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Skeletal Muscle and Exercise |
1 Department of Critical Care Medicine and Pulmonary Services, Evangelismos Hospital, ‘M. Simou and G. P. Livanos Laboratories’
2 Department of Physical Education and Sport Sciences
3 Department of Respiratory Medicine, National and Kapodistrian University of Athens, Greece
4 Department of Medicine, University of California, San Diego, CA, USA
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Abstract |
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: 70.0 ± 1.6 ml kg–1 min–1; mean ±S.E.M.) completed, in a balanced ordering sequence, one normoxic (end-exercise arterial O2 saturation (Sa,O2): 92 ± 1%) and one hyperoxic (FI,O2: 0.5% O2; Sa,O2 : 97 ± 1%) 5 min exercise test at intensities equal to 80 ± 3 and 90 ± 3% of maximal work rate (WRmax), respectively, producing the same tidal volume (VT) and breathing frequency (f) throughout exercise. Cervical magnetic stimulation was used to determine reduction in twitch transdiaphragmatic pressure (Pdi,tw) during recovery. Hyperoxic exercise at 90% WRmax induced significantly (P= 0.022) greater post-exercise reduction in Pdi,tw (15 ± 2%) than did normoxic exercise at 80% WRmax (9 ± 2%), despite the similar mean ventilation (123 ± 8 and 119 ± 8 l min–1, respectively), breathing pattern (VT: 2.53 ± 0.05 and 2.61 ± 0.05 l, f: 49 ± 2 and 46 ± 2 breaths min–1, respectively), mean changes in Pdi during exercise (37.1 ± 2.4 and 38.2 ± 2.8 cmH2O, respectively) and end-exercise arterial lactate (12.1 ± 1.4 and 10.8 ± 1.1 mmol l–1, respectively). The difference found in diaphragmatic fatigue between the hyperoxic (at higher leg work rate) and the normoxic (at lower leg work rate) tests suggests that neither EIAH nor lactic acidosis per se are likely predominant causative factors in diaphragmatic fatigue in this population, at least at the level of Sa,O2 tested. Rather, this result leads us to hypothesize that blood flow competition with the legs is an important contributor to diaphragmatic fatigue in heavy exercise, assuming that higher leg work required greater leg blood flow.
(Received 16 December 2005;
accepted after revision 25 January 2006;
first published online 26 January 2006)
Corresponding author I. Vogiatzis: Thorax Foundation, 3 Ploutarhou Str. 106 75, Athens, Greece. Email: gianvog{at}phed.uoa.gr
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Introduction |
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85%
) induces diaphragmatic fatigue in subjects with varying degrees of fitness levels, as evidenced by a substantial reduction in twitch transdiaphragmatic pressure (Pdi,tw) (Johnson et al. 1993). It has been hypothesized that exercise-induced diaphragmatic fatigue is dependent on several factors namely: (a) high diaphragmatic workload (Johnson et al. 1996) (b) arterial hypoxaemia (Babcock et al. 1995a; Gudjonsdottir et al. 2001) and (c) competition for blood flow between the diaphragm and the locomotor muscles associated with an increased production of metabolic byproducts by the active musculature (Fregosi & Dempsey, 1986; Johnson et al. 1996). More recently, Babcock et al. (2002) have shown that in healthy subjects diaphragmatic fatigue during high-intensity whole-body exercise depends on the relationship between the magnitude of work incurred by the diaphragm and the adequacy of its blood and/or oxygen supply. In addition, there is evidence that diaphragmatic fatigue also occurs in highly fit athletes during exhaustive exercise (Babcock et al. 1996). Since during high-intensity exercise 40–50% of highly trained athletes exhibit exercise-induced arterial hypoxaemia (EIAH) (Powers et al. 1988; Dempsey & Wagner, 1999; Nielsen et al. 2002), the present study was designed to investigate whether near the maximal levels of exercise (WRmax), when cardiac output is maximal (Mortensen et al. 2005), arterial hypoxaemia per se or blood flow competition between the respiratory and locomotor muscles is more important in causing diaphragmatic fatigue in this highly fit population. To answer this question, highly trained cyclists exercised at two different work intensities (80% and 90% WRmax) under hypoxaemic and normoxaemic conditions, respectively. The experimental design aimed at comparing the degree of diaphragmatic fatigue under two exercise conditions, where arterial oxygen tension and leg work rate varied while maintaining respiratory muscle load similar. Since diaphragmatic power output contributes importantly to exercise-induced diaphragmatic fatigue (Johnson et al. 1996), control of respiratory load within the present experimental design was important in order to isolate the effect of hypoxaemia per se on diaphragmatic fatigue in highly trained athletes. We reasoned that under these conditions, if the hypoxaemic run (at lower leg work rate) produced more fatigue, this would point to arterial hypoxaemia as a prime cause for fatigue. However, if there was more fatigue in the normoxaemic run (at higher leg work rate), this would be compatible with the hypothesis that fatigue was related more to respiratory muscle blood flow limitations. This in turn is based on the presumption that a higher leg effort (90%versus 80% WRmax) would require greater leg blood flow (as the work of Mortensen et al. (2005) has recently demonstrated), potentially reducing flow available to the respiratory muscles (as the work of Harms et al. (1998) suggests may be the case).
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Methods |
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Ten male highly trained national team cyclists, with a maximal oxygen uptake 
of 70.0 ± 1.6 ml kg –1 min–1 participated in the study. Physical characteristics of the subjects are presented in Table 1. Prior to participation in the study all subjects were informed of any risks and discomforts associated with the experiments, and signed an informed consent. The study was approved by the authors' University Ethics Committee and conducted in accordance with the guidelines of the Declaration of Helsinki.
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Experiments were conducted in three visits (Fig. 1). In visit 1, subjects underwent an incremental exercise test to the limit of tolerance. This test was carried out in room air. On the basis of the subjects' percentage oxygen saturation (%Sp,O2) at the end of this test, EIAH was confirmed by a fall in %Sp,O2 of 4% below resting values (Dempsey & Wagner, 1999) (Table 1). In visit 2 (on a different day) subjects completed a second incremental test to the limit of tolerance, breathing a high fraction of inspired O2 (FI,O2: 50% O2) gas mixture. This allowed maximal workload to be established both under normoxaemic and hypoxaemic conditions for all 10 subjects. In visit 3 (Fig. 1) subjects completed, in a balanced ordering sequence, two 5 min exercise tests separated by 90 min, either at an intensity initially set at 80% WRmax (LO) of the first incremental test in room air, or at an intensity initially set at 90% WRmax (HI) of the second incremental test while breathing a high FI,O2 (50% O2). In this manner all subjects completed a 5 min high-work rate normoxaemic test and a 5 min lower work rate hypoxaemic test in a well-balanced sequence assuring equal numbers of either sequence.
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The incremental exercise tests were performed on an electromagnetically braked cycle ergometer (Ergoline 800; Sensor Medics, Anaheim, CA, USA) starting at 20 W and increasing by 20 W every minute, with the subjects maintaining a pedalling frequency of 70–90 r.p.m. Tests were preceded by a 3 min rest period, followed by 3 min of unloaded pedalling. The following pulmonary gas exchange and ventilatory variables were recorded breath-by-breath (Vmax 229; Sensor Medics, Anaheim, CA): oxygen uptake 
, carbon dioxide elimination 
, respiratory exchange ratio (RER), minute ventilation 
, tidal volume (VT), and breathing frequency (f). Heart rate (HR) and %Sp,O2 were determined using the R–R interval from a 12-lead online electrocardiogram (Marquette Max; Marquette Hellige GmbH, Germany) and a pulse oximeter (Nonin 8600; Nonin Medical, USA), respectively.
HI and LO exercise tests
During these tests, measurement of pulmonary gas exchange was performed as mentioned above. Arterial blood was taken every minute throughout the exercise tests, whereas continuous monitoring of oesophageal pressure (Poes), gastric pressure (Pga), and swings in transdiaphragmatic pressure (
Pdi), averaged over 20 s breath samples every minute, was also performed throughout the exercise tests. Tests were always preceded by 5 min of warm-up cycling at 50%
in room air. In order to match the ventilatory requirement between the two 5 min exercise tests, the work rate of the second test was adjusted to produce the same 
as during the first 5 min exercise test.
Assessment of diaphragmatic fatigue
To assess diaphragmatic fatigue, Pdi,tw was measured before and 10, 20, 40 and 60 min following the two exercise tests. Pdi,tw was obtained by subtracting Poes from Pga, which were assessed by two commercially available balloon catheters cut to 110 cm (Ackrad Laboratories, Inc, Crandford, NJ, USA). The balloons were inserted by nasal intubation following the application of 2% lidocaine anaesthetic gel to the nose and, with the assistance of continuous pressure monitoring, the two balloon tips were positioned in the oesophagus and stomach, respectively. Monitoring of the pressures was performed with the use of Validyne MP45 transducers (Validyne Corporation, Northridge, California, USA), and the pressure signals were recorded and analysed using a Direc Win recorder (model 218A).
At rest and during recovery, Pdi,tw was recorded during stimulation of the phrenic nerves at the neck according to recommended techniques (Hamnegard et al. 1996; Polkey et al. 1998; Mador et al. 2000, 2002; Man et al. 2004). The phrenic nerve roots were bilaterally stimulated with cervical magnetic stimulation (CMS) using a Magstim 200 magnetic stimulator with a circular (doughnut-shaped) 90 mm coil (9450-23-P12) with a maximum magnetic field of 2.3 T (Magstim Whitland, Dyfed, UK). To optimize the position of the coil and the accuracy of measurement, the neck was flexed. Several stimulations were conducted over the spinal processes at varying power outputs in the midline between C5 and C7, in order to determine correctly the position on the neck at which the maximal response could be elucidated (Hamnegard et al. 1996; Mador et al. 2002). Supramaximal stimulation was indicated by a plateau in Pdi,tw with increasing power output (Mills et al. 1995, 1996; Mador et al. 2000, 2002). Then, the position of magnetic stimulation on the neck was marked with an indelible marker and thereafter all measurements were conducted at the exact same position and at full stimulator output. During recovery the correct position on the neck was re-evaluated and confirmed by a plateau in Pdi,tw after supramaximal stimulation. To avoid twitch-on-twitch potentiation, adjacent measurements were performed 30 s apart (Wragg et al. 1994). The magnetic stimulation was performed with the subject in a seated position, with a nose clip on and with the mouth closed. Subjects were instructed to breathe quietly, then to perform a gentle expiratory effort to functional residual capacity (FRC) and to hold their breath while the magnetic stimulation took place. We relied on Poes as a measure of position in the respiratory cycle relative to FRC. Hence, Poes immediately before stimulation was always carefully evaluated to ensure constant lung volume (Mills et al. 1995, 1996; Hamnegard et al. 1996; Polkey et al. 1998; Mador et al. 2002). Once relaxation was achieved (as judged by leveling off of Pdi and Poes) the operator performed the stimulation. Twitch responses were rejected for analysis when Poes immediately before stimulation was more than 1 cmH2O pressure difference from that at FRC (Roussos et al. 1979). Continuous feedback of Poes was provided via the computer screen. A total of 10 measurements at each time point were conducted at full magnetic output and the average value of the five best measurements was used for the analysis.
Arterial blood gas measurements
Arterial tensions of O2(Pa,O2), and CO2(Pa,CO2), pH and percentage arterial oxygen saturation (%Sa,O2) were measured from 2 ml blood samples on a blood gas electrode system combined with a co-oximeter (ABL 625, Radiometer, Copenhagen, Denmark) within 10 min of collection. Blood samples, taken every minute during the 5 min tests and 10 and 60 min into recovery, were kept on ice prior to measurement. The blood gas analyser was auto-calibrated every 4 h throughout the day, and calibrating gases of known concentrations were run before each set of measurements. Blood gas measurements were corrected for the subject's tympanic temperature taken during withdrawal of each arterial blood gas sample.
Statistical analysis
All data are reported as mean ±S.E.M. Paired and independent t tests were employed to determine differences in baseline characteristics within and between groups, respectively. Two-way ANOVA with repeated measures was used to identify statistically significant differences across different time points between the HI and LO intensity exercise tests for each variable. When overall significance was obtained, differences between conditions were identified with the Tukey's post hoc test. With respect to Pdi,tw values at baseline and at the 10th and 20th minute of recovery, where for each subject the five best measurements within each time point and condition were considered, a mixed effect model (Laird & Ware, 1982) was used to account for the subject's variability in Pdi,tw. Linear regression analysis was performed using the least squares method. The level of significance was set at P < 0.05.
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Results |
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Table 1 shows the subjects' responses to both incremental exercise tests. All subjects demonstrated a reduction in %Sp,O2 4% at the end of the incremental exercise tests in room air. At the end of the second incremental test while breathing the high 
, WRmax, 
, fmax and %Sp,O2 were significantly different compared to the test in room air (Table 1).
High workload (HI) and low workload (LO) exercise
The mean workload achieved in the two 5 min tests represented 80 ± 3% (LO) and 90 ± 3% (HI) WRmax achieved in the incremental exercise tests in room air. Mean workload throughout the HI test was significantly (P= 0.001) greater than the LO test (Fig. 2A). Subjects reached a plateau in 
at the last 2 min of the LO and HI tests, with a mean 
of 65.6 ± 2.6 and 72.0 ± 2.3 ml kg min–1, respectively, that corresponded to 94 ± 2 and 103 ± 3% of 
of the incremental exercise test in room air, respectively (Fig. 2B). 
was significantly higher in the HI compared to the LO test (P= 0.010), whereas HR was not different between the two tests, reaching, at the last minute of both exercise tests, 94 ± 2% of maximum (Fig. 2C) recorded during the incremental exercise test in room air.
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The ventilatory response to the exercise tests is shown in Fig. 3. 
increased with exercise in both tests, reaching a maximum value at the end of exercise that corresponded to 85 ± 5% of the maximum value attained at the incremental test in room air (Fig. 3A). No significant differences were found in 
between the two tests. Neither VT nor f differed between the two tests (Fig. 3B and C).
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Throughout both exercise tests %Sp,O2, Pa,O2 and Pa,CO2 were significantly (P < 0.001) higher in the HI versus the LO tests (Fig. 4A–C), whereas arterial lactate, pH and body temperature were not significantly different (Fig. 4D–F). Arterial lactate and pH did not differ 10 min into recovery (Fig. 4E and F) and returned to baseline levels within 60 min of recovery. Changes in Pa,CO2 throughout both HI and LO tests were not correlated with the degree of fall in post-exercise Pdi,tw.
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Figure 5 shows the mean changes in Pdi during the HI and LO intensity exercise test. No differences were found in Pdi during the two exercise tests. Mean Pdi values during the HI and LO tests were 37.1 ± 2.4 and 38.2 ± 2.8 cmH2O, respectively.
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Discussion |
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Respiratory muscle loading during the HI and LO tests
Factors leading to diaphragmatic fatigue have been suggested to include increased work by the diaphragm and reduced blood flow/oxygen availability (Babcock et al. 2002). It has been shown that hypoxaemia superimposed on high-intensity exercise hastens diaphragmatic fatigue during exercise (Babcock et al. 1995a, 1995b; Gudjonsdottir et al. 2001). However, hypoxaemia also stimulates ventilation, so that this strategy created not only hypoxaemia but also increased respiratory muscle load, making the role of hypoxaemia difficult to isolate. The key design feature of the present study was to control for respiratory muscle load by matching tidal volume, frequency and ventilation in normoxia and hyperoxia by adjusting leg work rate. Greater fatigue in hypoxaemic conditions would then point to the importance of Pa,O2 in diaphragmatic fatigue. Conversely, based on the suggestion that at high work rates there is competition for perfusion between the diaphragm and legs (Johnson et al. 1996), we reasoned that at the higher exercise intensity in normoxaemia, diaphragm blood flow might be compromised and lead to greater fatigue if blood flow and not Pa,O2 were more important, and that is what we found.
Effect of arterial hypoxaemia on diaphragmatic fatigue
In both exercise tests, we observed diaphragmatic fatigue as defined by a significant decline in Pdi,tw from pre- to post-exercise when CMS was applied (Similovski et al. 1989; Mador et al. 2000, 2002). The finding that the post-exercise percentage fall in Pdi,tw was higher after the normoxaemic test (Fig. 7B) suggests that arterial hypoxaemia per se is not a dominant factor in diaphragmatic fatigue, at least at the moderate level (Dempsey & Wagner, 1999) of arterial oxygen saturation tested (92 ± 1%) in the present study. At more severe levels of arterial hypoxaemia (83 ± 1%), diaphragmatic force-generating capacity has been shown to be more impaired during cycling at high altitude compared to equivalent work rates at sea level (Gudjonsdottir et al. 2001). The greater diaphragmatic fatigue observed by Gudjonsdottir et al. (2001) compared to the present study might therefore be attributed to the lower percentage Sa,O2 values attained in that study, resulting from the more severe hypoxic stimulus. Our conclusions should therefore be limited to conditions naturally causing desaturation to no greater a degree than seen in our study. We purposefully sought to investigate the effect of moderate arterial hypoxaemia, as the majority of endurance athletes who develop EIAH (Powers et al. 1988; Dempsey & Wagner, 1999; Nielsen et al. 2002) typically exhibit saturation values in the range seen in the present study (87–93%). Thus, our results seem appropriate to real-world conditions at sea level.
Effect of leg work rate on diaphragmatic fatigue
Our finding that the percentage drop in Pdi,tw was significantly greater following the HI than the LO tests is in line with the results of Johnson et al. 1993), showing that in healthy subjects with a variety of fitness levels, the higher the relative exercise intensity and percentage of 
sustained during exercise, the greater the amount of work done by the diaphragm and the degree of diaphragmatic fatigue determined following exercise. However, in the work of Johnson et al. (1993), respiratory muscle load was higher the higher the power output. In the present study, respiratory effort throughout exercise was designed not to be greater in the high- than in the low-work rate tests. Our findings lead us to hypothesize that the higher degree of diaphragmatic fatigue following the higher leg work rate normoxaemic tests should be attributed to factors governing its blood flow (Babcock et al. 2002). It is reasonable to speculate that diaphragm blood flow would be compromised more during the high-leg-work rate tests, as the greater recruitment of the leg musculature presumably required a greater share of an already maximal cardiac output compared to the low leg work rate tests. Recent work by Mortensen et al. (2005) demonstrated that during incremental cycling, cardiac output increases linearly to 80% of peak power and then plateaus, whereas during constant-load cycling sustained at 85% of peak power, cardiac output reaches maximal values within 5 min. The notion of attainment of maximal cardiac output in both HI and LO tests is also supported by the finding that maximal cardiac output was similar between mild hypoxaemic (16%FI,O2) and normoxaemic exercise conditions in fit subjects performing two-leg knee extension exercise, while the lower oxygen delivery in hypoxaemia led to lower whole-body oxygen uptake (Koskolou et al. 1997). Similarly, during maximal cycling under hyperoxia compared to normoxia, maximal cardiac output (Peltonen et al. 2001) has been reported not to differ, whereas oxygen delivery to the muscles was higher in hyperoxia leading to higher 
(Knight et al. 1993). In the present study 
was indeed significantly higher in the normoxaemic high-leg-work rate tests than in the hypoxaemic lower-leg-work rate tests, possibly because of the greater oxygen delivery (Knight et al. 1993; Koskolou et al. 1997) and leg blood flow (Mortensen et al. 2005). However, whole-body 
reached near maximal values in both normoxaemic and hypoxaemic tests (103 and 94%
, respectively). Therefore, assuming that cardiac output was maximal and not different in the two tests, as implied by the similar heart rates, we reasoned that during the higher work rate normoxaemic tests, the locomotor muscles which in that condition produced higher work output, received a greater share of blood flow at the expense of other metabolically active tissues, including the respiratory muscles. Therefore, even if Pdi was similar, diaphragmatic blood flow was presumably decreased at the high-work-rate tests as the locomotor muscles would require more blood (Mortensen et al. 2005). Hence, one would expect a greater degree of diaphragmatic fatigue in the latter case due to a greater degree of competition for the available blood flow.
Further support for the hypothesis that blood flow limitation and not hypoxaemia is more important to developing diaphragmatic fatigue comes from the work of Harms et al. (1998, 2000) establishing a link between the amount of respiratory muscle work and limb blood flow at maximal levels of exercise. According to these investigators, increasing the amount of respiratory muscle work at maximal exercise significantly reduces leg blood flow and 
, and increases leg vascular resistance, whereas a decrease in the amount of respiratory work increases blood flow and 
and decreases vascular resistance. This has been attributed to an increased muscle sympathetic nerve activity and reflex vasoconstriction with respiratory muscle loading, and vice versa. According to Harms et al. (2000), these changes in sympathetic outflow are mediated by a muscle chemoreflex mechanism known to originate from type III and IV afferents in contracting muscles (Pickar et al. 1994) and in the diaphragm (Hussain et al. 1991). Accordingly, if such a regulatory reflex mechanism underlies the distribution of blood flow between the respiratory and locomotor muscles (Rowell & Cleary, 1990), keeping respiratory muscle work similar while increasing the work output by the legs, as occurred in the present study, could possibly evoke the same regulatory mechanism, but in the opposite direction. Therefore, the greater degree of diaphragmatic fatigue observed at the higher-leg-work rate in the present study could be the result of compromised blood flow to the respiratory muscles (Savard et al. 1989; Wetter et al. 1999; Harms et al. 2000).
Effect of metabolic by products on diaphragmatic fatigue
Acidosis and/or accumulation of metabolic byproducts, such as lactate, in the active musculature have been proposed as possible contributors to diaphragm fatigue (Fitzgerald et al. 1984; Fregosi & Dempsey, 1986; Babcock et al. 1995a). Previous work by Fregosi & Dempsey (1986) has shown that muscle lactate content in the diaphragm increases as blood lactate concentration increases after whole-body normoxic exercise, suggesting that the diaphragm may become progressively acidic, thus contributing to fatigue. In the present study, arterial lactate and pH were not significantly different between the two tests and therefore the difference found in diaphragmatic fatigue is unlikely to be due to either of the two factors. This is also confirmed by the lack of a significant correlation between the difference in post-exercise arterial pH measured 10 min into recovery after the HI and LO tests, and the difference in the reduction in Pdi,tw recorded at the 10th minute of recovery following the HI and LO tests.
Potential limitations of the study
Performing both 5 min exercise tests on the same day could have presented a limitation to the present study. However, the complexity of the experiment and the invasive techniques employed prevented us from testing the subjects on separate days. This is the reason why we performed the tests in a balanced ordering sequence to assure equal numbers of either load application sequence. In addition, the time length of the tests was designed to be the maximal sustainable in order to achieve high work rates and maximal values for 
and cardiac output in our fit subjects (Wagner, 2000; Mortensen et al. 2005). Moreover in fit subjects who are susceptible to EIAH, an exercise test lasting 4–5 min has been reported by Dempsey & Wagner (1999) to be the ideal duration of exercise for the phenomenon of arterial hypoxaemia to be more profound.
Furthermore, we allowed a 90 min period for recovery between the two tests because in the paper by Johnson et al. (1993), the Pdi,tw values had recovered almost completely by an average time of 70 min in subjects exercising in normoxic conditions, while in the study of Babcock et al. (1995a)Pdi,tw had recovered by approximately 90 min following hypoxic exercise. It should be noted that by the 60th minute into recovery, pH and arterial lactate as well as, oxygen uptake and heart rate had returned to pre-exercise levels. It is therefore likely that restoration of blood flow and energy supplies during recovery, as well as removal of lactate from the circulation may explain the quick recovery of Pdi,tw in our study. Indeed, Pdi,tw had completely returned to baseline 60 min after the first test, therefore allowing the absolute value of Pdi,tw at the beginning of the second test to be at an identical level to that before the first test. Nevertheless, because we could not ensure that the diaphragm would be truly ‘back to normal’ but only that Pdi,tw would return to baseline after a 90 min period of rest, we applied a balanced allocation of the trials in our crossover protocol design in order to take into account the possible long-lasting (but not revealed by Pdi,tw measurement) effects of diaphragmatic fatigue.
To determine the degree of diaphragmatic fatigue in the present study we assessed post-exercise changes from baseline in Pdi,tw using CMS of the phrenic nerves. Although this technique coactivates extra-diaphragmatic musculature, it is well tolerated and compares favourably to bilateral phrenic nerve stimulation (BPNS) in terms of assessing diaphragmatic contractility and detecting diaphragmatic fatigue (Hamnegard et al. 1996; Mador et al. 2002; Man et al. 2004). Even though Pdi,tw is larger with CMS compared with BPNS, CMS is technically easier to perform, requiring fewer trial stimulations to confirm supramaximality (Man et al. 2004), which we thought would be advantageous for this study, in which comparative measurements had to be performed repeatedly at precise time intervals in highly trained athletes undergoing two exercise protocols on the same day. Furthermore, although we did not measure diaphragmatic EMG activity, but as in other studies (Hamnegard et al. 1996; Polkey et al. 1998; Mador et al. 2000; Mador et al. 2002) we relied only on Pdi,tw measurements to reproduce consistent CMS, the within-trial coefficient of variation in Pdi,tw assessed at the 10th minute of recovery after the HI and LO tests was 7.1 ± 1.2 0 and 5.3 ± 1.0, respectively, suggesting reasonably consistent stimulation from one series of measurements to another. This figure is in agreement with other reproducibility studies utilizing the same technique that showed that the within-occasion variability ranges between 5 and 8% (Mills et al. 1995, 1996; Mador et al. 2000, 2002).
Significance of EIAH on diaphragm fatigue in highly trained athletes
Our findings provide new insights into the functional effects of EIAH in highly trained endurance athletes. First, we have been able to quantify diaphragmatic fatigue induced by high-intensity (>90%
) normoxic exercise naturally causing moderate levels of arterial desaturation in this highly trained population. Interestingly, the degree of diaphragmatic fatigue in these elite athletes was within the range previously reported for healthy humans with a variety of fitness levels (Johnson et al. 1993, 1996), hence suggesting that EIAH does not exacerbate diaphragm fatigue in these athletes. Second, by preventing EIAH, we showed that the effect of work rate on diaphragm fatigue was greater than that of hypoxaemia, at least at the level of Sa,O2 tested. Hence, when leg work energy requirements are near maximal, blood flow to the diaphragm and not its O2 delivery per se, is more important in causing diaphragmatic fatigue in exceptionally fit athletes. The latter suggestion is in line with studies (Nielsen et al. 1998, 1999, 2002) that showed that there is not a significant effect of EIAH on muscle O2 delivery and that when hyperoxia restores arterial desaturation during exercise, muscle oxygenation is not different from that during exercise in normoxia.
In conclusion, the difference found in diaphragmatic fatigue between normoxaemia (at higher leg work rate) and hypoxaemia (at lower leg work rate) suggests that neither arterial hypoxaemia nor lactic acidosis are likely predominant causative factors in diaphragmatic fatigue in this population, at least at the level of Sa,O2 tested. Rather, this result leads us to hypothesize that blood flow competition with the legs is an important contributor to diaphragmatic fatigue in heavy exercise, assuming that higher leg work required greater blood flow.
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References |
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TopAbstractIntroductionMethodsResultsDiscussionReferences |
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Babcock MA, Pegelow DF, Harms CA & Dempsey JA (2002). Effects of respiratory muscle unloading on exercise-induced diaphragmatic fatigue. J Appl Physiol 93, 201–206.
Babcock MA, Pegelow DF, Johnson BD & Dempsey JA (1996). Aerobic fitness effects on exercise-induced low-frequency diaphragm fatigue. J Appl Physiol 81 (5), 2156–2164.
Babcock MA, Pegelow DF, McClaran SA, Suman OE & Dempsey JA (1995b). Contribution of diaphragmatic work to exercise-induced diaphragm fatigue. J Appl Physiol 78, 1710–1717.
Cibella F, Cuttitta G, Kayser B, Narici M, Romano S & Saibene F (1996). Respiratory mechanics during exhaustive submaximal exercise at high altitude in healthy humans. J Physiol 494 3, 881–890.
Dempsey JA & Wagner PD (1999). Exercise-induced arterial hypoxemia. J Appl Physiol 87, 1997–2006.
Fitzgerald RS, Hauer MX, Bierkamper GG & Raff H (1984). Responses of in vitro rat diaphragm to changes in acid base environment. J Appl Physiol 57, 1202–1210.
Fregosi RF & Dempsey JA (1986). Effects of exercise in normoxia and acute hypoxia on respiratory muscle metabolites. J Appl Physiol 60, 1274–1283.
Gudjonsdottir M, Appending L, Baderna P, Purro A, Patessio A, Vilianis G et al. (2001). Diaphragm fatigue during exercise at high altitude: the role of hypoxia and workload. Eur Respir J 17, 674–680.
Hamnegard CH, Wragg S, Kyroussis D, Mills GH, Polkey MI, Moran J et al. (1996). Diaphragm fatigue following maximal ventilation in man. Eur Respir J 9, 214–224.
Harms CA, Thomas A, Wetter J, McClaran SR, Pegelow DF, Nickele GA et al. (1998). Effects of respiratory muscle work on cardiac output and its distribution during maximal exercise. J Appl Physiol 85, 609–618.
Harms GA, Wetter TJ, Croix CM, Pegelow DF & Dempsey JA (2000). Effects of respiratory muscle work on exercise performance. J Appl Physiol 89, 131–138.
Hussain S, Chatillon A, Comtois A, Roussos C & Magder S (1991). Chemical activation of thin fiber phrenic afferents II. Cardiovascular responses. J Appl Physiol 70, 77–86.
Johnson BD, Aaron EA, Babcock MA & Dempsey JA (1996). Respiratory muscle fatigue during exercise: implications for performance. Med Sci Sports Exerc 28, 1129–1137.
Johnson BD, Babcock MA, Suman OE & Dempsey JA (1993). Exercise-induced diaphragmatic fatigue in healthy humans. J Physiol 460, 385–405.
Knight DR, Schaffartzik W, Poole DC, Hogan MC, Bebout DE & Wagner PD (1993). Effects of hyperoxia on maximal leg O2 supply and utilization in men. J Appl Physiol 75, 2586–2594.
Koskolou MD, Calbet JAL, Radegran CG & Roach RC (1997). Hypoxia and the cardiovascular response to dynamic knee-extensor exercise. Am J Physiol 272, H2655–H2663.[Medline]
Laird NM & Ware JH (1982). Random effect models for longitudinal data. Biometrics 38, 963–974.[CrossRef][Medline]
Mador MJ, Khan S & Kufel TJ (2002). Bilateral anterolateral magnetic stimulation of the phrenic nerves can detect diaphragmatic fatigue. Chest 121, 452–458.
Mador MJ, Kufel TJ, Pineda LA & Sharma GK (2000). Diaphragmatic fatigue and high-intensity exercise in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 161, 118–123.
Man WDC, Moxham J & Polkey MI (2004). Magnetic stimulation for the measurement of respiratory and skeletal muscle function. Eur Respir J 24, 846–860.
Mills GH, Kyrousis D, Carl H, Hamnegard CH, Polkey MI, Green M et al. (1996). Bilateral magnetic stimulation of the phrenic nerves from an anterolateral approach. Am J Respir Crit Care Med 154, 1099–1105.[Abstract]
Mills GH, Kyrousis D, Hamnegard CH, Wragg S, Moxham J & Green M (1995). Unilateral magnetic stimulation of the phrenic nerve. Thorax 50, 1162–1172.[Abstract]
Mortensen SP, Dawson EA, Yoshiga CC, Dalsgaard MK, Damsgaard R, Secher NH et al. (2005). Limitations to systemic and locomotor limb muscle oxygen delivery and uptake during maximal exercise in humans. J Physiol 566, 273–285.
Nielsen HB, Boushel R, Madsen P & Secher NH (1999). Cerebral desaturation during exercise reversed by O2 supplementation. Am J Physiol Heart Circ Physiol 277, H1045–H1052.
Nielsen HB, Bredmose PP, Stromstad M, Volianitis S, Quistorff B & Secher NH (2002). Bicarbonate attenuates arterial desaturation during exercise in humans. J Appl Physiol 93, 724–731.
Nielsen HB, Madsen P, Svedsen LB, Roach RC & Secher NH (1998). The influence of PaO2, pH and Sa,O2 on maximal oxygen uptake. Acta Physiol Scand 164, 89–97.[CrossRef][Medline]
Peltonen JE, Tikkanen HO & Rusko HK (2001). Cardiorespiratory responses to exercise in acute hypoxia, hyperoxia and normoxia. Eur J Appl Physiol 85, 82–88.[CrossRef][Medline]
Pickar JG, Hill JR & Kaufman MP (1994). Dynamic exercise stimulates group III muscle afferents. J Neurophysiol 71, 753–760.
Polkey MI, Hamnegard CH, Hughes PD, Rafferty GF, Green M & Moxham J (1998). Influence of acute lung volume change on contractile properties of human diaphragm. J Appl Physiol 85, 1322–1328.
Powers SK, Dodd S, Lawler J, Landry G, Kirtley M, McKnight T et al. (1988). Incidence of exercise induced hypoxemia in elite endurance athletes at sea level. Eur J Appl Physiol 58, 298–302.[CrossRef]
Roussos C, Fixley M, Cross D & Macklem PT (1979). Fatigue of inspiratory muscles and their synergetic behavior. J Appl Physiol 46, 879–904.
Rowell LB & Cleary DS (1990). Reflex control of the circulation during exercise: chemoreflexes and mechanoreflexes. J Appl Physiol 69, 407–418.
Savard SM, Richter EA, Strange S, Kiens B, Christensen NJ & Saltin B (1989). Norepinephrine spillover from skeletal muscle during exercise: role of muscle mass. Am J Physiol 26, H1812–H1818.
Similovski T, Fleury B, Launois S, Cathala HP, Bouche P & Derenne JP (1989). Cervical magnetic stimulation: a new painless method for bilateral phrenic stimulation in conscious humans. J Appl Physiol 67, 1311–1318.
Wagner PD (2000). Reduced maximal cardiac output at altitude; mechanisms and significance. Respir Physiol 120, 1–11.[CrossRef][Medline]
Wetter TJ, Harms CA, Nelson WB, Pegelow DF & Dempsey JA (1999). Influence of respiratory muscle work on [Reinsert]o2 and leg blood flow during submaximal exercise. J Appl Physiol 87, 643–651.
Wragg S, Hamnegard C, Road J, Kyroussis D, Moran J, Green M et al. (1994). Potentiation of diaphragmatic twitch after voluntary contraction in normal subjects. Thorax 49, 1234–1237.[Abstract]
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; B), and heart rate (HR; C) throughout the low (80% WRmax (
)) and high (90% WRmax (•)) work rate tests. Values are means ±S.E.M. for 10 subjects. *Significant differences between the two conditions, P < 0.05.
; A), tidal volume (VT; B) and breathing frequency (f; C) throughout the low (80% WRmax (
) and second (
) exercise tests; B, the high (90% WRmax (•)) and low (80% WRmax (
significant difference from baseline P < 0.05.