Effect of respiratory muscle fatigue on subsequent exercise performance M. JEFFERY MADOR AND FREDERIC A. ACEVEDO Division of Pulmonary Medicine, State University of New York at Buffalo, Veterans Administration Medical Center, Buffalo, New York 14215 MADOR, M. JEFFERY,ANDFREDERIC
A. AcEvEDo.E~~~~~o~ J. Appl. Physiol. 70(5): 2059-2065, 1991.-The purpose of this study was to determine whether induction of inspiratory muscle fatigue might impair subsequentexerciseperformance. Ten healthy subjectscycled to volitional exhaustion at 90%of their maximal capacity. Oxygen consumption, breathing pattern, and a visual analogue scale for respiratory effort were measured. Exercise was performed on three separate occasions, onceimmediately after induction of fatigue, whereasthe other two episodesserved as controls. Fatigue wasachieved by having the subjectsbreathe against an inspiratory threshold load while generating 80% of their predetermined maximal mouth pressureuntil they could no longer reach the target pressure. After induction of fatigue, exercisetime wasreducedcompared with control, 238 t 69 vs. 311 k 96 (SD) s (P < 0.001). During the last minute of exercise,oxygen consumptionand heart rate were lower after induction of fatigue than during control, 2,234t 472vs. 2,533t 548ml/min (P < 0.002)and 167t 15vs. 177t 12 beats/min (P < 0.002). At exercise isotime, minutes ventilation and the visual analoguescalefor respiratory effort were larger after induction of fatigue than during control. In addition, at exercise isotime, relative tachypnea was observed after induction of fatigue. We concludethat induction of inspiratory muscle fatigue can impair subsequentperformance of high-intensity exerciseand alter the pattern of breathing during such exercise. respiratory
muscle fatigue on subsequent exercise performance.
oxygen consumption; visual analoguescalefor respiratory effort; inspiratory threshold load
IT HAS BEEN SHOWNthat the inspiratory muscles if subjected to high loads for a sufficient period of time will eventually fatigue (25). Fatigue of the inspiratory muscles may be an important contributor to hypercapnic ventilatory failure (15). In the laboratory setting, inspiratory muscle fatigue can be induced acutely in healthy human subjects. The consequences of this form of fatigue on subsequent ventilatory performance during constant-load exercise have not been assessed. We recently examined the pattern of breathing during incremental leg exercise after induction of fatigue compared with control (1). We observed that 4 of the 10 subjects studied were unable to complete the exercise protocol after induction of fatigue, whereas all subjects were able to complete the protocol in the absence of fatigue. This suggested that induction of inspiratory muscle fatigue might impair subsequent performance of high-intensity exercise. To test this hypothesis, we studied healthy subjects 0161-7567191
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during high-intensity constant-work-load leg exercise (90% of maximal capacity) to exhaustion in the absence of fatigue (control) and after the induction of inspiratory muscle fatigue. A shorter exercise duration after induction of fatigue compared with control would support our hypothesis that induction of fatigue can adversely affect subsequent exercise performance. In addition, we examined the breathing pattern during exercise because alterations in breathing pattern, in particular, rapid shallow breathing, have been observed in the immediate recovery period after induction of fatigue in several animal preparations (21, 23) and also under certain circumstances in humans (1, 10, 12). METHODS Subjects. Ten healthy subjects, seven men and three women, volunteered for this study. Their age was 29.3 t 5.0 (SE) yr (range 22-36 yr), weight 70 t 10 kg (range 57-89 kg), and height 173 t 10 cm (range 160-188 cm). All subjects had preliminary spirometry (Ohio spirometer) performed with measurement of the forced expiratory volume in 1 s (FE&), forced vital capacity (FVC), FEV,/FVC, and 12-s maximum voluntary ventilation (MVV). The FVC was 4.59 t 0.98 liters (percent predicted 101 t 8%), FEV, 3.74 t 0.78 liters (percent predicted 97 t 8%), and FEV,/FVC 82 t 5%. The MVV was 165 t 46 l/min (percent predicted 108 t 14%). The study was approved by the appropriate Institutional Review Boards, and informed consent was obtained from all subjects. Apparatus. The subjects breathed through a two-way nonrebreathing valve of low resistance and dead space (model 2600, Hans Rudolph). Inspiratory flow was measured with a pneumotachograph (model 3813, Hans Rudolph) and a k5 cmH,O differential pressure transducer (Validyne MP-45). Tidal volume (VT) was obtained by integration of the flow signal. Expired gas was passed through a mixing chamber and analyzed for 0, and CO, by a paramagnetic 0, analyzer (ADC) and an infrared CO, analyzer (ADC), respectively. The heart rate (HR) was determined from the electrocardiograph. The electrical signals from the recording amplifiers were connected to a microprocessor that performed analog-to-digital conversions and calculated average values of inspired ventilation (VI), VT, respiratory frequency (f), 0, uptake (VO,), CO, production (VCOJ, and HR every 30 s. The values were continu-
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ously printed and simultaneously stored on disk. The inspiratory flow signal was recorded on a strip chart recorder (Gould), and inspiratory time (TI), expiratory time, and fractional inspiratory time (TI/TT) were measured by hand from this tracing. Expired CO, was sampled at the mouthpiece and analyzed by a second infrared CO, analyzer (Beckman, Medical Gas Analyzer, LB-2) andwas recorded breath-by-breath on the strip chart recorder. End-tidal CO, (FETED,)I was measured from this tracing. All equipment was calibrated before each exercise test. 0, and CO, analyzers were calibrated with two test gases of known composition. The pneumotachograph was calibrated with a volume calibration syringe. Inspiratory resistance of the exercise circuit was 1.7 cmH,O 1-l. s at a flow of 60 l/min and 2.2 cmH,O 1-l. s at a flow of 120 l/min. Expiratory resistance was 0.7 cmH,O?* s at flows of 60 and 120 l/min. MVV measured directly on the exercise circuit in five of the subjects was 106.3 t 4.4% of spirometer MVV. The sensation of respiratory effort was assessed with a visual analog scale (VAS) (2) consisting of a vertical straight line 100 mm in length labeled “breathing very very light” at the bottom and “breathing very very hard” at the top. Subjects were instructed to point to a spot on the line indicating the intensity of their sensation of respiratory effort at that particular point in time (an attendant made the actual mark on the line). VAS measurements were obtained every minute during exercise. The subjects were specifically instructed to scale their “effort to breathe” and to disregard any other sensations associated with whole-body exercise. Exercise testing. Subjects were studied on four separate occasions. On the 1st day a preliminary incremental exercise test was performed on an electronically braked cycle ergometer (Rodby Electronik) to determine the maximal work capacity (Wmax) for each subject. After 1 min of unloaded cycling, the work load was increased by 25 W every minute until the subject could no longer continue. The last work load for which the subject was able to complete the full minute of cycling was designated Wmax. On the 2nd, 3rd, and 4th experimental days, the subject exercised on the same cycle ergometer. Th .e subjects were allowed 2-3 min to acclimatize to the breathing circuit and then exercised for 2 min at 50 W (warm-up period) before initiating exercise at 90% of Wmax. The subjects exercised at 90% of Wmax until they were no longer able to maintain the pedaling frequency above 40 rpm. On day 3 t exercise was performed after induction of inspiratory muscle fatigue, whereas exercise alone was performed on days 2 and 4 (controls). All exercise tests were separated by 22 days. Znspiratory loading. The subject’s maximal mouth pressure (Pm,,,) was measured with a differential pressure transducer (Validyne t350 cmH,O) while.performing a maximum inspiratory effort against an occluded airway ne ar residual volume (7). The pressure transducer was calibrated with a me rcury manometer before each study. To prevent glottic cl0 sure, a small le ak was produced by i nsertion of an 18 -gauge needle in the mouthpiece. Pm maxmaneuvers were repeated unti 1 three reproducible measurements that were sustained for at least 1 s were recorded. The highest value obtained was l
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used for analysis. After completion of the Pmmax maneuvers, the subjects were instructed to breathe against an inspiratory threshold load. Threshold loading was performed using the technique of Nickerson and Keens (20). All subjects practiced on the threshold load for one or more sessions before initiation of the experimental protocol. With this technique, initiation of airflow requires development of a level of pressure sufficient to lift a plunger that in the fully dependent position occludes the orifice of an otherwise sealed cylinder. Weights were added to the plunger so that the subjects were required to generate 80% of their Pmmax to initiate airflow. Expiration was unloaded, and the subjects were allowed to choose their own breathing pattern. TI/TT adopted during threshold loading was 0.56 t 0.08 (range 0.50-0.71). The target pressure was maintained for 280% of the inspiratory effort in every subject until the final minute of threshold loading (when task failure started to show). The endurance time was calculated as the time from the start of the run until the subject was no longer able to generate the target pressure in a square-wave fashion for five consecutive breaths. In this experiment, endurance time was 15.3 t 7.3 min. When the subject was unable to generate the target pressure for five consecutive inspiratory efforts, all the inspiratory muscles including the diaphragm were considered to be fatigued. Data analysis. To account for the variation in duration of exercise between subjects and between trials, the following analysis was performed. First, the last minute of exercise during the control trials was compared with the last minute of exercise after the induction of fatigue. Second, the last minute of exercise during the shortest exercise trial was compared with the equivalent time period during the other two exercise trials (isotime comparison). Comparisons were made by one-way analysis of variance with a repeated measures design. If the overall analysis of variance was significant, the two control runs were compared with each other to determine whether the experimental protocol itself affected the response to exercise due to either a training or learning effect. Because there were no significant differences between the control trials, the average of the two control trials was then compared with the fatigue trial. P = 0.025 was considered significant [Bonferroni correction for multiple (two) comparisons]. The results are expressed as means t SD unless otherwise stated. RESULTS
During the preliminary incremental exercise test, Wmax was 215 t 34 W and maximal 0, uptake (vo2 ,,,) was 2.54 t 0.45 l/min (36.6 t 5.4 ml min. kg-‘). No significant differences were observed in any of the measured parameters between the two control trials. The induction of inspiratory muscle fatigue produced a fall in Pm,,, in every subject from a baseline value of 138 t 33 to 110 t 31 cmH,O (P < 0.005) (79.7% of baseline value). Induction of inspiratory muscle fatigue also caused a reduction in exercise duration, 238 t 69 s, compared with both control periods, 302 t 87 (control 1) and 319 t 108 (control 2) (P < 0.001) (Fig. 1). This represents a 23% reduction in exercise duration. l
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TABLE 2. Isotime comparison of cardiorespiratory parameters during exercise after induction of fatigue compared with control
1
500
Control
‘0‘ VO,, ml/min VI, l/min VT, liters
f, breaths/min TI, s TE, s TI/TT VT/TI, l/s VAS, mm FETCO,, %
100 A
I
Control FIG.
1. Exercise duration of fatigue. Exercise of fatigue.
1
I
Post
Control 2
Fatigue
I induction induction
for each subject during control and after duration was significantly reduced after
1. Cardiorespiratory parameters during last minute of exerise after induction of fatigue compared with control TABLE
Control
HR,
beats/min
VI, l/min
VAS, mm FETCO,, 5%
2,601&43 3,028-t509 174t14 91.7k16.9 82+25 5.OkO.6
1
Control
2,473&518 3,052-+623 180&B 92.4k21.3 85218 5.2-t0.5
2
2,388&563 78.1k18.4 2.63kO.77 30.8k6.5 0.91kO.22 0.93kO.21 0.49+0.05 2.80k0.68 73k24 5.4kO.5
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Control
Fatigue
2
2,336&447 78.3k 17.5 2.7OkO.84 30.7k7.4 0.95kO.27 1.03kO.34 0.49kO.05 2.78kO.70 69k17 5.620.7
2,234+472 87.2+17.9* 2.5OkO.81 36.8+8.5* 0.78&O. 18 0.82k0.217 0.49-+0.04 3.13+0.75t 83+26$ 5.1kO.3
Values are means + SD of 10 subjs. f, respiratory frequency; TI, inspiratory time; TE, expiratory time; TI/TT, fractional inspiratory time; VT/TI, mean inspiratory flow; see Table 1 footnote for definition of other abbreviations. Significant difference from average of control 1 and 2 values: * P < 0.001, t P < 0.01, $ P < 0.025.
The last minute of exercise after induction of fatigue was compared with the last minute of exercise during the control trials (Table 1). VO, was significantly less after induction of fatigue compared with control (Table 1) (P < 0.002). Similarly, VCO, and HR were both lower after induction of fatigue compared with control (P < 0.002 for both comparisons; Table 1). The respiratory quotient and FET,,, were not significantly different after induction of fatigue compared with control. There were also no significant differences in any of the breathing pattern components including VI after induction of fatigue. The VAS for respiratory effort was also similar after induction of fatigue compared with control (Table 1). Isotime comparisons yielded quite different results (Table 2). VO, was similar after induction of fatigue compared with control (Table 2, Fig. 2). Similarly, there were no significant differences in VCO, or HR after induction of fatigue. This indicates that the rate of increase in these metabolic parameters during exercise was similar after induction of fatigue compared with control. Thus the lower Vo2, which we observed after induction of fatigue, was solely due to the shorter exercise duration. Isotime VI was significantly greater after induction of
VO,, ml/min VCO,, ml/min
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Fatigue 2,234+472* 2,824+538* 167k15* 87.4+18.1 83_+26 5.1kO.3
Values are means + SD of !O subjs. %Jo2, 0, consumption; %o,, CO, production; HR, heart rate; VI, minute ventilation; VAS, visual analogue scale for respiratory effort; FET,,,, end-tidal COz. * Significant difference from average of controZ I and 2 values (P < 0.002).
fatigue compared with control (P < 0.002) (Table 2). FET,,, tended to be lower after induction of fatigue compared with control (P < 0.09). The increase in VI was due to an increase in f after induction of fatigue (P < 0.0001) (Table 2). VT, in fact, tended to be slightly lower after induction of fatigue compared with control (P < 0.04). The increase in f was due to a decrease in both expiratory time (P < 0.006) and TI after induction of fatigue, although the change in TI did not reach statistical significance. TI/TT remained unchanged after induction of fatigue. Mean inspiratory flow (VT/TI), a crude index of respiratory drive, increased after induction of fatigue compared with control (P < 0.003) (Table 2). VAS scores were reproducible at end exercise and exercise isotime (coefficient of variation for the 2 control trials was 4.1 t 2.2% at end exercise and 12.0 t 3.1% at exercise isotime). The isotime VAS for respiratory effort increased after induction of fatigue (Table 2) (P < 0.025). The increase in VAS was proportional to the increase in VI so that the slope and position of the VAS-VI relationship was not significantly altered by induction of fatigue. The slope of the VAS-VI relationship was 1.30 t 0.31 during control compared with 1.22 t 0.36 mm 1-l. min after induction of fatigue (P = NS). The VAS at a VI of 50.0 l/min was 40.3 t 11.1 during control compared with 39.4 t 19.5 mm after induction of fatigue (P = NS), indicating that the position of the VAS/VI relationship was not altered by the induction of fatigue. The time course of changes during exercise in Vo2, f, VT, and VI after induction of fatigue compared with control are shown in Fig. 2. In Fig. 2, the beginning, middle, and final minutes of the fatigue exercise trial are compared with the same time period during the control trials. At any given isotime, 00, was similar after induction of fatigue compared with control. At the beginning and middle of the fatigue exercise trial, VT was similar to isotime control VT. At the end of the fatigue exercise trial, VT tended to be smaller than isotime control VT (P < O.O4), although this difference did not reach statistical significance. The time course of changes in the VAS for respiratory effort is shown in Fig. 3. At the beginning of the exercise trials, the VAS scores were not significantly l
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-
25
B
o-0Control
F.- 80 \E G 60 40 IO C
I’
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FIG. 2. 0, consumption (vo2), minute ventilation #I), tidal volume (VT), and respiratory frequency (f) during the 1st min (B), the middle minute (M), and the final minute (E) of exercise after induction of fatigue (V) and during the same time period (isotime) in the absence of fatigue (control, 0). Values are means f SE of 10 subjs. Control curve represents average of 2 control trials. *Significant difference from average of 2 control trials (P < 0.01). At any given time during exercise, VI and f after induction of fatigue were greater than control values.
different after induction of fatigue compared with control. At the middle and end of the fatigue exercise trial, the VAS score for respiratory effort was higher than the isotime control VAS score.
We made considerable efforts to exclude motivation as a factor by choosing only highly motivated subjects and by constantly encouraging the subjects during the loaded breathing runs. Studies employing a similar protocol and definition of fatigue but with measurement of DISCUSSION transdiaphragmatic pressure generation in response to The major findings in this study were as follows: 1) phrenic nerve stimulation have invariably shown the deacute induction of inspiratory muscle fatigue resulted in velopment of peripheral low-frequency fatigue, as dema decrease in exercise duration and 2) after induction of onstrated by a reduction in transdiaphragmatic presfatigue, relative tachypnea was observed during high-insure at the low physiological frequencies of stimulation tensity exercise. (4, 5, l&19). Critique of methods. The question arises as to whether Subsequent to this experiment, we have examined the our subjects developed inspiratory muscle fatigue, be- tension-time index of the diaphragm and of the rib cage cause our study design did not include an independent in subjects undergoing loaded breathing trials identical measure of fatigue. We employed a method similar to to those performed in this study. The tension-time inthat of Roussos et al. (25) and others (1,4,5,12,18,19) dex of the diaphragm was 0.28 t 0.05 and exceeded the for the induction of inspiratory muscle fatigue. In these fatigue threshold for the diaphragm of 0.15-0.18 (6) in experiments , it was fou nd that a mouth pressure exceed- every trial (29 trials in 7 subjects). Similarly, the tening 60% of maxim urn could not be sustained indefision-time index of the rib cage was 0.38 t 0.06 and exnitely. Extrapol ating from the definition of. skeletal ceeded the fatigue threshold for the rib cage of 0.26-0.30 muscle fatigue, i. e., the inability to maintain a predeter(11) in every subject (M. J. Mador, unpublished obsermined load, Roussos an d Ma .cklem considered that all vations). On the basis of the above points, we are confithe ins piratory must les were fatigued when the subject dent that fatigue of the inspiratory muscles was could no longer achieve the target mouth pressure by achieved in our subjects. any means. The inability to generate the required presExercise Limitation. After induction of inspiratory mussure could be due to motivational factors, peripheral cle fatigue, the ability to perform high-intensity exercise muscle contractile fatigue (peripheral fatigue), or a re- was impaired. Exercise duration fell by 23% after induction of fatigue compared with control (Fig. 1). This reduction in central neural motor drive (central fatigue). Downloaded from www.physiology.org/journal/jappl by ${individualUser.givenNames} ${individualUser.surname} (163.015.154.053) on August 7, 2018. Copyright © 1991 American Physiological Society. All rights reserved.
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FIG. 3. Visual analogue scale for respiratory effort (VAS) during the 1st minute (B), the middle minute (M), and the final minute (E) of exercise after induction of fatigue (0) and during the same time period (isotime) in the absence of fatigue (control, 0). Values are means + SE of 10 subjs. Control curve represents average of 2 control trials. “Significant difference from average of 2 control trials (P < 0.025). At the middle and end of exercise after induction of fatigue, VAS score for respiratory effort was higher than isotime control VAS score.
duction in exercise duration was associated with a lower that. inspiratory muscle fatigue can 2 max) indicating prevent attainment of V02max during exercise. It would be of interest to see if a similar or even greater decrease in exercise duration occurs after induction of fatigue by voluntary hyperpnea, an activity that more closely approximates the demands placed on the ventilatory pump by exercise. The difference in exercise tolerance could not have been due to a learning or training effect related to the exercise protocol because there was no significant difference between the control trials performed several days before and several days after the fatigue run. It could be argued that, because of the exhausting nature of threshold loaded breathing to fatigue, our subjects did not put forth as good an effort after induction of fatigue compared with control. However, at end exercise, VI and VT/ TI were similar after induction of fatigue compared with control (Table 1), implying that the degree of respiratory effort was at least equal if not greater after induction of fatigue (because induction of fatigue was associated with mild respiratory muscle weakness). Furthermore, the respiratory quotient at end exercise was similar after induction of fatigue (1.29 t 0.18) compared with control (1.21 t O.l3), suggesting that skeletal muscle effort was not substantially different under the two circumstances. There are a number of additional potential mechanisms by which induction of inspiratory muscle fatigue might impair subsequent exercise performance. High-intensity exercise might itself be fatiguing to the inspiratory muscles, as has been suggested by other investigators (8, 14). If this were the case, one might expect greater alterations in the function of muscles that were already fatigued compared with those in the fresh state. This greater muscle dysfunction could in turn limit the ventilatory response to exercise, resulting in premature termination of the exercise trial. However, in this study, the ventilatory response to exercise was actually enhanced after induction of fatigue. Thus the degree of vo
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muscle dysfunction induced by inspiratory muscle fatigue in this study was not sufficient to produce a ventilatory limitation to exercise. VI increased markedly during exercise. This increase in VI is achieved by an increase in respiratory muscle work. As the respiratory muscles work harder, they consume more 0,. Bye and colleagues (9) have speculated that during heavy exercise, 0, consumption by the respiratory muscles may reduce the amount available to the exercising skeletal muscle, thus limiting exercise performance. However, recent estimates of the 0, cost of ventilation suggest that at a ventilation of -100 l/min the 0, cost of ventilation is between 1.5 and 2.5 ml/l of ventilation (3). Because at exercise isotime, v, was -9 l/min greater after induction of fatigue than during control, the cost of this added ventilation would be 23 ml/min, a trivial amount that is unlikely to have influenced exercise endurance. It could be argued that induction of fatigue by producing mild muscle weakness may have reduced inspiratory muscle efficiency. Induction of fatigue may also have depleted the inspiratory muscles of their nutrient stores, increasing their requirement for delivered 0,. These factors could increase the 0, cost of ventilation. However, if the 0, cost of ventilation was truly increased after induction of fatigue, VO, during submaximal exercise should have been larger after induction of fatigue than during control. This was not the case (Fig. 2), indicating that this mechanism is unlikely to have played a major role in our study. For any given level of inspiratory pressure, the sensation of respiratory effort is greater after induction of fatigue than during control (13). In this study, the isotime VAS for respiratory effort was larger after induction of fatigue than during control. Thus our subjects could have stopped exercise prematurely after induction of fatigue because of a greater sense of respiratory effort. In a previous study by Martin and colleagues (17) in which subjects performed a highly rigorous but probably nonfatiguing task (subjects hyperventilated at their volitional maximum for 150 min), subsequent incremental treadmill exercise was terminated prematurely compared with control exercise. This decrease in exercise performance appeared to be due to an increase in unpleasant respiratory sensations, although sensation was not objectively quantified. Similarly, the subjects of Bye and colleagues (8), who performed high-intensity exercise (80% of Wmax) until volitional exhaustion, complained predominantly of dyspnea at end exercise. In our study, at exercise isotime the VAS for respiratory effort was indeed larger after induction of fatigue than during control. It is of interest that our subjects reported that they stopped exercise predominantly because of leg fatigue rather than dyspnea. However, at end exercise the VAS scores for respiratory effort were quite high, exceeding 80 mm in nine of the subjects and 90 mm in six of the subjects. It is likely that both leg and respiratory sensations contributed to exercise termination in our subjects. Therefore we believe that an increase in the sense of respiratory effort during exercise is the most likely explanation for our subject’s decreased exercise tolerance after induction of inspiratory muscle fatigue. In turn, this increase in the sense of respiratory effort appears to be largely because
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of the enhanced ventilatory response to exercise induced by inspiratory muscle fatigue. Respiratory motor output and respiratory sensation. At exercise isotime, VI and VT/TI were greater after induction of fatigue than during control (Table 2). Increases in VI and VT/TI after induction of fatigue indicate an increase in central respiratory drive, albeit this increase may be underestimated. A portion of this increase in drive was presumably compensatory in nature, maintaining VI in the presence of mild muscle weakness (P m maxfell by 20% after induction of fatigue). However, at exercise isotime, VI was larger after induction of fatigue than during control, indicating an additional stimulus to ventilation. We have obtained similar results in a previous study in which we examined the effects of inspiratory muscle fatigue on the breathing pattern during incremental exercise (1). Stimulation of thin fiber afferents within the diaphragm results in an increase in diaphragmatic electrical activity (22), and we speculated that these fibers may have been responsible for the increase in respiratory drive that we observed, as has previously been suggested (23). At exercise isotime, the VAS for respiratory effort was greater after induction of fatigue than during control (Table 2). As described above, both VI and VT/TI were increased after induction of fatigue, indicating an increase in central motor drive. Our subjects were able to perceive this increase in respiratory effort as indicated by the increase in VAS measurements after induction of fatigue. In an attempt to determine whether fatigue altered the perception of respiratory effort independent of alterations in central motor drive, we examined the relationship between the VAS for respiratory effort and VI during control and after induction of fatigue. Neither the slope nor position of the VAS-VI relationship was altered by induction of fatigue. Therefore the increase in VAS measurements after induction of fatigue in this study may be explained by the increase in central respiratory drive and no additional mechanisms need be invoked. Pattern of breathing. At exercise isotime, a pattern of rapid shallow breathing was observed after induction of fatigue compared with control. A similar pattern of breathing has been observed after induction of fatigue in both an anesthetized (23) and awake animal preparation (21). Rapid shallow breathing has also been observed after induction of fatigue in human subjects (10, 12). However, we were unable to elicit rapid shallow breathing after induction of fatigue in healthy human subjects during resting unstimulated breathing (1, 16). In contrast, when we increased VI by incremental leg exercise, a pattern of rapid, albeit not shallow, breathing became apparent at the higher work loads (1). During resting unstimulated breathing, the ventilatory pump had considerable reserve even after the induction of f@igue. In contrast, during high-intensity exercise, the ventilatory pump is stressed to a considerably greater degree, and the changes in breathing pattern consequent to inspiratory muscle fatigue may then become more apparent. In this study, we also observed rapid and a tendency towards shallow breathing during high-intensity exercise after induction of fatigue. Interestingly, tachypnea was observed even during the 1st min of exercise after induc-
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tion of fatigue when VI was only 35.97 -t 6.20 l/min (Fig. 2). This VI is lower than that required to produce tachypnea in our previous study (1). However, because of the nature of the studies, the time elapsed from induction of fatigue to exercise at high work loads was much shorter in this study (5 min vs. 12 min), and this likely accounts for the greater ease with which tachypnea was elicited. The mechanism by which inspiratory muscle fatigue elicits rapid shallow breathing has not been fully delineated. Potential mechanisms have been discussed previously (1, 12, 21, 23, 24). In summary, induction of inspiratory muscle fatigue impaired subsequent performance of high-intensity constant-work-load leg exercise. In addition, induction of inspiratory muscle fatigue increased the ventilatory response to exercise and altered the pattern of breathing, producing tachypnea and increasing the sense of respiratory effort (VAS) for a given exercise isotime. We suggest that the reduction in exercise performance after induction of fatigue may be due to an increase in the sensation of respiratory effort during exercise consequent to the enhanced ventilatory response to exercise induced by inspiratory muscle fatigue. The authors thank Diane Poch for preparation of the manuscript, John Jankowski for technical assistance, and Dr. M. J. Tobin for careful review of the manuscript. This study was supported by grants from the American Lung Association of New York and American Heart Association of New York, an institutional grant from the State University of New York at Buffalo, and Veterans Administration Medical Research Funds. Address for reprint requests: M. J. Mador, Pulmonary Div., Dept. of Medicine, School of Medicine, Veterans Administration Medical Center, 3495 Bailey Ave., Buffalo, NY 14215. Received 30 March 1990; accepted in final form 19 December 1990. REFERENCES
F. A., AND M. J. MADOR. The effect of respiratory muscle fatigue on breathing pattern during incremental exercise (Abstract). Am. Rev. Respir. Dis. 139: A604, 1989. ADAMS, L., N. CHRONOS, R. LANE, AND A. Guz. The measurement of breathlessness induced in normal subjects: validity of two scaling techniques. CZin. Sci. Lond. 69: 7-16, 1985. ANHOLM, J. D., R. L. JOHNSON, AND M. RAMANATHAN. Changes in cardiac output during sustained maximal ventilation in humans. J. Appl. Physiol. 63: 181-187, 1987. AUBIER, M., G. FARKAS, A. DE TROYER, R. MOZES, AND C. RousSOS. Detection of diaphragmatic fatigue in man by phrenic stimulation. J. Appl. Physiol. 50: 538-544, 1981. AUBIER, M., D. MURCIANO, Y. LECOCGUIC, N. VIIRES, AND R. PARIENTE. Bilateral phrenic stimulation: a simple technique to assess diaphragmatic fatigue in humans. J. Appl. Physiol. 58: 58-64, 1985. BELLEMARE, F., AND A. GRASSINO. Effect of pressure and timing of contraction on human diaphragm fatigue. J. Appl. PhysioZ. 53:
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9. 10.
11.
R. E. HYATT. Maximal respiratory pressures: normal values and relationship to age and sex. Am. Rev. Respir. Dis. 99: 696-701, 1969. BYE, P. T. P., S. A. ESAU, K. R. WALLEY, P. T. MACKLEM, AND R. L. PARDY. Ventilatory muscles during exercise in air and oxygen in normal men. J. Appl. Physiol. 56: 464-471, 1984. BYE, P. T. P., G. A. FARKAS, AND C. Roussos. Respiratory factors limiting exercise. Annu. Rev. Physiol. 45: 439-451, 1983. COHEN, C. A., G. ZAGELBAUM, D. GROSS, C. ROUSSOS, AND P. T. MACKLEM. Clinical manifestations of inspiratory muscle fatigue. Am. J. Med. 73: 308-316, 1982. FITTING, J. W., T. D. BRADLEY, P. A. EASTON, M. J. LINCOLN, M. D. GOLDMAN, AND A. GRASSINO. Dissociation between diaphrag-
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matic and rib cage muscle fatigue. J. Appl. Physiol. 64: 959-965, 1988. 12. GALLAGHER,
C. G., V. IM HOF, AND M. YOUNES. Effect of inspiratory muscle fatigue on breathing pattern. J. Appl. Physiol. 59:
1152-1158, 13. GANDEVIA,
14. 15. 16.
17. 18.
1985.
S. C., K. J. KILLIAN, AND E. J. M. CAMPBELL. The effect of respiratory muscle fatigue on respiratory sensations. Clin. Sci. Lond. 60: 463-466,198l. LOKE, J., D. A. MAHLER, AND J. A. VIRGULTO. Respiratory muscle fatigue after marathon running. J. Appl. Physiol. 52: 821-824,1982. MACKLEM, P. T., AND C. Roussos. Respiratory muscle fatigue: a cause of respiratory failure. Clin. Sci. Lond. 53: 419-422, 1977. MADOR, M. J., S. M. GUENTHER, AND M. J. TOBIN. The effect of respiratory muscle fatigue on breathing pattern and ventilatory response to CO, (Abstract). Am. Reu. Respir. Dis. 135: A296, 1987. MARTIN, B., M. HEINTZELMEN, AND H.-I. CHEN. Exercise performance after ventilatory work. J. Appl. Physiol. 52: 1581-1585,1982. 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. PhysioZ. 53: 1094-1099, 1982.
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J., A. J. R. MORRIS, S. G. SPIRO, R. H. T. EDWARDS, AND Contractile properties and fatigue of the diaphragm in man. Thorax 36: 164-168, 1981. 20. NICKERSON, B. G., AND T. G. KEENS. Measuring ventilatory muscle endurance in humans as sustainable inspiratory pressure. J. Appl. Physiol. 52: 768-772, 1982. 21. OLIVEN, A., S. LOHDA, M. E. ADAMS, B. SIMHAI, AND S. G. KELSEN. Effect of fatiguing resistive loads on the level and pattern of respiratory activity in awake goats. Respir. Physiol. 73: 311-324, 19. MOXHAM, M. GREEN.
1988. 22. REWLETTE,
W. R., L. A. JEWELL, AND D. T. FRAZIER. Effect of diaphragm small-fiber afferent stimulation on ventilation in dogs. J. Appl. Physiol. 65: 2097-2106, 1988. 23. ROAD, J., R. VAHI, P. DEL RIO, AND A. GFWSINO. In vivo contractile properties of fatigued diaphragm. J. Appl. Physiol. 63: 471-478, 1987. 24. ROUSSOS,
C. Ventilatory muscle fatigue governs breathing frequency. Bull. Eur. Physiopathol. Respir. 20: 445-451, 1984. 25. ROUSSOS,C., M. FIXLEY, D. GROSS, AND P. T. MACKLEM. Fatigue of inspiratory muscles and their synergic behavior. J. Appl. Physiol. 46: 897-904,
1979.
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A. AcEvEDo.E~~~~~o~ J. Appl. Physiol. 70(5): 2059-2065, 1991.-The purpose of this study was to determine whether induction of inspiratory muscle fatigue might impair subsequentexerciseperformance. Ten healthy subjectscycled to volitional exhaustion at 90%of their maximal capacity. Oxygen consumption, breathing pattern, and a visual analogue scale for respiratory effort were measured. Exercise was performed on three separate occasions, onceimmediately after induction of fatigue, whereasthe other two episodesserved as controls. Fatigue wasachieved by having the subjectsbreathe against an inspiratory threshold load while generating 80% of their predetermined maximal mouth pressureuntil they could no longer reach the target pressure. After induction of fatigue, exercisetime wasreducedcompared with control, 238 t 69 vs. 311 k 96 (SD) s (P < 0.001). During the last minute of exercise,oxygen consumptionand heart rate were lower after induction of fatigue than during control, 2,234t 472vs. 2,533t 548ml/min (P < 0.002)and 167t 15vs. 177t 12 beats/min (P < 0.002). At exercise isotime, minutes ventilation and the visual analoguescalefor respiratory effort were larger after induction of fatigue than during control. In addition, at exercise isotime, relative tachypnea was observed after induction of fatigue. We concludethat induction of inspiratory muscle fatigue can impair subsequentperformance of high-intensity exerciseand alter the pattern of breathing during such exercise. respiratory
muscle fatigue on subsequent exercise performance.
oxygen consumption; visual analoguescalefor respiratory effort; inspiratory threshold load
IT HAS BEEN SHOWNthat the inspiratory muscles if subjected to high loads for a sufficient period of time will eventually fatigue (25). Fatigue of the inspiratory muscles may be an important contributor to hypercapnic ventilatory failure (15). In the laboratory setting, inspiratory muscle fatigue can be induced acutely in healthy human subjects. The consequences of this form of fatigue on subsequent ventilatory performance during constant-load exercise have not been assessed. We recently examined the pattern of breathing during incremental leg exercise after induction of fatigue compared with control (1). We observed that 4 of the 10 subjects studied were unable to complete the exercise protocol after induction of fatigue, whereas all subjects were able to complete the protocol in the absence of fatigue. This suggested that induction of inspiratory muscle fatigue might impair subsequent performance of high-intensity exercise. To test this hypothesis, we studied healthy subjects 0161-7567191
$1.50
and
during high-intensity constant-work-load leg exercise (90% of maximal capacity) to exhaustion in the absence of fatigue (control) and after the induction of inspiratory muscle fatigue. A shorter exercise duration after induction of fatigue compared with control would support our hypothesis that induction of fatigue can adversely affect subsequent exercise performance. In addition, we examined the breathing pattern during exercise because alterations in breathing pattern, in particular, rapid shallow breathing, have been observed in the immediate recovery period after induction of fatigue in several animal preparations (21, 23) and also under certain circumstances in humans (1, 10, 12). METHODS Subjects. Ten healthy subjects, seven men and three women, volunteered for this study. Their age was 29.3 t 5.0 (SE) yr (range 22-36 yr), weight 70 t 10 kg (range 57-89 kg), and height 173 t 10 cm (range 160-188 cm). All subjects had preliminary spirometry (Ohio spirometer) performed with measurement of the forced expiratory volume in 1 s (FE&), forced vital capacity (FVC), FEV,/FVC, and 12-s maximum voluntary ventilation (MVV). The FVC was 4.59 t 0.98 liters (percent predicted 101 t 8%), FEV, 3.74 t 0.78 liters (percent predicted 97 t 8%), and FEV,/FVC 82 t 5%. The MVV was 165 t 46 l/min (percent predicted 108 t 14%). The study was approved by the appropriate Institutional Review Boards, and informed consent was obtained from all subjects. Apparatus. The subjects breathed through a two-way nonrebreathing valve of low resistance and dead space (model 2600, Hans Rudolph). Inspiratory flow was measured with a pneumotachograph (model 3813, Hans Rudolph) and a k5 cmH,O differential pressure transducer (Validyne MP-45). Tidal volume (VT) was obtained by integration of the flow signal. Expired gas was passed through a mixing chamber and analyzed for 0, and CO, by a paramagnetic 0, analyzer (ADC) and an infrared CO, analyzer (ADC), respectively. The heart rate (HR) was determined from the electrocardiograph. The electrical signals from the recording amplifiers were connected to a microprocessor that performed analog-to-digital conversions and calculated average values of inspired ventilation (VI), VT, respiratory frequency (f), 0, uptake (VO,), CO, production (VCOJ, and HR every 30 s. The values were continu-
Copyright 0 1991 the American Physiological Society
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ously printed and simultaneously stored on disk. The inspiratory flow signal was recorded on a strip chart recorder (Gould), and inspiratory time (TI), expiratory time, and fractional inspiratory time (TI/TT) were measured by hand from this tracing. Expired CO, was sampled at the mouthpiece and analyzed by a second infrared CO, analyzer (Beckman, Medical Gas Analyzer, LB-2) andwas recorded breath-by-breath on the strip chart recorder. End-tidal CO, (FETED,)I was measured from this tracing. All equipment was calibrated before each exercise test. 0, and CO, analyzers were calibrated with two test gases of known composition. The pneumotachograph was calibrated with a volume calibration syringe. Inspiratory resistance of the exercise circuit was 1.7 cmH,O 1-l. s at a flow of 60 l/min and 2.2 cmH,O 1-l. s at a flow of 120 l/min. Expiratory resistance was 0.7 cmH,O?* s at flows of 60 and 120 l/min. MVV measured directly on the exercise circuit in five of the subjects was 106.3 t 4.4% of spirometer MVV. The sensation of respiratory effort was assessed with a visual analog scale (VAS) (2) consisting of a vertical straight line 100 mm in length labeled “breathing very very light” at the bottom and “breathing very very hard” at the top. Subjects were instructed to point to a spot on the line indicating the intensity of their sensation of respiratory effort at that particular point in time (an attendant made the actual mark on the line). VAS measurements were obtained every minute during exercise. The subjects were specifically instructed to scale their “effort to breathe” and to disregard any other sensations associated with whole-body exercise. Exercise testing. Subjects were studied on four separate occasions. On the 1st day a preliminary incremental exercise test was performed on an electronically braked cycle ergometer (Rodby Electronik) to determine the maximal work capacity (Wmax) for each subject. After 1 min of unloaded cycling, the work load was increased by 25 W every minute until the subject could no longer continue. The last work load for which the subject was able to complete the full minute of cycling was designated Wmax. On the 2nd, 3rd, and 4th experimental days, the subject exercised on the same cycle ergometer. Th .e subjects were allowed 2-3 min to acclimatize to the breathing circuit and then exercised for 2 min at 50 W (warm-up period) before initiating exercise at 90% of Wmax. The subjects exercised at 90% of Wmax until they were no longer able to maintain the pedaling frequency above 40 rpm. On day 3 t exercise was performed after induction of inspiratory muscle fatigue, whereas exercise alone was performed on days 2 and 4 (controls). All exercise tests were separated by 22 days. Znspiratory loading. The subject’s maximal mouth pressure (Pm,,,) was measured with a differential pressure transducer (Validyne t350 cmH,O) while.performing a maximum inspiratory effort against an occluded airway ne ar residual volume (7). The pressure transducer was calibrated with a me rcury manometer before each study. To prevent glottic cl0 sure, a small le ak was produced by i nsertion of an 18 -gauge needle in the mouthpiece. Pm maxmaneuvers were repeated unti 1 three reproducible measurements that were sustained for at least 1 s were recorded. The highest value obtained was l
l
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used for analysis. After completion of the Pmmax maneuvers, the subjects were instructed to breathe against an inspiratory threshold load. Threshold loading was performed using the technique of Nickerson and Keens (20). All subjects practiced on the threshold load for one or more sessions before initiation of the experimental protocol. With this technique, initiation of airflow requires development of a level of pressure sufficient to lift a plunger that in the fully dependent position occludes the orifice of an otherwise sealed cylinder. Weights were added to the plunger so that the subjects were required to generate 80% of their Pmmax to initiate airflow. Expiration was unloaded, and the subjects were allowed to choose their own breathing pattern. TI/TT adopted during threshold loading was 0.56 t 0.08 (range 0.50-0.71). The target pressure was maintained for 280% of the inspiratory effort in every subject until the final minute of threshold loading (when task failure started to show). The endurance time was calculated as the time from the start of the run until the subject was no longer able to generate the target pressure in a square-wave fashion for five consecutive breaths. In this experiment, endurance time was 15.3 t 7.3 min. When the subject was unable to generate the target pressure for five consecutive inspiratory efforts, all the inspiratory muscles including the diaphragm were considered to be fatigued. Data analysis. To account for the variation in duration of exercise between subjects and between trials, the following analysis was performed. First, the last minute of exercise during the control trials was compared with the last minute of exercise after the induction of fatigue. Second, the last minute of exercise during the shortest exercise trial was compared with the equivalent time period during the other two exercise trials (isotime comparison). Comparisons were made by one-way analysis of variance with a repeated measures design. If the overall analysis of variance was significant, the two control runs were compared with each other to determine whether the experimental protocol itself affected the response to exercise due to either a training or learning effect. Because there were no significant differences between the control trials, the average of the two control trials was then compared with the fatigue trial. P = 0.025 was considered significant [Bonferroni correction for multiple (two) comparisons]. The results are expressed as means t SD unless otherwise stated. RESULTS
During the preliminary incremental exercise test, Wmax was 215 t 34 W and maximal 0, uptake (vo2 ,,,) was 2.54 t 0.45 l/min (36.6 t 5.4 ml min. kg-‘). No significant differences were observed in any of the measured parameters between the two control trials. The induction of inspiratory muscle fatigue produced a fall in Pm,,, in every subject from a baseline value of 138 t 33 to 110 t 31 cmH,O (P < 0.005) (79.7% of baseline value). Induction of inspiratory muscle fatigue also caused a reduction in exercise duration, 238 t 69 s, compared with both control periods, 302 t 87 (control 1) and 319 t 108 (control 2) (P < 0.001) (Fig. 1). This represents a 23% reduction in exercise duration. l
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TABLE 2. Isotime comparison of cardiorespiratory parameters during exercise after induction of fatigue compared with control
1
500
Control
‘0‘ VO,, ml/min VI, l/min VT, liters
f, breaths/min TI, s TE, s TI/TT VT/TI, l/s VAS, mm FETCO,, %
100 A
I
Control FIG.
1. Exercise duration of fatigue. Exercise of fatigue.
1
I
Post
Control 2
Fatigue
I induction induction
for each subject during control and after duration was significantly reduced after
1. Cardiorespiratory parameters during last minute of exerise after induction of fatigue compared with control TABLE
Control
HR,
beats/min
VI, l/min
VAS, mm FETCO,, 5%
2,601&43 3,028-t509 174t14 91.7k16.9 82+25 5.OkO.6
1
Control
2,473&518 3,052-+623 180&B 92.4k21.3 85218 5.2-t0.5
2
2,388&563 78.1k18.4 2.63kO.77 30.8k6.5 0.91kO.22 0.93kO.21 0.49+0.05 2.80k0.68 73k24 5.4kO.5
1
Control
Fatigue
2
2,336&447 78.3k 17.5 2.7OkO.84 30.7k7.4 0.95kO.27 1.03kO.34 0.49kO.05 2.78kO.70 69k17 5.620.7
2,234+472 87.2+17.9* 2.5OkO.81 36.8+8.5* 0.78&O. 18 0.82k0.217 0.49-+0.04 3.13+0.75t 83+26$ 5.1kO.3
Values are means + SD of 10 subjs. f, respiratory frequency; TI, inspiratory time; TE, expiratory time; TI/TT, fractional inspiratory time; VT/TI, mean inspiratory flow; see Table 1 footnote for definition of other abbreviations. Significant difference from average of control 1 and 2 values: * P < 0.001, t P < 0.01, $ P < 0.025.
The last minute of exercise after induction of fatigue was compared with the last minute of exercise during the control trials (Table 1). VO, was significantly less after induction of fatigue compared with control (Table 1) (P < 0.002). Similarly, VCO, and HR were both lower after induction of fatigue compared with control (P < 0.002 for both comparisons; Table 1). The respiratory quotient and FET,,, were not significantly different after induction of fatigue compared with control. There were also no significant differences in any of the breathing pattern components including VI after induction of fatigue. The VAS for respiratory effort was also similar after induction of fatigue compared with control (Table 1). Isotime comparisons yielded quite different results (Table 2). VO, was similar after induction of fatigue compared with control (Table 2, Fig. 2). Similarly, there were no significant differences in VCO, or HR after induction of fatigue. This indicates that the rate of increase in these metabolic parameters during exercise was similar after induction of fatigue compared with control. Thus the lower Vo2, which we observed after induction of fatigue, was solely due to the shorter exercise duration. Isotime VI was significantly greater after induction of
VO,, ml/min VCO,, ml/min
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Fatigue 2,234+472* 2,824+538* 167k15* 87.4+18.1 83_+26 5.1kO.3
Values are means + SD of !O subjs. %Jo2, 0, consumption; %o,, CO, production; HR, heart rate; VI, minute ventilation; VAS, visual analogue scale for respiratory effort; FET,,,, end-tidal COz. * Significant difference from average of controZ I and 2 values (P < 0.002).
fatigue compared with control (P < 0.002) (Table 2). FET,,, tended to be lower after induction of fatigue compared with control (P < 0.09). The increase in VI was due to an increase in f after induction of fatigue (P < 0.0001) (Table 2). VT, in fact, tended to be slightly lower after induction of fatigue compared with control (P < 0.04). The increase in f was due to a decrease in both expiratory time (P < 0.006) and TI after induction of fatigue, although the change in TI did not reach statistical significance. TI/TT remained unchanged after induction of fatigue. Mean inspiratory flow (VT/TI), a crude index of respiratory drive, increased after induction of fatigue compared with control (P < 0.003) (Table 2). VAS scores were reproducible at end exercise and exercise isotime (coefficient of variation for the 2 control trials was 4.1 t 2.2% at end exercise and 12.0 t 3.1% at exercise isotime). The isotime VAS for respiratory effort increased after induction of fatigue (Table 2) (P < 0.025). The increase in VAS was proportional to the increase in VI so that the slope and position of the VAS-VI relationship was not significantly altered by induction of fatigue. The slope of the VAS-VI relationship was 1.30 t 0.31 during control compared with 1.22 t 0.36 mm 1-l. min after induction of fatigue (P = NS). The VAS at a VI of 50.0 l/min was 40.3 t 11.1 during control compared with 39.4 t 19.5 mm after induction of fatigue (P = NS), indicating that the position of the VAS/VI relationship was not altered by the induction of fatigue. The time course of changes during exercise in Vo2, f, VT, and VI after induction of fatigue compared with control are shown in Fig. 2. In Fig. 2, the beginning, middle, and final minutes of the fatigue exercise trial are compared with the same time period during the control trials. At any given isotime, 00, was similar after induction of fatigue compared with control. At the beginning and middle of the fatigue exercise trial, VT was similar to isotime control VT. At the end of the fatigue exercise trial, VT tended to be smaller than isotime control VT (P < O.O4), although this difference did not reach statistical significance. The time course of changes in the VAS for respiratory effort is shown in Fig. 3. At the beginning of the exercise trials, the VAS scores were not significantly l
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-
25
B
o-0Control
F.- 80 \E G 60 40 IO C
I’
1 6
I
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I5
D
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FIG. 2. 0, consumption (vo2), minute ventilation #I), tidal volume (VT), and respiratory frequency (f) during the 1st min (B), the middle minute (M), and the final minute (E) of exercise after induction of fatigue (V) and during the same time period (isotime) in the absence of fatigue (control, 0). Values are means f SE of 10 subjs. Control curve represents average of 2 control trials. *Significant difference from average of 2 control trials (P < 0.01). At any given time during exercise, VI and f after induction of fatigue were greater than control values.
different after induction of fatigue compared with control. At the middle and end of the fatigue exercise trial, the VAS score for respiratory effort was higher than the isotime control VAS score.
We made considerable efforts to exclude motivation as a factor by choosing only highly motivated subjects and by constantly encouraging the subjects during the loaded breathing runs. Studies employing a similar protocol and definition of fatigue but with measurement of DISCUSSION transdiaphragmatic pressure generation in response to The major findings in this study were as follows: 1) phrenic nerve stimulation have invariably shown the deacute induction of inspiratory muscle fatigue resulted in velopment of peripheral low-frequency fatigue, as dema decrease in exercise duration and 2) after induction of onstrated by a reduction in transdiaphragmatic presfatigue, relative tachypnea was observed during high-insure at the low physiological frequencies of stimulation tensity exercise. (4, 5, l&19). Critique of methods. The question arises as to whether Subsequent to this experiment, we have examined the our subjects developed inspiratory muscle fatigue, be- tension-time index of the diaphragm and of the rib cage cause our study design did not include an independent in subjects undergoing loaded breathing trials identical measure of fatigue. We employed a method similar to to those performed in this study. The tension-time inthat of Roussos et al. (25) and others (1,4,5,12,18,19) dex of the diaphragm was 0.28 t 0.05 and exceeded the for the induction of inspiratory muscle fatigue. In these fatigue threshold for the diaphragm of 0.15-0.18 (6) in experiments , it was fou nd that a mouth pressure exceed- every trial (29 trials in 7 subjects). Similarly, the tening 60% of maxim urn could not be sustained indefision-time index of the rib cage was 0.38 t 0.06 and exnitely. Extrapol ating from the definition of. skeletal ceeded the fatigue threshold for the rib cage of 0.26-0.30 muscle fatigue, i. e., the inability to maintain a predeter(11) in every subject (M. J. Mador, unpublished obsermined load, Roussos an d Ma .cklem considered that all vations). On the basis of the above points, we are confithe ins piratory must les were fatigued when the subject dent that fatigue of the inspiratory muscles was could no longer achieve the target mouth pressure by achieved in our subjects. any means. The inability to generate the required presExercise Limitation. After induction of inspiratory mussure could be due to motivational factors, peripheral cle fatigue, the ability to perform high-intensity exercise muscle contractile fatigue (peripheral fatigue), or a re- was impaired. Exercise duration fell by 23% after induction of fatigue compared with control (Fig. 1). This reduction in central neural motor drive (central fatigue). Downloaded from www.physiology.org/journal/jappl by ${individualUser.givenNames} ${individualUser.surname} (163.015.154.053) on August 7, 2018. Copyright © 1991 American Physiological Society. All rights reserved.
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o-0Control 0-o Fatigue
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80 i
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FIG. 3. Visual analogue scale for respiratory effort (VAS) during the 1st minute (B), the middle minute (M), and the final minute (E) of exercise after induction of fatigue (0) and during the same time period (isotime) in the absence of fatigue (control, 0). Values are means + SE of 10 subjs. Control curve represents average of 2 control trials. “Significant difference from average of 2 control trials (P < 0.025). At the middle and end of exercise after induction of fatigue, VAS score for respiratory effort was higher than isotime control VAS score.
duction in exercise duration was associated with a lower that. inspiratory muscle fatigue can 2 max) indicating prevent attainment of V02max during exercise. It would be of interest to see if a similar or even greater decrease in exercise duration occurs after induction of fatigue by voluntary hyperpnea, an activity that more closely approximates the demands placed on the ventilatory pump by exercise. The difference in exercise tolerance could not have been due to a learning or training effect related to the exercise protocol because there was no significant difference between the control trials performed several days before and several days after the fatigue run. It could be argued that, because of the exhausting nature of threshold loaded breathing to fatigue, our subjects did not put forth as good an effort after induction of fatigue compared with control. However, at end exercise, VI and VT/ TI were similar after induction of fatigue compared with control (Table 1), implying that the degree of respiratory effort was at least equal if not greater after induction of fatigue (because induction of fatigue was associated with mild respiratory muscle weakness). Furthermore, the respiratory quotient at end exercise was similar after induction of fatigue (1.29 t 0.18) compared with control (1.21 t O.l3), suggesting that skeletal muscle effort was not substantially different under the two circumstances. There are a number of additional potential mechanisms by which induction of inspiratory muscle fatigue might impair subsequent exercise performance. High-intensity exercise might itself be fatiguing to the inspiratory muscles, as has been suggested by other investigators (8, 14). If this were the case, one might expect greater alterations in the function of muscles that were already fatigued compared with those in the fresh state. This greater muscle dysfunction could in turn limit the ventilatory response to exercise, resulting in premature termination of the exercise trial. However, in this study, the ventilatory response to exercise was actually enhanced after induction of fatigue. Thus the degree of vo
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muscle dysfunction induced by inspiratory muscle fatigue in this study was not sufficient to produce a ventilatory limitation to exercise. VI increased markedly during exercise. This increase in VI is achieved by an increase in respiratory muscle work. As the respiratory muscles work harder, they consume more 0,. Bye and colleagues (9) have speculated that during heavy exercise, 0, consumption by the respiratory muscles may reduce the amount available to the exercising skeletal muscle, thus limiting exercise performance. However, recent estimates of the 0, cost of ventilation suggest that at a ventilation of -100 l/min the 0, cost of ventilation is between 1.5 and 2.5 ml/l of ventilation (3). Because at exercise isotime, v, was -9 l/min greater after induction of fatigue than during control, the cost of this added ventilation would be 23 ml/min, a trivial amount that is unlikely to have influenced exercise endurance. It could be argued that induction of fatigue by producing mild muscle weakness may have reduced inspiratory muscle efficiency. Induction of fatigue may also have depleted the inspiratory muscles of their nutrient stores, increasing their requirement for delivered 0,. These factors could increase the 0, cost of ventilation. However, if the 0, cost of ventilation was truly increased after induction of fatigue, VO, during submaximal exercise should have been larger after induction of fatigue than during control. This was not the case (Fig. 2), indicating that this mechanism is unlikely to have played a major role in our study. For any given level of inspiratory pressure, the sensation of respiratory effort is greater after induction of fatigue than during control (13). In this study, the isotime VAS for respiratory effort was larger after induction of fatigue than during control. Thus our subjects could have stopped exercise prematurely after induction of fatigue because of a greater sense of respiratory effort. In a previous study by Martin and colleagues (17) in which subjects performed a highly rigorous but probably nonfatiguing task (subjects hyperventilated at their volitional maximum for 150 min), subsequent incremental treadmill exercise was terminated prematurely compared with control exercise. This decrease in exercise performance appeared to be due to an increase in unpleasant respiratory sensations, although sensation was not objectively quantified. Similarly, the subjects of Bye and colleagues (8), who performed high-intensity exercise (80% of Wmax) until volitional exhaustion, complained predominantly of dyspnea at end exercise. In our study, at exercise isotime the VAS for respiratory effort was indeed larger after induction of fatigue than during control. It is of interest that our subjects reported that they stopped exercise predominantly because of leg fatigue rather than dyspnea. However, at end exercise the VAS scores for respiratory effort were quite high, exceeding 80 mm in nine of the subjects and 90 mm in six of the subjects. It is likely that both leg and respiratory sensations contributed to exercise termination in our subjects. Therefore we believe that an increase in the sense of respiratory effort during exercise is the most likely explanation for our subject’s decreased exercise tolerance after induction of inspiratory muscle fatigue. In turn, this increase in the sense of respiratory effort appears to be largely because
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of the enhanced ventilatory response to exercise induced by inspiratory muscle fatigue. Respiratory motor output and respiratory sensation. At exercise isotime, VI and VT/TI were greater after induction of fatigue than during control (Table 2). Increases in VI and VT/TI after induction of fatigue indicate an increase in central respiratory drive, albeit this increase may be underestimated. A portion of this increase in drive was presumably compensatory in nature, maintaining VI in the presence of mild muscle weakness (P m maxfell by 20% after induction of fatigue). However, at exercise isotime, VI was larger after induction of fatigue than during control, indicating an additional stimulus to ventilation. We have obtained similar results in a previous study in which we examined the effects of inspiratory muscle fatigue on the breathing pattern during incremental exercise (1). Stimulation of thin fiber afferents within the diaphragm results in an increase in diaphragmatic electrical activity (22), and we speculated that these fibers may have been responsible for the increase in respiratory drive that we observed, as has previously been suggested (23). At exercise isotime, the VAS for respiratory effort was greater after induction of fatigue than during control (Table 2). As described above, both VI and VT/TI were increased after induction of fatigue, indicating an increase in central motor drive. Our subjects were able to perceive this increase in respiratory effort as indicated by the increase in VAS measurements after induction of fatigue. In an attempt to determine whether fatigue altered the perception of respiratory effort independent of alterations in central motor drive, we examined the relationship between the VAS for respiratory effort and VI during control and after induction of fatigue. Neither the slope nor position of the VAS-VI relationship was altered by induction of fatigue. Therefore the increase in VAS measurements after induction of fatigue in this study may be explained by the increase in central respiratory drive and no additional mechanisms need be invoked. Pattern of breathing. At exercise isotime, a pattern of rapid shallow breathing was observed after induction of fatigue compared with control. A similar pattern of breathing has been observed after induction of fatigue in both an anesthetized (23) and awake animal preparation (21). Rapid shallow breathing has also been observed after induction of fatigue in human subjects (10, 12). However, we were unable to elicit rapid shallow breathing after induction of fatigue in healthy human subjects during resting unstimulated breathing (1, 16). In contrast, when we increased VI by incremental leg exercise, a pattern of rapid, albeit not shallow, breathing became apparent at the higher work loads (1). During resting unstimulated breathing, the ventilatory pump had considerable reserve even after the induction of f@igue. In contrast, during high-intensity exercise, the ventilatory pump is stressed to a considerably greater degree, and the changes in breathing pattern consequent to inspiratory muscle fatigue may then become more apparent. In this study, we also observed rapid and a tendency towards shallow breathing during high-intensity exercise after induction of fatigue. Interestingly, tachypnea was observed even during the 1st min of exercise after induc-
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tion of fatigue when VI was only 35.97 -t 6.20 l/min (Fig. 2). This VI is lower than that required to produce tachypnea in our previous study (1). However, because of the nature of the studies, the time elapsed from induction of fatigue to exercise at high work loads was much shorter in this study (5 min vs. 12 min), and this likely accounts for the greater ease with which tachypnea was elicited. The mechanism by which inspiratory muscle fatigue elicits rapid shallow breathing has not been fully delineated. Potential mechanisms have been discussed previously (1, 12, 21, 23, 24). In summary, induction of inspiratory muscle fatigue impaired subsequent performance of high-intensity constant-work-load leg exercise. In addition, induction of inspiratory muscle fatigue increased the ventilatory response to exercise and altered the pattern of breathing, producing tachypnea and increasing the sense of respiratory effort (VAS) for a given exercise isotime. We suggest that the reduction in exercise performance after induction of fatigue may be due to an increase in the sensation of respiratory effort during exercise consequent to the enhanced ventilatory response to exercise induced by inspiratory muscle fatigue. The authors thank Diane Poch for preparation of the manuscript, John Jankowski for technical assistance, and Dr. M. J. Tobin for careful review of the manuscript. This study was supported by grants from the American Lung Association of New York and American Heart Association of New York, an institutional grant from the State University of New York at Buffalo, and Veterans Administration Medical Research Funds. Address for reprint requests: M. J. Mador, Pulmonary Div., Dept. of Medicine, School of Medicine, Veterans Administration Medical Center, 3495 Bailey Ave., Buffalo, NY 14215. Received 30 March 1990; accepted in final form 19 December 1990. REFERENCES
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