Exercise-induced abdominal muscle fatigue in healthy humans.

The abdominal muscles have been shown to fatigue in response to voluntary isocapnic hyperpnea using direct nerve stimulation techniques. We investigated whether the abdominal muscles fatigue in response to dynamic lower limb exercise using such techniques. Eleven male subjects [peak oxygen uptake (VO2 peak) = 50.0 +/- 1.9 (SE) ml.kg(-1).min(-1)] cycled at >90% VO2 peak to exhaustion (14.2 +/- 4.2 min). Abdominal muscle function was assessed before and up to 30 min after exercise by measuring the changes in gastric pressure (Pga) after the nerve roots supplying the abdominal muscles were magnetically stimulated at 1-25 Hz. Immediately after exercise there was a decrease in Pga at all stimulation frequencies (mean -25 +/- 4%; P < 0.001) that persisted up to 30 min postexercise (-12 +/- 4%; P = 0.001). These reductions were unlikely due to changes in membrane excitability because amplitude, duration, and area of the rectus abdominis M wave were unaffected. Declines in the Pga response to maximal voluntary expiratory efforts occurred after exercise (158 +/- 13 before vs. 145 +/- 10 cmH2O after exercise; P = 0.005). Voluntary activation, assessed using twitch interpolation, did not change (67 +/- 6 before vs. 64 +/- 2% after exercise; P = 0.20), and electromyographic activity of the rectus abdominis and external oblique increased during these volitional maneuvers. These data provide new evidence that the abdominal muscles fatigue after sustained, high-intensity exercise and that the fatigue is primarily due to peripheral mechanisms.     

Inspiratory muscle work in acute hypoxia influences locomotor muscle fatigue and exercise performance of healthy humans

Our aim was to isolate the independent effects of 1) inspiratory muscle work (W(b)) and 2) arterial hypoxemia during heavy-intensity exercise in acute hypoxia on locomotor muscle fatigue. Eight cyclists exercised to exhaustion in hypoxia [inspired O(2) fraction (Fi(O(2))) = 0.15, arterial hemoglobin saturation (Sa(O(2))) = 81 +/- 1%; 8.6 +/- 0.5 min, 273 +/- 6 W; Hypoxia-control (Ctrl)] and at the same work rate and duration in normoxia (Sa(O(2)) = 95 +/- 1%; Normoxia-Ctrl). These trials were repeated, but with a 35-80% reduction in W(b) achieved via proportional assist ventilation (PAV). Quadriceps twitch force was assessed via magnetic femoral nerve stimulation before and 2 min after exercise. The isolated effects of W(b) in hypoxia on quadriceps fatigue, independent of reductions in Sa(O(2)), were revealed by comparing Hypoxia-Ctrl and Hypoxia-PAV at equal levels of Sa(O(2)) (P = 0.10). Immediately after hypoxic exercise potentiated twitch force of the quadriceps (Q(tw,pot)) decreased by 30 +/- 3% below preexercise baseline, and this reduction was attenuated by about one-third after PAV exercise (21 +/- 4%; P = 0.0007). This effect of W(b) on quadriceps fatigue occurred at exercise work rates during which, in normoxia, reducing W(b) had no significant effect on fatigue. The isolated effects of reduced Sa(O(2)) on quadriceps fatigue, independent of changes in W(b), were revealed by comparing Hypoxia-PAV and Normoxia-PAV at equal levels of W(b). Q(tw,pot) decreased by 15 +/- 2% below preexercise baseline after Normoxia-PAV, and this reduction was exacerbated by about one-third after Hypoxia-PAV (-22 +/- 3%; P = 0.034). We conclude that both arterial hypoxemia and W(b) contribute significantly to the rate of development of locomotor muscle fatigue during exercise in acute hypoxia; this occurs at work rates during which, in normoxia, W(b) has no effect on peripheral fatigue.     

Abdominal muscle fatigue following exercise in chronic obstructive pulmonary disease

Background

In patients with chronic obstructive pulmonary disease, a restriction on maximum ventilatory capacity contributes to exercise limitation. It has been demonstrated that the diaphragm in COPD is relatively protected from fatigue during exercise. Because of expiratory flow limitation the abdominal muscles are activated early during exercise in COPD. This adds significantly to the work of breathing and may therefore contribute to exercise limitation. In healthy subjects, prior expiratory muscle fatigue has been shown itself to contribute to the development of quadriceps fatigue. It is not known whether fatigue of the abdominal muscles occurs during exercise in COPD.

Methods

Twitch gastric pressure (TwT10Pga), elicited by magnetic stimulation over the 10^th thoracic vertebra and twitch transdiaphragmatic pressure (TwPdi), elicited by bilateral anterolateral magnetic phrenic nerve stimulation were measured before and after symptom-limited, incremental cycle ergometry in patients with COPD.

Results

Twenty-three COPD patients, with a mean (SD) FEV₁ 40.8(23.1)% predicted, achieved a mean peak workload of 53.5(15.9) W. Following exercise, TwT₁₀Pga fell from 51.3(27.1) cmH₂O to 47.4(25.2) cmH₂O (p = 0.011). TwPdi did not change significantly; pre 17.0(6.4) cmH₂O post 17.5(5.9) cmH₂O (p = 0.7). Fatiguers, defined as having a fall TwT10Pga ≥ 10% had significantly worse lung gas transfer, but did not differ in other exercise parameters.

Conclusions

In patients with COPD, abdominal muscle but not diaphragm fatigue develops following symptom limited incremental cycle ergometry. Further work is needed to establish whether abdominal muscle fatigue is relevant to exercise limitation in COPD, perhaps indirectly through an effect on quadriceps fatigability.     

Effect of acute severe hypoxia on peripheral fatigue and endurance capacity in healthy humans

We hypothesized that severe hypoxia limits exercise performance via decreased contractility of limb locomotor muscles. Nine male subjects [mean +/- SE maximum O(2) uptake (Vo(2 max)) = 56.5 +/- 2.7 ml x kg(-1) x min(-1)] cycled at > or =90% Vo(2 max) to exhaustion in normoxia [NORM-EXH; inspired O(2) fraction (Fi(O(2))) = 0.21, arterial O(2) saturation (Sp(O(2))) = 93 +/- 1%] and hypoxia (HYPOX-EXH; Fi(O(2)) = 0.13, Sp(O(2)) = 76 +/- 1%). The subjects also exercised in normoxia for a time equal to that achieved in hypoxia (NORM-CTRL; Sp(O(2)) = 96 +/- 1%). Quadriceps twitch force, in response to supramaximal single (nonpotentiated and potentiated 1 Hz) and paired magnetic stimuli of the femoral nerve (10-100 Hz), was assessed pre- and at 2.5, 35, and 70 min postexercise. Hypoxia exacerbated exercise-induced peripheral fatigue, as evidenced by a greater decrease in potentiated twitch force in HYPOX-EXH vs. NORM-CTRL (-39 +/- 4 vs. -24 +/- 3%, P < 0.01). Time to exhaustion was reduced by more than two-thirds in HYPOX-EXH vs. NORM-EXH (4.2 +/- 0.5 vs. 13.4 +/- 0.8 min, P < 0.01); however, peripheral fatigue was not different in HYPOX-EXH vs. NORM-EXH (-34 +/- 4 vs. -39 +/- 4%, P > 0.05). Blood lactate concentration and perceptions of limb discomfort were higher throughout HYPOX-EXH vs. NORM-CTRL but were not different at end-exercise in HYPOX-EXH vs. NORM-EXH. We conclude that severe hypoxia exacerbates peripheral fatigue of limb locomotor muscles and that this effect may contribute, in part, to the early termination of exercise.     

Increasing blood flow before exercise in spinal cord-injured individuals does not alter muscle fatigue.

Previous studies have shown increased fatigue in paralyzed muscle of spinal cord-injured (SCI) patients (Castro M, Apple D Jr, Hillegass E, and Dudley GA. Eur J Appl Physiol 80: 373-378, 1999; Gerrits H, Hopman MTE, Sargeant A, and de Haan A. Clin Physiol 21: 105-113, 2001). Our purpose was to determine whether the increased muscle fatigue could be due to a delayed rise in blood flow at the onset of exercise in SCI individuals. Isometric electrical stimulation was used to induce fatigue in the quadriceps femoris muscle of seven male, chronic (>1 yr postinjury), complete (American Spinal Injury Association, category A) SCI subjects. Cuff occlusion was used to elevate blood flow before electrical stimulation, and the magnitude of fatigue was compared with a control condition of electrical stimulation without prior cuff occlusion. Blood flow was measured in the femoral artery by Doppler ultrasound. Prior cuff occlusion increased blood flow in the first 30 s of stimulation compared with the No-Cuff condition (1,350 vs. 680 ml/min, respectively; P < 0.001), although blood flow at the end of stimulation was the same between conditions (1,260 +/- 140 vs. 1,160 +/- 370 ml/min, Cuff and No-Cuff condition, respectively; P = 0.511). Muscle fatigue was not significantly different between prior cuff occlusion and the control condition (32 +/- 13 vs. 35 +/- 10%; P = 0.670). In conclusion, increased muscle fatigue in SCI individuals is not associated with the prolonged time for blood flow to increase at the onset of exercise.     

Ventilatory muscle recruitment in exercise with O2 in obstructed patients with mild hypoxemia

Respiratory muscle dysfunction limits exercise endurance in severe chronic airflow obstruction (CAO). To investigate whether inspiring O2 alters ventilatory muscle recruitment and improves exercise endurance, we recorded pleural (Ppl) and gastric (Pga) pressures while breathing air or 30% O2 during leg cycling in six patients with severe CAO, mild hypoxemia, and minimal arterial O2 desaturation with exercise. At rest, mean (+/- SD) transdiaphragmatic pressure (Pdi) was lower inspiring 30% O2 compared with air (23 +/- 4 vs. 26 +/- 7 cmH2O, P less than 0.05), but the pattern of Ppl and Pga contraction was identical while breathing either gas mixture. Maximal transdiaphragmatic pressure was similar breathing air or 30% O2 (84 +/- 30 vs. 77 +/- 30 cmH2O). During exercise, Pdi increased similarly while breathing air or 30% O2, but the latter was associated with a significant increase in peak inspiratory Pga and decreases in peak inspiratory Ppl and expiratory Pga. In five out of six patients, exercise endurance increased with O2 (671 +/- 365 vs. 362 +/- 227 s, P less than 0.05). We conclude that exercise with O2 alters ventilatory muscle recruitment and increases exercise endurance. During exercise inspiring O2, the diaphragm performs more ventilatory work which may prevent overloading the accessory muscles of respiration.     

Supraspinal fatigue does not explain the sex difference in muscle fatigue of maximal contractions.

Young women are less fatigable than young men for maximal and submaximal contractions, but the contribution of supraspinal fatigue to the sex difference is not known. This study used cortical stimulation to compare the magnitude of supraspinal fatigue during sustained isometric maximal voluntary contractions (MVCs) performed with the elbow flexor muscles of young men and women. Eight women (25.6 +/- 3.6 yr, mean +/- SD) and 9 men (25.4 +/- 3.8 yr) performed six sustained MVCs (22-s duration each, separated by 10 s). Before the fatiguing contractions, the men were stronger than the women (75.9 +/- 9.2 vs. 42.7 +/- 8.0 N.m; P < 0.05) in control MVCs. Voluntary activation measured with cortical stimulation before fatigue was similar for the men and women during the final control MVC (95.7 +/- 3.0 vs. 93.3 +/- 3.6%; P > 0.05) and at the start of the fatiguing task (P > 0.05). By the end of the six sustained fatiguing MVCs, the men exhibited greater absolute and relative reductions in torque (65 +/- 3% of initial MVC) than the women (52 +/- 9%; P < 0.05). The increments in torque (superimposed twitch) generated by motor cortex stimulation during each 22-s maximal effort increased with fatigue (P < 0.05). Superimposed twitches were similar for men and women throughout the fatiguing task (5.5 +/- 4.1 vs. 7.3 +/- 4.7%; P > 0.05), as well as in the last sustained contraction (7.8 +/- 5.9 vs. 10.5 +/- 5.5%) and in brief recovery MVCs. Voluntary activation determined using an estimated control twitch was similar for the men and women at the start of the sustained maximal contractions (91.4 +/- 7.4 vs. 90.4 +/- 6.8%, n = 13) and end of the sixth contraction (77.2 +/- 13.3% vs. 73.1 +/- 19.6%, n = 10). The increase in the area of the motor-evoked potential and duration of the silent period did not differ for men and women during the fatiguing task. However, estimated resting twitch amplitude and the peak rates of muscle relaxation showed greater relative reductions at the end of the fatiguing task for the men than the women. These results indicate that the sex difference in fatigue of the elbow flexor muscles is not explained by a difference in supraspinal fatigue in men and women but is largely due to a sex difference of mechanisms located within the elbow flexor muscles.     

Effect of respiratory muscle fatigue on subsequent exercise performance.

The purpose of this study was to determine whether induction of inspiratory muscle fatigue might impair subsequent exercise performance. Ten healthy subjects cycled 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, once immediately after induction of fatigue, whereas the other two episodes served as controls. Fatigue was achieved by having the subjects breathe against an inspiratory threshold load while generating 80% of their predetermined maximal mouth pressure until they could no longer reach the target pressure. After induction of fatigue, exercise time was reduced compared with control, 238 +/- 69 vs. 311 +/- 96 (SD) s (P less than 0.001). During the last minute of exercise, oxygen consumption and heart rate were lower after induction of fatigue than during control, 2,234 +/- 472 vs. 2,533 +/- 548 ml/min (P less than 0.002) and 167 +/- 15 vs. 177 +/- 12 beats/min (P less than 0.002). At exercise isotime, minutes ventilation and the visual analogue scale for 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 conclude that induction of inspiratory muscle fatigue can impair subsequent performance of high-intensity exercise and alter the pattern of breathing during such exercise.     

Increased fatigue resistance of respiratory muscles during exercise after respiratory muscle endurance training

Respiratory muscle fatigue develops during exhaustive exercise and can limit exercise performance. Respiratory muscle training, in turn, can increase exercise performance. We investigated whether respiratory muscle endurance training (RMT) reduces exercise-induced inspiratory and expiratory muscle fatigue. Twenty-one healthy, male volunteers performed twenty 30-min sessions of either normocapnic hyperpnoea (n = 13) or sham training (CON, n = 8) over 4-5 wk. Before and after training, subjects performed a constant-load cycling test at 85% maximal power output to exhaustion (PRE(EXH), POST(EXH)). A further posttraining test was stopped at the pretraining duration (POST(ISO)) i.e., isotime. Before and after cycling, transdiaphragmatic pressure was measured during cervical magnetic stimulation to assess diaphragm contractility, and gastric pressure was measured during thoracic magnetic stimulation to assess abdominal muscle contractility. Overall, RMT did not reduce respiratory muscle fatigue. However, in subjects who developed >10% of diaphragm or abdominal muscle fatigue in PRE(EXH), fatigue was significantly reduced after RMT in POST(ISO) (inspiratory: -17 +/- 6% vs. -9 +/- 10%, P = 0.038, n = 9; abdominal: -19 +/- 10% vs. -11 +/- 11%, P = 0.038, n = 9), while sham training had no significant effect. Similarly, cycling endurance in POST(EXH) did not improve after RMT (P = 0.071), while a significant improvement was seen in the subgroup with >10% of diaphragm fatigue after PRE(EXH) (P = 0.017), but not in the sham training group (P = 0.674). However, changes in cycling endurance did not correlate with changes in respiratory muscle fatigue. In conclusion, RMT decreased the development of respiratory muscle fatigue during intensive exercise, but this change did not seem to improve cycling endurance.     

Coexistence of potentiation and low-frequency fatigue during voluntary exercise in human skeletal muscle

The role of muscle potentiation in overcoming low-frequency fatigue (LFF) as it developed during submaximal voluntary exercise was investigated in eight males (age 26.4 +/- 0.7 years, mean +/- SE) performing isometric leg extension at approximately 30% of maximal voluntary contraction for 60 min using a 0.5-duty cycle (1 s contraction, 1 s rest). At 5, 20, 40, and 60 min, exercise was interrupted for 3 min, and the maximum positive rate of force development (+dF/dtmax) and maximal twitch force (Pt) were measured in maximal twitch contractions at 0, 1, 2, and 3 min of rest (R0, R1, R2, R3); they were also measured at 15 min of recovery following the entire 60-min exercise period. These measures were compared with pre-exercise (PRE) as an indicator of potentiation. Force at low frequency (10 Hz) was also measured at R0, R1, R2, and R3, and at 15 min of recovery, while force at high frequency (100 Hz) was measured only at R0 and R3 and in recovery. Voluntary exercise increased twitch +dF/dtmax at R0 following 5, 20, 40, and 60 min of exercise, from 2553 +/- 150 N/s at PRE to 39%, 41%, 42%, and 36% above PRE, respectively (P<0.005). Twitch +dF/dtmax decayed at brief rest (R3) following 20, 40, and 60 min of exercise (P<0.05). Pt at R0 following 5 and 20 min of exercise was above that at PRE (P<0.05), indicating that during the early phase of moderate-intensity repetitive exercise, potentiation occurs in the relative absence of LFF. At 40 and 60 min of exercise, Pt at R0 was unchanged from PRE. The LFF (10 Hz) induced by the protocol was evident at 40 and 60 min (R0-R3; P<0.05) and at 15 min following exercise (P<0.05). High-frequency force was not significantly compromised by the protocol. Since twitch force was maintained, these results suggest that as exercise progresses, LFF develops, which can be compensated for by potentiation.     

Reversal of muscle fatigue during 16 h of heavy intermittent cycle exercise.

This study examined the effects of extended sessions of heavy intermittent exercise on quadriceps muscle fatigue and weakness. Twelve untrained volunteers (10 men and 2 women), with a peak oxygen consumption of 44.3 +/- 2.3 ml.kg(-1).min(-1), exercised at approximately 91% peak oxygen consumption for 6 min once per hour for 16 h. Muscle isometric properties assessed before and after selected repetitions (R1, R2, R4, R7, R12, and R15) were used to quantitate fatigue (before vs. after repetitions) and weakness (before vs. before repetitions). Muscle fatigue at R1 was indicated by reductions (P < 0.05) in peak twitch force (135 +/- 13 vs. 106 +/- 11 N) and by a reduction (P < 0.05) in the force-frequency response, which ranged between approximately 53% at 10 Hz (113 +/- 12 vs. 52.6 +/- 7.4 N) and approximately 17% at 50 Hz (324 +/- 27 vs. 270 +/- 30 N). No recovery of force, regardless of stimulation frequency, was observed during the 54 min between R1 and R2. At R2 and for all subsequent repetitions, no reduction in force, regardless of stimulation frequency, was generally found after the exercise. The only exception was for R2, where, at 20 Hz, force was reduced (P < 0.05) by 18%. At R15, force before repetitions for high frequencies (i.e., 100 Hz) returned to R1 (333 +/- 29 vs. 324 +/- 27 N), whereas force at low frequency (i.e., 10 Hz) was only partially (P < 0.05) recovered (113 +/- 12 vs. 70 +/- 6.6 N). It is concluded that multiple sessions of heavy exercise can reverse the fatigue noted early and reduce or eliminate weakness depending on the frequency of stimulation.     

Effect of exercise-induced arterial hypoxemia on quadriceps muscle fatigue in healthy humans

The effect of exercise-induced arterial hypoxemia (EIAH) on quadriceps muscle fatigue was assessed in 11 male endurance-trained subjects [peak O2 uptake (VO2 peak) = 56.4 +/- 2.8 ml x kg(-1) x min(-1); mean +/- SE]. Subjects exercised on a cycle ergometer at >or=90% VO2 peak) to exhaustion (13.2 +/- 0.8 min), during which time arterial O2 saturation (Sa(O2)) fell from 97.7 +/- 0.1% at rest to 91.9 +/- 0.9% (range 84-94%) at end exercise, primarily because of changes in blood pH (7.183 +/- 0.017) and body temperature (38.9 +/- 0.2 degrees C). On a separate occasion, subjects repeated the exercise, for the same duration and at the same power output as before, but breathed gas mixtures [inspired O2 fraction (Fi(O2)) = 0.25-0.31] that prevented EIAH (Sa(O2) = 97-99%). Quadriceps muscle fatigue was assessed via supramaximal paired magnetic stimuli of the femoral nerve (1-100 Hz). Immediately after exercise at Fi(O2) 0.21, the mean force response across 1-100 Hz decreased 33 +/- 5% compared with only 15 +/- 5% when EIAH was prevented (P < 0.05). In a subgroup of four less fit subjects, who showed minimal EIAH at Fi(O2) 0.21 (Sa(O2) = 95.3 +/- 0.7%), the decrease in evoked force was exacerbated by 35% (P < 0.05) in response to further desaturation induced via Fi(O2) 0.17 (Sa(O2) = 87.8 +/- 0.5%) for the same duration and intensity of exercise. We conclude that the arterial O2 desaturation that occurs in fit subjects during high-intensity exercise in normoxia (-6 +/- 1% DeltaSa(O2) from rest) contributes significantly toward quadriceps muscle fatigue via a peripheral mechanism.     

Glucose formation in human skeletal muscle. Influence of glycogen content.

Eight men exercised at 66% of their maximal isometric force to fatigue after prior decrease in the glycogen store in one leg (low-glycogen, LG). The exercise was repeated with the contralateral leg (control) at the same relative intensity and for the same duration. Muscle (quadriceps femoris) glycogen content decreased in the LG leg from 199 +/- 17 (mean +/- S.E.M.) to 163 +/- 16 mmol of glucosyl units/kg dry wt. (P less than 0.05), and in the control leg from 311 +/- 23 to 270 +/- 18 mmol/kg (P less than 0.05). The decrease in glycogen corresponded to a similar accumulation of glycolytic intermediates. Muscle glucose increased in the LG leg during the contraction, from 1.8 +/- 0.1 to 4.3 +/- 0.6 mmol/kg dry wt. (P less than 0.01), whereas no significant increase occurred in the control leg (P greater than 0.05). It is concluded that during exercise glucose is formed from glycogen through the debranching enzyme when muscle glycogen is decreased to values below about 200 mmol/kg dry wt.     

Effects of respiratory muscle work on exercise performance.

The normal respiratory muscle effort at maximal exercise requires a significant fraction of cardiac output and causes leg blood flow to fall. We questioned whether the high levels of respiratory muscle work experienced in heavy exercise would affect performance. Seven male cyclists [maximal O(2) consumption (VO(2)) 63 +/- 5 ml. kg(-1). min(-1)] each completed 11 randomized trials on a cycle ergometer at a workload requiring 90% maximal VO(2). Respiratory muscle work was either decreased (unloading), increased (loading), or unchanged (control). Time to exhaustion was increased with unloading in 76% of the trials by an average of 1.3 +/- 0.4 min or 14 +/- 5% and decreased with loading in 83% of the trials by an average of 1.0 +/- 0.6 min or 15 +/- 3% compared with control (P < 0.05). Respiratory muscle unloading during exercise reduced VO(2), caused hyperventilation, and reduced the rate of change in perceptions of respiratory and limb discomfort throughout the duration of exercise. These findings demonstrate that the work of breathing normally incurred during sustained, heavy-intensity exercise (90% VO(2)) has a significant influence on exercise performance. We speculate that this effect of the normal respiratory muscle load on performance in trained male cyclists is due to the associated reduction in leg blood flow, which enhances both the onset of leg fatigue and the intensity with which both leg and respiratory muscle efforts are perceived.     

Glucose clearance in aged trained skeletal muscle during maximal insulin with superimposed exercise.

Insulin and muscle contractions are major stimuli for glucose uptake in skeletal muscle and have in young healthy people been shown to be additive. We studied the effect of superimposed exercise during a maximal insulin stimulus on glucose uptake and clearance in trained (T) (1-legged bicycle training, 30 min/day, 6 days/wk for 10 wk at approximately 70% of maximal O(2) uptake) and untrained (UT) legs of healthy men (H) [n = 6, age 60 +/- 2 (SE) yr] and patients with Type 2 diabetes mellitus (DM) (n = 4, age 56 +/- 3 yr) during a hyperinsulinemic ( approximately 16,000 pmol/l), isoglycemic clamp with a final 30 min of superimposed two-legged exercise at 70% of individual maximal heart rate. With superimposed exercise, leg glucose extraction decreased (P < 0.05), and leg blood flow and leg glucose clearance increased (P < 0.05), compared with hyperinsulinemia alone. During exercise, leg blood flow was similar in both groups of subjects and between T and UT legs, whereas glucose extraction was always higher (P < 0.05) in T compared with UT legs (15.8 +/- 1.2 vs. 14.6 +/- 1.8 and 11.9 +/- 0.8 vs. 8.8 +/- 1.8% for H and DM, respectively) and leg glucose clearance was higher in T (H: 73 +/- 8, DM: 70 +/- 10 ml. min(-1). kg leg(-1)) compared with UT (H: 63 +/- 8, DM: 45 +/- 7 ml. min(-1). kg leg(-1)) but not different between groups (P > 0.05). From these results it can be concluded that, in both diabetic and healthy aged muscle, exercise adds to a maximally insulin-stimulated glucose clearance and that glucose extraction and clearance are both enhanced by training.     

Inactivation of human muscle Na+-K+-ATPase in vitro during prolonged exercise is increased with hypoxia.

This study investigated the effects of prolonged exercise performed in normoxia (N) and hypoxia (H) on neuromuscular fatigue, membrane excitability, and Na+-K+ -ATPase activity in working muscle. Ten untrained volunteers [peak oxygen consumption (Vo2peak) = 42.1 +/- 2.8 (SE) ml x kg(-1) x min(-1)] performed 90 min of cycling during N (inspired oxygen fraction = 0.21) and during H (inspired oxygen fraction = 0.14) at approximately 50% of normoxic Vo2peak. During N, 3-O-methylfluorescein phosphatase activity (nmol x mg protein(-1) x h(-1)) in vastus lateralis, used as a measure of Na+-K+-ATPase activity, decreased (P < 0.05) by 21% at 30 min of exercise compared with rest (101 +/- 53 vs. 79.6 +/- 4.3) with no further reductions observed at 90 min (72.8 +/- 8.0). During H, similar reductions (P < 0.05) were observed during the first 30 min (90.8 +/- 5.3 vs. 79.0 +/- 6.3) followed by further reductions (P < 0.05) at 90 min (50.5 +/- 3.9). Exercise in N resulted in reductions (P < 0.05) in both quadriceps maximal voluntary contractile force (MVC; 633 +/- 50 vs. 477 +/- 67 N) and force at low frequencies of stimulation, namely 10 Hz (142 +/- 16 vs. 86.7 +/- 10 N) and 20 Hz (283 +/- 32 vs. 236 +/- 31 N). No changes were observed in the amplitude, duration, and area of the muscle compound action potential (M wave). Exercise in H was without additional effect in altering MVC, low-frequency force, and M-wave properties. It is concluded that, although exercise in H resulted in a greater inactivation of Na+-K+-ATPase activity compared with N, neuromuscular fatigue and membrane excitability are not differentially altered.     

Effect of acute hypoxia on respiratory muscle fatigue in healthy humans

Background

Greater diaphragm fatigue has been reported after hypoxic versus normoxic exercise, but whether this is due to increased ventilation and therefore work of breathing or reduced blood oxygenation per se remains unclear. Hence, we assessed the effect of different blood oxygenation level on isolated hyperpnoea-induced inspiratory and expiratory muscle fatigue.

Methods

Twelve healthy males performed three 15-min isocapnic hyperpnoea tests (85% of maximum voluntary ventilation with controlled breathing pattern) in normoxic, hypoxic (SpO₂ = 80%) and hyperoxic (FiO₂ = 0.60) conditions, in a random order. Before, immediately after and 30 min after hyperpnoea, transdiaphragmatic pressure (P_di,tw ) was measured during cervical magnetic stimulation to assess diaphragm contractility, and gastric pressure (P_ga,tw ) was measured during thoracic magnetic stimulation to assess abdominal muscle contractility. Two-way analysis of variance (time x condition) was used to compare hyperpnoea-induced respiratory muscle fatigue between conditions.

Results

Hypoxia enhanced hyperpnoea-induced P_di,tw and P_ga,tw reductions both immediately after hyperpnoea (P_di,tw : normoxia -22 ± 7% vs hypoxia -34 ± 8% vs hyperoxia -21 ± 8%; P_ga,tw : normoxia -17 ± 7% vs hypoxia -26 ± 10% vs hyperoxia -16 ± 11%; all P < 0.05) and after 30 min of recovery (P_di,tw : normoxia -10 ± 7% vs hypoxia -16 ± 8% vs hyperoxia -8 ± 7%; P_ga,tw : normoxia -13 ± 6% vs hypoxia -21 ± 9% vs hyperoxia -12 ± 12%; all P < 0.05). No significant difference in P_di,tw or P_ga,tw reductions was observed between normoxic and hyperoxic conditions. Also, heart rate and blood lactate concentration during hyperpnoea were higher in hypoxia compared to normoxia and hyperoxia.

Conclusions

These results demonstrate that hypoxia exacerbates both diaphragm and abdominal muscle fatigability. These results emphasize the potential role of respiratory muscle fatigue in exercise performance limitation under conditions coupling increased work of breathing and reduced O₂ transport as during exercise in altitude or in hypoxemic patients.     

Effects of arterial oxygen content on peripheral locomotor muscle fatigue.

The effect of arterial O2 content (Ca(O2)) on quadriceps fatigue was assessed in healthy, trained male athletes. On separate days, eight participants completed three constant-workload trials on a bicycle ergometer at fixed workloads (314 +/- 13 W). The first trial was performed while the subjects breathed a hypoxic gas mixture [inspired O2 fraction (Fi(O2)) = 0.15, Hb saturation = 81.6%, Ca(O2) = 18.2 ml O2/dl blood; Hypo] until exhaustion (4.5 +/- 0.4 min). The remaining two trials were randomized and time matched with Hypo. The second and third trials were performed while the subjects breathed a normoxic (Fi(O2) = 0.21, Hb saturation = 95.0%, Ca(O2) = 21.3 ml O2/dl blood; Norm) and a hyperoxic (Fi(O2) = 1.0, Hb saturation = 100%, Ca(O2) = 23.8 ml O2/dl blood; Hyper) gas mixture, respectively. Quadriceps muscle fatigue was assessed via magnetic femoral nerve stimulation (1-100 Hz) before and 2.5 min after exercise. Myoelectrical activity of the vastus lateralis was obtained from surface electrodes throughout exercise. Immediately after exercise, the mean force response across 1-100 Hz decreased from preexercise values (P < 0.01) by -26 +/- 2, -17 +/- 2, and -13 +/- 2% for Hypo, Norm, and Hyper, respectively; each of the decrements differed significantly (P < 0.05). Integrated electromyogram increased significantly throughout exercise (P < 0.01) by 23 +/- 3, 10 +/- 1, and 6 +/- 1% for Hypo, Norm, and Hyper, respectively; each of the increments differed significantly (P < 0.05). Mean power frequency fell more (P < 0.05) during Hypo (-15 +/- 2%); the difference between Norm (-7 +/- 1%) and Hyper (-6 +/- 1%) was not significant (P = 0.32). We conclude that deltaCa(O2) during strenuous systemic exercise at equal workloads and durations affects the rate of locomotor muscle fatigue development.     

Adenine nucleotide degradation in human skeletal muscle during prolonged exercise

Eight healthy men cycled at a work load corresponding to approximately 70% of maximal O2 uptake (VO2max) to fatigue (exercise I). Exercise to fatigue at the same work load was repeated after 75 min of rest (exercise II). Exercise duration averaged 65 and 21 min for exercise I and II, respectively. Muscle (quadriceps femoris) content of glycogen decreased from 492 +/- 27 to 92 +/- 20 (SE) mmol/kg dry wt and from 148 +/- 17 to 56 +/- 17 (SE) mmol/kg dry wt during exercise I and II, respectively. Muscle and blood lactate were only moderately increased during exercise. The total adenine nucleotide pool (TAN = ATP + ADP + AMP) decreased and inosine 5'-monophosphate (IMP) increased in the working muscle during both exercise I (P less than 0.001) and II (P less than 0.01). Muscle content of ammonia (NH3) increased four- and eight-fold during exercise I and II, respectively. The working legs released NH3, and plasma NH3 increased progressively during exercise. The release of NH3 at the end of exercise II was fivefold higher than that at the same time point in exercise I (P less than 0.001, exercise I vs. II). It is concluded that submaximal exercise to fatigue results in a breakdown of the TAN in the working muscle through deamination of AMP to IMP and NH3. The relatively low lactate levels demonstrate that acidosis is not a necessary prerequisite for activation of AMP deaminase. It is suggested that the higher average rate of AMP deamination during exercise II vs. exercise I is due to a relative impairment of ATP resynthesis caused by the low muscle glycogen level.     

Glucose supplements increase human muscle in vitro Na+-K+-ATPase activity during prolonged exercise

Regulation of maximal Na(+)-K(+)-ATPase activity in vastus lateralis muscle was investigated in response to prolonged exercise with (G) and without (NG) oral glucose supplements. Fifteen untrained volunteers (14 males and 1 female) with a peak aerobic power (Vo(2)(peak)) of 44.8 +/- 1.9 ml.kg(-1).min(-1); mean +/- SE cycled at approximately 57% Vo(2)(peak) to fatigue during both NG (artificial sweeteners) and G (6.13 +/- 0.09% glucose) in randomized order. Consumption of beverage began at 30 min and continued every 15 min until fatigue. Time to fatigue was increased (P < 0.05) in G compared with NG (137 +/- 7 vs. 115 +/- 6 min). Maximal Na(+)-K(+)-ATPase activity (V(max)) as measured by the 3-O-methylfluorescein phosphatase assay (nmol.mg(-1).h(-1)) was not different between conditions prior to exercise (85.2 +/- 3.3 or 86.0 +/- 3.9), at 30 min (91.4 +/- 4.7 vs. 91.9 +/- 4.1) and at fatigue (92.8 +/- 4.3 vs. 100 +/- 5.0) but was higher (P < 0.05) in G at 90 min (86.7 +/- 4.2 vs. 109 +/- 4.1). Na(+)-K(+)-ATPase content (beta(max)) measured by the vanadate facilitated [(3)H]ouabain-binding technique (pmol/g wet wt) although elevated (P < 0.05) by exercise (0<30, 90, and fatigue) was not different between NG and G. At 60 and 90 min of exercise, blood glucose was higher (P < 0.05) in G compared with NG. The G condition also resulted in higher (P < 0.05) serum insulin at similar time points to glucose and lower (P < 0.05) plasma epinephrine and norepinephrine at 90 min of exercise and at fatigue. These results suggest that G results in an increase in V(max) by mechanisms that are unclear.