AJP - Regu Fuel your research with LabChart
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Am J Physiol Regul Integr Comp Physiol 292: R1279-R1286, 2007. First published November 22, 2006; doi:10.1152/ajpregu.00554.2006
0363-6119/07 $8.00
This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
292/3/R1279    most recent
00554.2006v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via ISI Web of Science (5)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Katayama, K.
Right arrow Articles by Dempsey, J. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Katayama, K.
Right arrow Articles by Dempsey, J. A.

ENVIRONMENTAL, EXERCISE AND RESPIRATORY PHYSIOLOGY

Effect of arterial oxygenation on quadriceps fatigability during isolated muscle exercise

Keisho Katayama,1,2 Markus Amann,1 David F. Pegelow,1 Anthony J. Jacques,1 and Jerome A. Dempsey1

1The John Rankin Laboratory of Pulmonary Medicine, Department of Health, Population Health Sciences, University of Wisconsin-Madison, Wisconsin; and 2Research Center of Health, Physical Fitness and Sports, Nagoya University, Nagoya, Japan

Submitted 3 August 2006 ; accepted in final form 15 November 2006


   ABSTRACT
TOP
 ABSTRACT
METHODS
 RESULTS
 DISCUSSION
 GRANTS
 REFERENCES
 
The effect of various levels of oxygenation on quadriceps muscle fatigability during isolated muscle exercise was assessed in six male subjects. Twitch force (Qtw) was assessed using supramaximal magnetic femoral nerve stimulation. In experiment 1, maximal voluntary contraction (MVC) and Qtw of resting quadriceps muscle were measured in normoxia [inspired O2 fraction (FIO2) = 0.21, percent arterial O2 saturation (SpFormula) = 98.4%, estimated arterial O2 content (CaO2) = 20.8 ml/dl], acute hypoxia (FIO2 = 0.11, SpFormula = 74.6%, CaO2 = 15.7 ml/dl), and acute hyperoxia (FIO2 = 1.0, SpFormula = 100%, CaO2 = 22.6 ml/dl). No significant differences were found for MVC and Qtw among the three FIO2 levels. In experiment 2, the subjects performed three sets of nine, intermittent, isometric, unilateral, submaximal quadriceps contractions (62% MVC followed by 1 MVC in each set) while breathing each FIO2. Qtw was assessed before and after exercise, and myoelectrical activity of the vastus lateralis was obtained during exercise. The percent reduction of twitch force (potentiated Qtw) in hypoxia (–27.0%) was significantly (P < 0.05) greater than in normoxia (–21.4%) and hyperoxia (–19.9%), as were the changes in intratwitch measures of contractile properties. The increase in integrated electromyogram over the course of the nine contractions in hypoxia (15.4%) was higher (P < 0.05) than in normoxia (7.2%) or hyperoxia (6.7%). These results demonstrate that quadriceps muscle fatigability during isolated muscle exercise is exacerbated in acute hypoxia, and these effects are independent of the relative exercise intensity.

hypoxia; magnetic femoral nerve stimulation; hyperoxia; hypoxemia; quadriceps twitch force

WE AND OTHERS HAVE RECENTLY SHOWN that high-intensity whole body exercise to exhaustion caused significant peripheral limb muscle fatigue and that the level of arterial O2 content (CaO2) via changes in inspired O2 fraction (FIO2) is a significant determinant of the rate at which peripheral muscle fatigue is developed during exercise (2, 43, 46). In these studies, evidence for the effects of CaO2 on peripheral fatigue was obtained via measures of quadriceps force output using supramaximal magnetic stimulation obtained pre- vs. postexercise and also by the rate of rise of quadriceps muscle electromyogram (EMG) during the exercise. The latter measurement presumably indicates the rate of motor unit recruitment in response to peripheral fatigue development (2, 46). Given that a changing CaO2 induced by breathing various FIO2 also had significant effects on maximal peak exercise capacity during whole body exercise, the observed effect of changing CaO2 on peripheral limb fatigue might be attributed at least in part to changes in relative work intensity (2, 43). Different relative work intensities might be expected to influence the rate of accumulation of muscle metabolites (27) and therefore influence peripheral muscle fatigue.

We tested this hypothesis by using isolated submaximal isometric contractions of the quadriceps muscle, since maximal force output of locomotor muscle under baseline resting conditions is not affected by breathing various FIO2 levels (0.110–0.123, equivalent to an altitude of 4,000–5,050 m) (11, 21, 22, 39, 48). Accordingly, repeated quadriceps muscle contractions at the same absolute force output with variations in FIO2 would also be carried out at the same relative work intensity. Previous reports differ in findings concerning hypoxic effects on muscle force output during isolated muscle exercise (5, 6, 17, 21), although these studies have only used measures of voluntary contractions. We utilized the quadriceps twitch force output in response to supramaximal magnetic femoral nerve stimulation (29, 42) as a quantitative estimate of the degree of contractile peripheral fatigue elicited by isolated muscle exercise (33). This measurement was used before and after isolated intermittent isometric exercise of the quadriceps muscle under varying conditions of FIO2, ranging from hypoxia to hyperoxia. We also measured integrated EMG for each contraction and used its rate of change throughout each exercise set as an index of the rate of motor unit recruitment (18).


   METHODS
TOP
 ABSTRACT
 METHODS
RESULTS
 DISCUSSION
 GRANTS
 REFERENCES
 
Subjects

Six healthy trained male cyclists volunteered for this study (age 20.8 ± 1.0 yr, height 178.1 ± 1.9 cm, body mass 71.2 ± 4.0 kg). The subjects were informed about the experimental procedures and potential risks involved in this study, and their written consent was obtained. All procedures were approved by the Institutional Review Board of the University of Wisconsin at Madison. During a preliminary visit to the laboratory, subjects were familiarized with the equipment and procedures.

Magnetic Femoral Nerve Stimulation

Quadriceps twitch forces (Qtw) were evoked via supramaximal magnetic femoral nerve stimulation (Magstim 200; Jail Medical, Newton, MA) with a 70-mm figure-of-eight coil (33). A detailed description of the procedures can be found elsewhere (1, 2, 43, 44). Briefly, subjects lay semisupine on a table with the right thigh resting in a preformed holder and the knee joint angle set at 1.57 rads (90°) of flexion. A noncompliant strap, which was connected to a load cell (Interface, model SM 1000; Scottsdale, AZ), was attached around the subject's right leg just superior to the malleoli of the ankle joint. A plateau in baseline Qtw and compound action potential (M wave) amplitudes with increasing stimulus intensities was confirmed in all subjects by using the progressive increase in power output, indicating maximal depolarization of the femoral nerve (1, 2, 43, 44).

The stimulator power output was set to 100% during all subsequent testing procedures. First, eight single stimuli, separated by 30 s, were given to determine unpotentiated quadriceps twitch force (Qtw,unp). The use of potentiated quadriceps twitch force (Qtw,pot) to assess peripheral fatigue eliminates the confounding contributions of contractile history of a muscle, especially following exercise bouts of varying duration and intensity. Changes in Qtw,pot also have been shown to be more sensitive for detecting fatigue compared with Qtw,unp (29, 32). Accordingly, we measured Qtw 5 s after a 5-s maximal voluntary contraction (MVC) of the quadriceps, obtaining a total of six Qtw,pot values (1, 2, 43, 44). Previous studies showed that the degree of potentiation was slightly smaller after the first and, to a lesser extent, after the second MVC (1, 2, 29, 43, 44). In this study, we found that Qtw,pot after the third MVC was also slightly smaller than the last three Qtw,pot values, thus we discarded the first three measurements. Voluntary activation of the quadriceps during the MVC, i.e., %voluntary activation, was assessed using a superimposed twitch technique (36). Briefly, the force produced during a superimposed single twitch on the MVC was compared with the force produced by the potentiated single twitch delivered 5 s afterward (2, 33). The entire assessment procedure took ~8 min. Within-twitch variables included maximal rate of force development (MRFD), maximal rate of relaxation (MRR), contraction time (CT), and one-half relaxation time (RT0.5) measured in response to Qtw,unp and Qtw,pot (1, 2, 45). Each variable is presented as the mean of eight Qtw,unp and three Qtw,pot values.

Reproducibility

Subjects were tested for between-day reliability by repeating the magnetic stimulation protocol at rest on separate visits to the laboratory. There was no systematic bias in the baseline measurements between days. Between-day coefficients of variation were 5.8% (range 1.9–10.9%) for MVC, 2.2% (range 0.0–3.5%) for %voluntary activation, 3.9% (range 2.2–8.4%) for Qtw,pot, 3.5% (range 0.4–9.1%) for Qtw,unp, and 4.0% (range 0.5–9.9%) for contractile properties (mean for MRFD, MRR, CT, and RT0.5).

Myoelectrical Activity

A detailed description of the exact procedures is given elsewhere (1, 2). Briefly, quadriceps EMG was recorded from the right vastus lateralis (VL), vastus medialis (VM), and rectus femoris (RF) by using monitoring electrodes with full-surface solid adhesive hydrogel (Kendall H59P; Mansfield, MA). We used on-site amplification and filtering with a Butterworth band-pass filter (BMA-830; CWE, Ardmore, PA) with a low-pass cutoff frequency of 10 Hz and a high-pass cutoff frequency of 1 kHz. Surface electrodes were used to record 1) magnetically evoked compound mass action potentials (M wave) for VL, VM, and RF to evaluate pre- to postexercise changes in membrane excitability and 2) EMG of VL during exercise to estimate changes in motor unit recruitment. To evaluate changes in M-wave properties, we obtained peak amplitude, duration, conduction time, and area (1, 2, 45). Raw EMG signals (VL) for each muscle contraction during experiment 2 were recorded for later analysis of integrated EMG (iEMG) via a computer algorithm [for details, see Amann et al. (1, 2)].

Cardiorespiratory Measurements

The subjects breathed through a face mask (8930; HansRudolph, Kansas, MO) connected to a one-way valve (2700; HansRudolph) throughout the experiment. Respiratory variables were measured breath by breath and averaged over a 60-s sampling interval. Heart rate (HR) was measured from the R-R interval of an electrocardiogram by using a three-lead arrangement. Arterial O2 saturation (SpFormula was estimated using a pulse oximeter with optodes placed on the forehead (Nellcor OxiMax, Pleasanton, CA) (43). CaO2 was estimated assuming a Hb concentration of 15.0 g/dl and an alveolar [estimated via an end-tidal partial pressure of O2 (PETO2)]-arterial O2 difference at 10 mmHg; CaO2 (ml/dl) = [15.0 x 1.39 x SpFormula/100] + [(PETO2 – 10) x 0.003].

Experimental Protocol

The time course of the experimental design is presented in Fig. 1. Experiment 1 was aimed at evaluating the effects of various FIO2/SpFormula values on muscle functions in the subjects at rest. Subjects reported to the laboratory on three different occasions, separated by 72 h. In random order, resting quadriceps muscle function was measured while subjects breathed a normoxic (FIO2 0.21), hypoxic (FIO2 0.10 to 0.11), or hyperoxic (FIO2 1.0) humidified gas mixture. FIO2 during the hypoxic trial was individually adjusted to induce a SpFormula of 75%. The participants, blinded to the FIO2, were exposed to the respective gas mixtures 10 min before each assessment procedure.


Figure 1
View larger version (12K):
[in this window]
[in a new window]

  		Fig. 1. Experimental design. In experiment 1, resting quadriceps muscle function was measured while subjects breathed a normoxic, hypoxic, or hyperoxic gas mixture. In experiment 2, the subjects performed 3 sets of 9 intermittent, isometric, submaximal quadriceps contractions while breathing each FIO2. We measured maximal voluntary contraction (MVC) and potentiated quadriceps twitch force (Qtw) immediately after each set of contractions. Before exercise (Pre) and 10 min after (Post) all 3 sets of contractions were completed, we measured unpotentiated Qtw, MVC, and potentiated Qtw.

 
Experiment 2 was aimed at evaluating the effects of various FIO2/SpFormula values on the rate of development of peripheral quadriceps fatigue. Before the first visit of experiment 2, subjects' individual submaximal target force output was determined (in hypoxia) to ensure that the subjects were able to complete the fatigue protocol. The same subjects reported to the laboratory on three additional occasions, separated by 96 h, to perform the identical protocol of intermittent isometric contractions of the right quadriceps while being exposed to one of the aforementioned FIO2 conditions. To determine exercise-induced peripheral quadriceps fatigue, we assessed muscle function before (Pre) and after fatigue exercise (Post) while subjects breathed room air. Since it is known that the subsequent twitches are significantly increased in magnitude after vigorous voluntary contractions (35), assessment of muscle function was performed at 10 min after exercise (33, 34) (Fig. 1).

Fatigue Protocol (Experiment 2)

Subjects were in semisupine position with the knee joint angle set at 90° of flexion and arms folded across the chest throughout the fatigue protocol. Three sets of nine submaximal isometric quadriceps contractions (target force 62.0 ± 3.7% of MVC, range 47–75% of MVC) followed by one MVC maneuver were performed; each contraction was held for 5 s followed by a 5-s relaxation period (a total of 10 in each set). To evaluate %voluntary activation during MVC, we obtained twitches during (superimposed twitch) and 5 s after the MVC (Qtw,pot) in each set. The three sets were separated by a 1.5-min rest period. Subjects received continuous visual (personal computer monitor) and verbal feedback to ensure maintenance of target force output and the correct rhythm. The fatigue protocol was repeated at the same absolute exercise intensity in all three FIO2 conditions.

Statistical Analysis

Values are expressed as means ± SE. The comparison of parameters between various FIO2 levels (normoxia, hypoxia, and hyperoxia) was achieved using one-way analysis of variance (ANOVA) and a Tukey-Kramer test. The changes in each parameter during fatigue exercise were analyzed using one-way ANOVA with repeated measurements and a Newman-Keuls test. The level of significance was set at P < 0.05.


   RESULTS
TOP
 ABSTRACT
 METHODS
 RESULTS
DISCUSSION
 GRANTS
 REFERENCES
 
Effects of Different Levels of Oxygenation on Resting Quadriceps Muscle Function (Experiment 1)

Cardiorespiratory parameters. Resting cardiorespiratory parameters in normoxia, hypoxia, and hyperoxia are shown in Table 1. In hypoxia, minute ventilation and HR were higher (P < 0.05) and PETO2 and end-tidal partial pressure of CO2 (PETCO2), SpFormula, and estimated CaO2 were lower (P < 0.05) compared with those in normoxia and hyperoxia. PETO2 and CaO2 in hyperoxia were higher (P < 0.05) than those in normoxia.


View this table:
[in this window]
[in a new window]

  		Table 1. Cardiorespiratory parameters at rest (experiment 1)

 
Muscle function. Resting MVC, %voluntary activation, twitch force, and within-twitch variables among different levels of oxygen are shown in Table 2. There were no differences in these measures among normoxia, hypoxia, and hyperoxia under baseline resting conditions.


View this table:
[in this window]
[in a new window]

  		Table 2. Effect of various levels of oxygenation on muscle function at rest (experiment 1)

 
These findings confirm earlier reports (see Introduction). Thus, since changes in FIO2 and CaO2, per se, had no effect on maximal quadriceps contractility under preexercise resting conditions, repeated quadriceps contractions performed at the same absolute work rate were conducted at the same relative exercise intensity (experiment 1 below).

Effects of Different Levels of Oxygenation on Quadriceps Muscle Fatigability (Experiment 2)

Force output and iEMG during fatigue exercise. There were no significant differences in force output (from first to ninth submaximal contractions in each set) during fatigue exercise protocols among the three FIO2 conditions. Figure 2A shows a representative example of the change in iEMG of vastus lateralis muscle with increasing number of contractions during fatiguing exercise. Note the progressive increase in iEMG during each of the three sets of contractions.


Figure 2
View larger version (22K):
[in this window]
[in a new window]

  		Fig. 2. A: typical example of the changes in vastus lateralis integrated electromyogram (iEMG) during fatiguing exercise in hypoxia. The numbers (1–9) within each set refer to each 5-s isometric contraction performed at a constant work load. B: group mean iEMG values for all conditions (expressed as a percentage of the initial 3 contractions). There were no significant differences in absolute power output or %MVC among the 3 conditions [477.4 ± 32.8 N and 64.1 ± 4.4% in normoxia (NORM), 447.4 ± 32.3 N and 64.5 ± 4.7% in hypoxia (HYPO), and 447.0 ± 32.1 N and 64.8 ± 4.9% in hyperoxia (HYPER)]. Values are means ± SE; n = 6. *P < 0.05, HYPO vs. NORM and HYPER.

 
Figure 2B demonstrates the group mean percent changes in iEMG during the fatiguing exercise protocol among conditions of normoxia, hypoxia, and hyperoxia. Data were normalized to the mean of the first three contractions during the first set. The percent increase in iEMG in hypoxia was significantly (P < 0.05) greater than that in normoxia or hyperoxia at the latter half of the first set and also during the second and third sets of exercise (15.4 ± 1.3% in hypoxia, 7.2 ± 1.7% in normoxia, and 6.7 ± 1.1% in hyperoxia, from the initial three contractions in the first set to final contraction in the third set). There was no significant difference in the increase in iEMG between normoxia and hyperoxia throughout fatiguing exercise.

M wave. Table 3 shows the changes in M-wave properties after the fatiguing exercise protocol in normoxic, hypoxic, and hyperoxic conditions. No significant effects of exercise or FIO2 were found for any of the M-wave properties.


View this table:
[in this window]
[in a new window]

  		Table 3. Changes in twitch force, M-wave, and contractile properties after fatigue exercise protocol (experiment 2)

 
Twitch force. Qtw,pot decreased progressively (P < 0.05) after each set in normoxic, hypoxic, and hyperoxic conditions (Fig. 3). The reduction of Qtw,pot during and after exercise in hypoxia was significantly (P < 0.05) greater than in normoxia and hyperoxia, but there was no difference in the changes in Qtw,pot between normoxia and hyperoxia (Fig. 3 and Table 3). Similarly, Qtw,unp decreased significantly (P < 0.05) following fatigue exercise in all three conditions, and the percent reduction of Qtw,unp in hypoxia was significantly (P < 0.05) greater than in normoxia and hyperoxia (Table 3).


Figure 3
View larger version (12K):
[in this window]
[in a new window]

  		Fig. 3. Changes in potentiated Qtw (Qtw,pot) during fatigue exercise protocol. Qtw,pot during fatigue exercise was obtained 5 s after MVC in each set. Post refers to 10 min after the third set of repeated isometric contractions (also see Fig. 1). Values are means ± SE; n = 6. *P < 0.05, HYPO vs. NORM and HYPER. {dagger}P < 0.05, HYPO vs. HYPER.

 
Within-twitch variables. The changes in MRFD, MRR, CT, and RT0.5 of the twitch (Qtw,pot and Qtw,unp) following the fatigue exercise protocol also are indicated in Table 3. In each condition, there were significant (P < 0.05) decreases in MRFD and MRR and an increase RT0.5 following the fatigue protocol, whereas no significant changes in CT were observed. The percent decreases in MRFD and MRR and the increase in RT0.5 in hypoxia were significantly (P < 0.05) greater than those in normoxia and hyperoxia. There were no significant differences in the changes in these within-twitch parameters between normoxia and hyperoxia following fatigue exercise.

MVC, iEMG during MVC, and percent voluntary activation. MVC decreased progressively (P < 0.05) following each set (Fig. 4). The reductions in MVC in hypoxia after each set were greater (P < 0.05) than in normoxia or hyperoxia, with no difference between normoxia and hyperoxia. Integrated EMG during MVC after each set of fatiguing exercise fell significantly (P < 0.05) (Table 4), but there were no significant differences in the reductions in iEMG during the MVC among the three conditions of oxygenation. The %voluntary activation did not change during the course of the fatiguing exercise at any FIO2 level.


Figure 4
View larger version (13K):
[in this window]
[in a new window]

  		Fig. 4. Changes in MVC during fatigue exercise protocol. MVC during fatiguing exercise was performed immediately following the 9th contraction in each set. Values are means ± SE. *P < 0.05, HYPO vs. NORM and HYPER. {dagger}P < 0.05, HYPO vs. HYPER.

 

View this table:
[in this window]
[in a new window]

  		Table 4. Changes in iEMG during MVC and %voluntary activation during fatigue exercise protocol (experiment 2)

 

   DISCUSSION
TOP
 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
GRANTS
 REFERENCES
 
Summary of Findings

We confirmed that hypoxia had no effect on maximum quadriceps force development under resting conditions. Next, using repeated isometric submaximal contractions of the isolated quadriceps muscle at the same force output, we determined that hypoxia significantly increased the rate of development of exercise-induced quadriceps fatigue. This effect of hypoxia, compared with normoxia or hyperoxia, was shown with three types of measures of peripheral fatigue: 1) greater reductions in muscle force output following exercise, in response to supramaximal femoral nerve stimulation; 2) increased rate of rise in quadriceps iEMG activity during exercise; and 3) greater effects on intratwitch indexes of contractile properties. Hyperoxia did not influence exercise-induced quadriceps fatigue over that observed in normoxia. These findings provide unique evidence of significant hypoxic effects specifically on peripheral quadriceps fatigue as induced by isolated muscle exercise. Furthermore, they imply that hypoxia contributes to exercise-induced peripheral muscle fatigue independently, at least in part, of its effects on relative exercise intensity.

Hypoxic Effects on Peripheral Muscle Fatigue

Although there is agreement that various levels of FIO2 do not affect maximum contractile force in nonexercising muscle (see Table 2 and Introduction), there is disagreement on the effects of hypoxia on the exercising isolated muscle. By using only volitional measurements of MVC and sustained isometric exercise, a reduction in FIO2 was shown to have no significant influence on rate of fatigue development during isolated muscle exercise (5, 6). However, the increased intramuscular pressure accompanying sustained isometric exercise causes substantial and sustained ischemia, even in normoxia (4, 5). When intermittent isometric exercise of the adductor pollicis muscle was used to cause fatigue, acute hypoxia significantly accelerated the rate of decline of MVC force output (21). These data are similar to our findings in the present study using MVC measurements of quadriceps force output (Fig. 4).

Our study extends previous findings concerning hypoxic effects on fatigue through our measurements of quadriceps twitch force (Qtw,unp and Qtw,pot) and within-twitch variables as an effort-independent method to quantify the exercise-induced peripheral fatigue. Three types of findings are consistent in support of a significant hypoxic effect on the rate of peripheral fatigue development. First, and most important, hypoxia exacerbated the exercise-induced reductions in quadriceps potentiated twitch force. This effect of hypoxia was evident early in the development of fatigue and persisted as exercise continued (Fig. 3). Second, pre- vs. postexercise changes in intratwitch measures of contractile properties (see below and Table 3) also were consistent with a significant effect of hypoxia on exercise-induced peripheral fatigue. Finally, there was additional evidence during the exercise of twofold increases in the rate of rise of integrated quadriceps EMG in hypoxia vs. normoxia or hyperoxia (Fig. 2B), and this effect of hypoxia also was evident during the initial nine contractions and persisted throughout the remainder of the exercise. These findings suggest that additional motor units were recruited during exercise in hypoxia to compensate for progressive failure within the contractile apparatus (18, 46). Furthermore, the greater increase in iEMG during exercise in hypoxia also may reflect changes in fiber- type recruitment. During fatiguing forearm exercise in hypoxia, a shift toward an increased type II fiber recruitment as a direct effect of hypoxia per se has been shown (14). Changes in fiber-type recruitment pattern during whole body exercise also occur due to changes in relative exercise intensity from normoxia to hypoxia. However, relative exercise intensity was not affected in this study dealing with isolated muscle exercise. Increased type II fibers are associated with higher spike amplitudes (24, 38, 46), and this may contribute to the enhanced iEMG observed during hypoxic exercise. Although these measurements of surface EMG are certainly subject to a variety of artifacts (12), we wish to emphasize 1) that EMG measurements were made at equal work rates and durations, with the only consistent difference between trials being a change in FIO2, and 2) the hypoxic effects on increasing EMG coincided with changes in Qtw, with the latter being our most objective and reproducible measurement of peripheral fatigue.

Hypoxic Effects on "Central Fatigue"?

MVC decreased progressively throughout the submaximal exercise, and this reduction was exacerbated by hypoxia. The MVC changes represent the total fatigue incurred by exercise and/or hypoxia, consisting of both peripheral and central components. The major aim of our study was to evaluate hypoxic effects specifically on peripheral muscle fatigue; however, we also assessed the effects of isolated muscle exercise and hypoxia on estimates of central fatigue, through the use of the interpolated twitch (%voluntary activation) and the quadriceps iEMG during the MVC maneuver. Exercise of the isolated quadriceps, per se, (at all FIO2 levels) showed no change in the %voluntary activation measure, which agrees with the findings of Mador et al. (33), but it did result in a small, yet significant 5–9% reduction in the quadriceps iEMG during the postexercise MVC maneuver (Table 4). Neither of these measures was affected further by hypoxia superimposed on the exercise.

Neither of these measures lend themselves to straightforward interpretation in terms of hypoxic or exercise effects on central fatigue, because 1) the EMG measure during the MVC is subject to several types of artifact, including amplitude cancellation (12, 28), which might account for at least some of its reduction in the postexercise period, and 2) the %voluntary activation measure is known to be highly "task specific" (23) so that the measures we obtained during the MVC maneuver following exercise might not pertain to the determinants of performance during the submaximal repetitive contraction protocol. Thus, although we think it is important to report these data on %voluntary activation, we cannot be sure that acute hypoxia had no significant effect on central fatigue during the exercise, in addition to the substantial documented effects on peripheral fatigue (23). For example, with cycling exercise in a time-trial mode in which the subject is free to determine power output on a second-by-second basis, alterations in arterial oxygenation caused significant changes in central motor output (as judged by changes in quadriceps iEMG during the exercise). These changes were closely linked to changes in the rate of development of peripheral muscle fatigue (as assessed by {Delta}Qtw) (1).

Causes of Hypoxia-Induced Changes in Muscle Fatigability During Exercise

The relationship between hypoxia-induced changes in convective O2 transport to the working muscle and altered muscle bioenergetics and rate of metabolite accumulation needs to be considered as a major determinant of the increased level of exercise-induced fatigue found in hypoxia. We now summarize recent findings from the literature that might explain the mechanisms underlying hypoxia-induced peripheral muscle fatigue.

First, compared with exercise at the same intensity in normoxia, increased muscle metabolic acidosis during heavy exercise is likely to occur in hypoxia (27) and, among others, protons have traditionally been suggested to play a major role in metabolic fatigue (8, 13, 19, 31, 37). However, recent in vitro studies have questioned the deleterious role of [H+] in metabolic fatigue (7, 10, 40, 41). Nevertheless, the question regarding the relative contribution of protons to muscle fatigue remains a controversy with contradictory viewpoints (30). An alternative major contributor to metabolic fatigue is inorganic phosphate (Pi) (9, 15, 20, 47). Cytoplasmic Pi is thought to enter the sarcoplasmic reticulum and bind to Ca2+ to form a precipitate (CaPi), thus reducing the amount of releasable Ca2+ that contributes to perturbations of excitation-contraction coupling (15). Of relevance to our findings is the observation that the rate of phosphocreatine (PCr) hydrolysis and concomitant inorganic Pi accumulation is faster in hypoxia and slower in hyperoxia compared with normoxia (25–27). Recapitulating, since O2 supply has been shown to influence the accumulation of Pi, the different rates of Pi aggregation might be the key mechanism explaining the effect of {Delta}CaO2 on the rate of accumulation of fatigue during isolated muscle exercise.

Second, hypoxia per se has been suggested to affect fiber- type contribution by attenuating the sensitivity of type III/IV muscle afferents [their stimulation is associated with a preferential recruitment of O2-dependent type I muscle fibers (3)], thus reducing the recruitment of fatigue resistant type I fibers (14). Consequently, more type II muscle fibers need to be activated under hypoxemic conditions to maintain a constant force output. Since type II fibers are associated with an increased rate of metabolite accumulation and fatigue development, relative to type I fibers (16), the O2-dependent change in fiber type contribution (more type II fibers in hypoxia) might account for at least a portion of the exaggerated peripheral fatigue associated with reduced CaO2.

Relevance to Hypoxic Effects During Whole Body Exercise

As outlined in the Introduction, the hypoxic effects on augmenting the rate of peripheral fatigue development during exercise that we presently observed with an isolated muscle exercise protocol are analogous to what has been previously observed during sustained cycling exercise at high intensity (2, 43, 46). That is, when compared at equal work rates and equal durations of cycle exercise, hypoxia (vs. normoxia) caused 1) a 50% greater reduction in Qtw (pre- to postexercise), 2) significantly greater changes in within-twitch contractile properties, and 3) a twofold greater time-dependent rise in quadriceps iEMG during cycling (2). Since hypoxia decreased the peak work rate and maximum O2 consumption observed during cycling, this means that the constant load cycling exercise was carried out at an elevated relative intensity of exercise, which in turn would be expected to increase the rate of accumulation of fatigue-causing metabolites (27). However, our present findings and those of others (11, 21, 22, 39, 48) show that MVC or force output in response to supramaximal motor nerve stimulation in the rested muscle was not influenced by hypoxia; thus isolated submaximal quadriceps exercise was conducted at equivalent levels of both absolute and relative force outputs. We conclude that a significant portion of hypoxic effects on exercise-induced peripheral fatigue does not require an increase in the relative exercise intensity.

A major difference between our isolated muscle studies and those using whole body exercise (2) was that hyperoxia (vs. normoxia) reduced the rate of fatigue development during cycling exercise but not during the isolated muscle exercise. These hyperoxic (vs. normoxic) effects during cycling were significant but relatively small, comprising less than one-third the magnitude of the effects caused by hypoxia on the change in Qtw, rate of rise of iEMG, and within-twitch measures of muscle contractile properties (2, 43). The comparisons of the two types of exercise are confounded in part by the average 5–7% Hb O2 desaturation experienced during normoxic cycling exercise as opposed to no change in SpFormula (or CaO2) from rest during the isolated muscle exercise. In addition, perhaps the contribution of a reduction in relative exercise intensity with hyperoxia provided a greater contribution to relieving the rate of peripheral fatigue development during whole body exercise than during isolated muscle exercise.

In conclusion, the reduction in twitch force, rate of rise of iEMG, and alteration in contractile properties of locomotor muscle during intermittent isometric quadriceps muscle exercise in hypoxia were larger than those in normoxia or hyperoxia. These results suggest that quadriceps muscle fatigability is exaggerated during isolated muscle exercise in acute hypoxia, and this effect is, at least in part, independent of the relative exercise intensity.


   GRANTS
TOP
 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
 GRANTS
REFERENCES
 
This study was supported by National Heart, Lung, and Blood Institute Grant HL 15469-34 and the American Heart Association.


   ACKNOWLEDGMENTS
 
We appreciate the cooperation of the subjects in the present study, and we also extend thanks to members of the John Rankin Laboratory of Pulmonary Medicine, University of Wisconsin (Madison, WI). We also thank Dr. M. Shinohara (University of Colorado, Boulder, CO) and Dr. Y. Yoshitake (Oita University of Nursing and Health Sciences, Oita-Ken, Japan) for informative discussions of electromyographic data.


   FOOTNOTES
 

Address for reprint requests and other correspondence: K. Katayama, The John Rankin Laboratory of Pulmonary Medicine, Univ. of Wisconsin-Madison, 4245 Medical Science Center, 1300 Univ. Ave., Madison, WI 53706 (e-mail: katayama{at}htc.nagoya-u.ac.jp)

The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.


   REFERENCES
TOP
 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
 GRANTS
 REFERENCES
 

  1. Amann M, Eldridge MW, Lovering AT, Stickland MK, Pegelow DF, Dempsey JA. Arterial oxygenation influences central motor output and exercise performance via effects on peripheral locomotor muscle fatigue in humans. J Physiol 575: 937–952, 2006.[Abstract/Free Full Text]
  2. Amann M, Romer LM, Pegelow DF, Jacques AJ, Hess CJ, Dempsey JA. Effects of arterial oxygen content on peripheral locomotor muscle fatigue. J Appl Physiol 101: 119–127, 2006.[Abstract/Free Full Text]
  3. Arbogast S, Vassilakopoulos T, Darques JL, Duvauchelle JB, Jammes Y. Influence of oxygen supply on activation of group IV muscle afferents after low-frequency muscle stimulation. Muscle Nerve 23: 1187–1193, 2000.[CrossRef][ISI][Medline]
  4. Barnes W. The relationship between maximum isometric strength and intramuscular circulatory occlusion. Ergonomics 23: 351–357, 1980.[Medline]
  5. Bendahan D, Badier M, Jammes Y, Confort-Gouny S, Salvan AM, Guillot C, Cozzone PJ. Metabolic and myoelectrical effects of acute hypoxaemia during isometric contraction of forearm muscles in humans: a combined 31P-magnetic resonance spectroscopy-surface electromyogram (MRS-SEMG) study. Clin Sci (Lond) 94: 279–286, 1998.[Medline]
  6. Bowie W, Cumming GR. Sustained handgrip-reproducibility; effects of hypoxia. Med Sci Sports 3: 24–31, 1971.[Medline]
  7. Bruton JD, Lannergren J, Westerblad H. Effects of CO2-induced acidification on the fatigue resistance of single mouse muscle fibers at 28°C. J Appl Physiol 85: 478–483, 1998.[Abstract/Free Full Text]
  8. Chasiotis D, Hultman E, Sahlin K. Acidotic depression of cyclic AMP accumulation and phosphorylase b to a transformation in skeletal muscle of man. J Physiol 335: 197–204, 1982.
  9. Dahlstedt AJ, Katz A, Westerblad H. Role of myoplasmic phosphate in contractile function of skeletal muscle: studies on creatine kinase-deficient mice. J Physiol 533: 379–388, 2001.
  10. Debold EP, Fitts RH. The effects of temperature and Pi on single muscle fiber contractile properties. Biophys J 78: 119A, 2000.
  11. Degens H, Horneros JMS, Hopman MTE. Acute hypoxia limits endurance but does not affect muscle contractile properties. Muscle Nerve 33: 532–537, 2006.[CrossRef][ISI][Medline]
  12. Dimitrova NA, Dimitrov GV. Interpretation of EMG changes with fatigue: facts, pitfalls, and fallacies. J Electromyogr Kinesiol 13: 13–36, 2003.[CrossRef][ISI][Medline]
  13. Donaldson SKB, Hermansen L, Bolles L. Differential, direct effects of H+ on Ca2+ -activated force of skinned fibers from the soleus, cardiac and adductor magnus muscles of rabbits. Pflügers Arch 376: 55–65, 1978.[CrossRef][ISI][Medline]
  14. Dousset E, Steinberg JG, Balon N, Jammes Y. Effects of acute hypoxemia on force and surface EMG during sustained handgrip. Muscle Nerve 24: 364–371, 2001.[CrossRef][ISI][Medline]
  15. Dutka TL, Cole L, Lamb GD. Calcium phosphate precipitation in the sarcoplasmic reticulum reduces action potential-mediated Ca2+ release in mammalian skeletal muscle. Am J Physiol Cell Physiol 289: C1502–C1512, 2005.[Abstract/Free Full Text]
  16. Edwards R. Human muscle function and fatigue. In: Human Muscle Fatigue Physiological Mechanisms, edited by Porter R and Whelan J. London: Pitman, 1981, p. 1–8.
  17. Eiken O, Tesch PA. Effects of hyperoxia and hypoxia on dynamic and sustained static performance of the human quadriceps muscle. Acta Physiol Scand 122: 629–633, 1984.[ISI][Medline]
  18. Enoka RM, Stuart DG. Neurobiology of muscle fatigue. J Appl Physiol 72: 1631–1648, 1992.[Abstract/Free Full Text]
  19. Fabiato A, Fabiato F. Effects of pH on the myofilaments and the sarcoplasmic reticulum of skinned cells from cardiac and skeletal muscles. J Physiol 276: 233–255, 1978.[Abstract/Free Full Text]
  20. Fryer MW, Owen VJ, Lamb GD, Stephenson DG. Effects of creatine phosphate and Pi on Ca2+ movements and tension development in rat skinned skeletal muscle fibers. J Physiol 482: 123–140, 1995.[ISI][Medline]
  21. Fulco CS, Cymerman A, Muza SR, Rock PB, Pandolf KB, Lewis SF. Adductor pollicis muscle fatigue during acute and chronic altitude exposure and return to sea level. J Appl Physiol 77: 179–183, 1994.[Abstract/Free Full Text]
  22. Fulco CS, Lewis SF, Frykman PN, Boushel R, Smith S, Harman EA, Cymerman A, Pandolf KB. Muscle fatigue and exhaustion during dynamic leg exercise in normoxia and hypobaric hypoxia. J Appl Physiol 81: 1891–1900, 1996.[Abstract/Free Full Text]
  23. Gandevia SC. Spinal and supraspinal factors in human muscle fatigue. Physiol Rev 81: 1725–1789, 2001.[Abstract/Free Full Text]
  24. Goldberg LJ, Derfler B. Relationship among recruitment order, spike amplitude, and twitch tension of single motor units in human masseter muscle. J Neurophysiol 40: 879–890, 1977.[Free Full Text]
  25. Haseler LJ, Hogan MC, Richardson RS. Skeletal muscle phosphocreatine recovery in exercise-trained humans is dependent on O2 availability. J Appl Physiol 86: 2013–2018, 1999.[Abstract/Free Full Text]
  26. Haseler LJ, Richardson RS, Videen JS, Hogan MC. Phosphocreatine hydrolysis during submaximal exercise: the effect of FIO2. J Appl Physiol 85: 1457–1463, 1998.[Abstract/Free Full Text]
  27. Hogan MC, Richardson RS, Haseler LJ. Human muscle performance and PCr hydrolysis with varied inspired oxygen fractions: a 31P-MRS study. J Appl Physiol 86: 1367–1373, 1999.[Abstract/Free Full Text]
  28. Keenan KG, Farina D, Maluf KS, Merletti R, Enoka RM. Influence of amplitude cancellation on the simulated surface electromyogram. J Appl Physiol 98: 120–131, 2005.[Abstract/Free Full Text]
  29. Kufel TJ, Pineda LA, Mador MJ. Comparison of potentiated and unpotentiated twitches as an index of muscle fatigue. Muscle Nerve 25: 438–444, 2002.[CrossRef][ISI][Medline]
  30. Lamb GD, Stephenson DG, Bangsbo J, Juel C. Point:Counterpoint: lactic acid accumulation is an advantage/disadvantage during muscle activity. J Appl Physiol 100: 1410–1414, 2006.[Free Full Text]
  31. Ma J, Fill M, Knudson CM, Campbell KP, Coronado R. Ryanodine receptor of skeletal muscle is a gap junction-type channel. Science 242: 99–102, 1988.[Abstract/Free Full Text]
  32. Mador MJ, Bozkanat E, Kufel TJ. Quadriceps fatigue after cycle exercise in patients with COPD compared with healthy control subjects. Chest 123: 1104–1111, 2003.
  33. Mador MJ, Deniz O, Aggarwal A, Kufel TJ. Quadriceps fatigability after single muscle exercise in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 168: 102–108, 2003.[Abstract/Free Full Text]
  34. Mador MJ, Kufel TJ, Pineda LA, Steinwald A, Aggarwal A, Upadhyay AM, Khan MA. Effect of pulmonary rehabilitation on quadriceps fatigability during exercise. Am J Respir Crit Care Med 163: 930–935, 2001.[Abstract/Free Full Text]
  35. Mador JM, Magalang UJ, Kufel TJ. Twitch potentiation following voluntary diaphragmatic contraction. Am J Respir Crit Care Med 149: 739–743, 1994.[Abstract]
  36. Merton PA. Voluntary strength and fatigue. J Physiol 123: 553–564, 1954.[Free Full Text]
  37. Metzger JM, Fitts RH. Fatigue from high- and low-frequency muscle stimulation: contractile and biochemical alterations. J Appl Physiol 62: 2075–2082, 1987.[Abstract/Free Full Text]
  38. Moritani T, Muro M, Nagata A. Intramuscular and surface electromyogram changes during muscle fatigue. J Appl Physiol 60: 1179–1185, 1986.[Abstract/Free Full Text]
  39. Orizio C, Esposito F, Veicsteinas A. Effect of acclimatization to high altitude (5,050 m) on motor unit activation pattern and muscle performance. J Appl Physiol 77: 2840–2844, 1994.[Abstract/Free Full Text]
  40. Pate E, Bhimani M, Franks-Skiba K, Cooke R. Reduced effect of pH on skinned rabbit psoas muscle mechanics at high temperatures: implications for fatigue. J Physiol 486: 689–694, 1995.[ISI][Medline]
  41. Pedersen TH, Nielsen OB, Lamb GD, Stephenson DG. Intracellular acidosis enhances the excitability of working muscle. Science 305: 1144–1147, 2004.[Abstract/Free Full Text]
  42. Polkey MI, Kyroussis D, Hamnegard CH, Mills GH, Green M, Moxham J. Quadriceps strength and fatigue assessed by magnetic stimulation of the femoral nerve in man. Muscle Nerve 19: 549–555, 1996.[CrossRef][ISI][Medline]
  43. Romer LM, Haverkamp HC, Lovering AT, Pegelow DF, Dempsey JA. Effect of exercise-induced arterial hypoxemia on quadriceps muscle fatigue in healthy humans. Am J Physiol Regul Integr Comp Physiol 290: R365–R375, 2006.[Abstract/Free Full Text]
  44. Romer LM, Lovering AT, Haverkamp HC, Pegelow DF, Dempsey JA. Effect of inspiratory muscle work on peripheral fatigue of locomotor muscles in healthy humans. J Physiol 571: 425–439, 2006.[Abstract/Free Full Text]
  45. Sandiford SD, Green HJ, Duhamel TA, Schertzer JD, Perco JD, Ouyang J. Muscle Na-K-pump and fatigue responses to progressive exercise in normoxia and hypoxia. Am J Physiol Regul Integr Comp Physiol 289: R441–R449, 2005.[Abstract/Free Full Text]
  46. Taylor AD, Bronks R, Smith P, Humphries B. Myoelectric evidence of peripheral muscle fatigue during exercise in severe hypoxia: some references to m. vastus lateralis myosin heavy chain composition. Eur J Appl Physiol 75: 151–159, 1997.
  47. Westerblad H, Allen DG, Lannergren J. Muscle fatigue: lactic acid or inorganic phosphate the major cause? News Physiol Sci 17: 17–21, 2002.[Abstract/Free Full Text]
  48. Young A, Wright J, Knapik J, Cymerman A. Skeletal muscle strength during exposure to hypobaric hypoxia. Med Sci Sports Exerc 12: 330–335, 1980.




This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
292/3/R1279    most recent
00554.2006v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via ISI Web of Science (5)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Katayama, K.
Right arrow Articles by Dempsey, J. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Katayama, K.
Right arrow Articles by Dempsey, J. A.

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Visit Other APS Journals Online
Copyright © 2007 by the American Physiological Society.