The phasic Pdi swing during expiratory loading increased 3.6-fold compared with that during control quiet breathing. This finding is consistent with a study by Martin et al. (see Fig. 3 in Ref. 16) showing that during expiratory resistive loading Pdi rose to -20 cmH,O in inspiration. Therefore the increase in the inspiratory flow rate may augment the work of the inspiratory muscles. On the other hand, at all expiratory loadings an increase in the cross-sectional area of the rib cage was observed. This increase suggests that the inspiratory muscles shortened, thus decreasing the inspiratory force generated according to the length-tension relationship in the inspiratory muscles (12). However, the length of the diaphragm was not thought to shorten during loading because there was no change in the abdominal cross-sectional area. The diaphragm was not at a disadvantageous position of its length-tension relationship. Therefore, shortening of the inspiratory muscles may contribute to the decrease in PI,, to a lesser extent. Diaphragmatic blood flow is inhibited by its contraction, and an increase in blood flow occurs during its relaxation phase (2). Diaphragmatic blood flow increases when breathing occurs against expiratory resistance (24). On the other hand, positive pressure around the diaphragm during contraction is reported to disturb its blood flow (4). Diaphragmatic blood flow can be impeded if pressure applied to the compliant compartment, i.e., capillaries and veins, is large enough and the duration of the applied pressure is long enough. In the present study, the Pm during expiration was 19 and 24 cmH,O with R2 and R3 expiratory loading, respectively, and TE (TE/
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2638
EXPIRATORY
A
RATIO
H/L
100
100
50
50
a > 0 -I a CENTROID FREQUENCY c -z iL 100
*
0 *
50
FATIGUE
.B RECOVERY PERIOD
DURING EXP. LOADING H/L
ILI 3 I
MUSCLE
0
RATIO
meon*SE n=5 I
I
1
1
I
1
I
1
I
CENTROID FREQUENCY
loo 50
0 MIDDLE
INITIAL
END
c
LOADED BREATHING
1
5
10
15
TT > 0.75) was long enough. Therefore, it is probable that positive pressure around the diaphragm during prolonged expiration decreased diaphragmatic blood flow and thus 0, delivery. Inspiratory loading with R2 caused only a slight decrease in both PE,,, and PI,,, during recovery; expiratory loading, with the same resistance, decreased PE,, and PI,, to a greater extent. FRC, however, did not change during inspiratory loading, suggesting that the 2. Thoracoabduminal configuration during expiratory loading with R2
at FRC
Recovery Period,min Loading Rib cage 3rd ICS AP LT Area Xiphoid AP LT Area Abdomen AP LT Area
1
15
30
60
105,0_+1*1~ 100.8~0.7 100.3tl.O lOO.lt0.5 105.3*1.7* 100.9kl.2
101.Otl.l 99.9kO.7 100.9k1.6
102.3k1.4 99.4kl.O 101.2k1.5
99.8kO.9 99.5kO.7 99.3k1.4
105.5+1.0t 102.1~2.0 107.7a2.7t
99.020.9 100.6t2.7 99.5k1.9
99.4k1.4 101.4*1.1 100.7t1.2
98.6tl.7 100.4tl.l 99.0t1.9
100.6t2.0 101.6k1.9 102.1+0.8 -
100.3t1.9 lOl.lt1.9 101.2k2.3
100.5*1.3 lOO.lkO.6 100.6k1.7
98.5~0.9 101.1t0.8 99.4k1.4
97.7k1.7 100.6kO.5 98.2t1.5
98.8k2.9 101.5t0.8 98.7k2.6
Values (means k SE) are expressed as percentage of control value obtained during quiet tidal breathing; n = 5. R2, moderate resistance; ICS, intercostal space; AP, anteroposterior diameter; LT, lateral diameter; Area, (AP/2) X (LT/2) X ?r. Compared with control (by ANOVA):
*P < 0.05, t P < 0.005.
45
60
TIME AFTER LOADING (min)
FTG. 4. II/L ratio (top) and centroid frequency (bottom) of abdominal EMG during R2 expiratory during PE,, measurement in recovery period (B). Values are expressed as a percentage of initial part value at control PE,, measurement (B). Compared with control: tP < 0.01, $P < 0.005.
TABLE
30
loading of loading
(A) and (A) or
diaphragm was not at mechanical disadvantage during inspiratory loading. Although the TTI of the inspiratory muscle cannot be evaluated exactly because of the nonsquare Pm waveform and because of a noncontrolled TI/ TT, the TTI calculated using the time-integrated mean Pm value and the mean TI/TT value was ~0.2 in one-half of the subjects. This TTI value was close to the critical fatigue threshold of the diaphragm, according to Bellemare and Grassino (1). Therefore, the magnitude of R2 may not always be large enough to induce inspiratory muscle fatigue. On the other hand, the abdominal muscles are reported to be recruited during inspiratory loading to facilitate inspiration (15). A small decrease in PE max was observed just after inspiratory loading, but this was not significant statistically. This slight decrease hPE,, may be due to a central component, because it recovered soon. As can be deduced from the pressure-volume diagram of Rahn et al. (23), PE,,, is maximal at TLC and then decreases as the lung volume decreases; our present data show a similar relationship between pressure and lung volume. In the present study, the subjects could not maintain a resting level FRC during expiratory loading, despite a prolonged TE. Thus FRC increased as the expiratory resistance increased to allow the expiratory muscles to increase the expiratory force generated. Expiratory loading is known to change the ventilatory pattern by slowing the breathing frequency and increasing the tidal volume (10). During expiratory loading with Rl, R2, and R3, breathing frequency decreased by 55%, and the tidal volume increased by 60%. TE/TT increased with larger resistances. Thus the respiratory pattern
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EXPIRATORY
MUSCLE
adapts to an increase in the expiratory work of breathing by optimizing the pressure-volume relationships in breathing to allow expiratory muscles to generate greater forces. Furthermore, the increase in FRC during expiratory loading may take advantage of passive recoil of the respiratory system, reducing the increased work of the expiratory muscles caused by the external resistance. In summary, expiratory resistive loaded breathing induces muscle fatigue in both expiratory and inspiratory muscles. Also, as reported by previous authors (1, 9, 11, 14,22,26,27), inspiratory loaded breathing causes inspiratory muscle fatigue. Thus it is possible that, in obstructive pulmonary diseases, airway obstruction may contribute to fatigue of both inspiratory and expiratory muscles. The authors thank Dr. James P. Butler for helpful advice in preparing the manuscript. Address for reprint requests: S. Suzuki, First Dept. of Internal Meditine, Yokohama’ City University School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236, Japan. I
Received 27 September 1989; accepted in final form 6 February
1991.
GARRARD, C. S., AND D. J. LANE. The pattern of stimulated breathing in man during non-elastic expiratory loading. J. Physiol. Land 279: 17-29,1978. 11. GROSS, D., A. GRASSINO, W. R. D. Ross, AND P. T. MACKLEM. Electromyogram pattern of diaphragmatic fatigue. _ - J. Appl. Physiol. 46: l-7, i979. 12. KIM, M. J., W. S. DRUZ, J. DANON, W. MACHNACH, AND J. T. SHARP. Mechanics of the canine diaphragm. J. Appl. Physiol. 41: 369-382,1976. 13. KOGI, K., AND
T. HAKAMAD A. Slowing of Surface electromyogram and muscle strength in muscle fatigue. Rep. Inst. Sci. Labour Tokyo
60: 27-41,1962. 14. MACKLEM, P.
T., AND C. S. Roussos. Respiratory muscle fatigue: a cause of resniratorv failure? Clin. Sci. Mol. Med. 53: 419-422.1977. * 15. MARTIN, J. G., AN;) A. DE TROYER. The behaviour of the abdominal muscles during inspiratory mechanical loading. Respir. Physiol. 50: 63-73,1982. 16. MARTIN, J.
G., M. HABIB, AND L. A. ENGEL. Inspiratory muscle activity during induced hyperinflation. Respir. Physiol. 39: 303-
313,198O. 17. MCILORY, 18. 19.
F., AND A. GRASSINO. Effect of pressure and timing of on human diaphragm fatigue. J. Appl. Physiol. 53:
20.
F., D. WIGHT, C. M. LAVIGNE, AND A. GRASSINO. Effect of tension and timing of contraction on the blood flow of the diaphragm. J. Appl. Physiol. 54: 1597-1606,1983. 3, BLACK. L. F.. AND R. E. HYATT. Maximal respirator-v pressures: normal values and relationship to age and sex. Am. Rev. Respir. Dis. 99: 696-702,1969. 4. BUCHLER, B., S. MAGDER, H. KATSARDIS, Y. JAMMES, AND C. ROUSSOS. Effects of pleural pressure on diaphragmatic blood flow. J. Appl. Physiol. 58: 691-697, 1985. 5. BYRD. R. B., AND R. E. HYATT. Maximal respiratory pressures in chronic obst’ructive lung disease. Am. Rev. Respir. DE. 98: 848-856,
21.
contraction 1190-1195,1982. 2. BELLEMARE,
~
I
I
1968. 6. CAMPBELL, J. T. W. SHIELDS.
-
a
A., R. L. HUGHES, V. SAHGAL, J. FREDERIKSEN, AND Alternations in intercostal muscle morphology and in patients with obstructive lung disease. Am. Rev.
biochemistry Respir. Dis. 122: 679-686, 1980. 7. COTES, J. E. Lung Function; Assessment and Application in Medicine (4th ed.). Oxford, UK: Blackwell, 1979, p. 329-387. 8. EDWARDS, R. H. T. Physiological analysis of skeletal muscle weakness and fatigue. Clin. Sci. Mol. Med. 54: 463-470, 1978. 9. FITTING, J. W., T. D. BRADLEY, P. A. EASTON, M. J. LINCOLN, M, D. GOLDMAN, AND A. GRASSINO. Dissociation between diaphragmatic and rib cage muscle fatigue. J. Appl. Physiol. 64: 959-965, 1988.
2639
10.
REFERENCES 1, BELLEMARE,
FATIGUE
22.
23.
24.
25.
26.
27. 28.
M. B., AND R. V. CHRISTIE. The work of breathing in emphysema. Clin. Sci. Lond. 13: 147-154, 1954. MEAD, J. Functional significance of the area of apposition of diaphragm to rib cage. Am. Rev. Respir. Dis. 119: 31-32, 1979. MEAD, J., N. PETERSON, G. GRIMBY, AND J. MEAD. Pulmonary ventilation measured from body surface movements. Science Wash. DC 156: 1383-1384,1967. MIER, A., C. BROPHY, M. ESTENNE, J. MOXHAM, M. GREEN, AND A. DE TROYER. Action of abdominal muscles on rib cage - in humans. J. Appl. Physiol. 58: 1438-1443,1985. MILIC-EMILI, J., J. MEAD, J. M. TURNER, AND E. M. GLAUSER. Improved technique for estimating pleural pressure from esophageal balloons. J. Appl. Physiol. 19: 207-211, 1964. MOXHAM, J., R. H. T. EDWARDS, M. AUBIER, A. DE TROYER, G. FARKAS. P. T. MACKLEM, AND C. Roussos. Changes in EMG power spectrum (high-to-low ratio) with force fatigue in humans. J. Appl. Physiol. 53: 1094-1099, 1982. RAHN, H., A. B. OTIS, L. E. CHADWICK, AND W. 0. FENN. The pressure-volume diagram of the thorax and lung. Am. J. Physiol. 146: 161-178,1946. ROBERTSON, C.
H. JR., W. L. ESCHENBACHER, AND R. L. JOHNSON, JR. Respiratory muscle blood flow distribution during expiratory resistance. J. C&n. Invest. 60: 473-480, 1977. ROCHESTER, D. F., N. M. BRAUN, AND N. S. ARORA. Respiratory muscle strength in chronic obstructive pulmonary disease. Am. Rev. Respir. Dis. 119: 151-154, 1979. ROUSSOS, C. S., M. FIXLEY, D. GROSS, AND P. T. MACKLEM. Fatigue of inspiratory muscles and their synergic behavior. J. Appl. Physiol. 46: 897-904,1979. R&SSOS, C. S., AND P. T. MACKLEM. Diaphragmatic fatigue in man. J. ADDS. Physiol. 43: 189-197, 1977. SIECK, G.?., A. %IAZAR, AND M. J.‘BELMAN. Changes in diaphragmatic EMG spectra during hyperpneic loads. Respir. Physiol. 61: 137-152,1985.
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