Effect of ambient temperature on human skeletal muscle metabolism during fatiguing submaximal exercise.

To examine the effect of ambient temperature on metabolism during fatiguing submaximal exercise, eight men cycled to exhaustion at a workload requiring 70% peak pulmonary oxygen uptake on three separate occasions, at least 1 wk apart. These trials were conducted in ambient temperatures of 3 degrees C (CT), 20 degrees C (NT), and 40 degrees C (HT). Although no differences in muscle or rectal temperature were observed before exercise, both muscle and rectal temperature were higher (P < 0.05) at fatigue in HT compared with CT and NT. Exercise time was longer in CT compared with NT, which, in turn, was longer compared with HT (85 +/- 8 vs. 60 +/- 11 vs. 30 +/- 3 min, respectively; P < 0.05). Plasma epinephrine concentration was not different at rest or at the point of fatigue when the three trials were compared, but concentrations of this hormone were higher (P < 0.05) when HT was compared with NT, which in turn was higher (P < 0.05) compared with CT after 20 min of exercise. Muscle glycogen concentration was not different at rest when the three trials were compared but was higher at fatigue in HT compared with NT and CT, which were not different (299 +/- 33 vs. 153 +/- 27 and 116 +/- 28 mmol/kg dry wt, respectively; P < 0.01). Intramuscular lactate concentration was not different at rest when the three trials were compared but was higher (P < 0.05) at fatigue in HT compared with CT. No differences in the concentration of the total intramuscular adenine nucleotide pool (ATP + ADP + AMP), phosphocreatine, or creatine were observed before or after exercise when the trials were compared. Although intramuscular IMP concentrations were not statistically different before or after exercise when the three trials were compared, there was an exercise-induced increase (P < 0.01) in IMP. These results demonstrate that fatigue during prolonged exercise in hot conditions is not related to carbohydrate availability. Furthermore, the increased endurance in CT compared with NT is probably due to a reduced glycogenolytic rate.     

Skeletal muscle metabolism during short-term, high-intensity exercise in prepubertal and pubertal girls.

To test the hypothesis that glycolytic metabolism in muscle is attenuated in prepubertal children, (31)P-magnetic resonance spectroscopy was used to determine calf muscle intracellular pH (pH(i)) in nine prepubertal (Pre) and nine pubertal female swimmers (Pub). Maximal plantar flexion work capacity (100% MWC) was established by using a graded exercise test. Between 5 and 10 days later, calf muscle images (magnetic resonance imaging) and phosphorus spectra were acquired at rest, during 2 min of light exercise (40% MWC), and during 2 min of supramaximal exercise (140% MWC) in a 3.0-T NMR system. End-exercise pH(i) was 6.66 +/- 0.11 and 6.76 +/- 0.17 for Pub and Pre, respectively. No significant differences in the mean values for pH(i) or the P(i)-to-phosphocreatine ratio were observed between groups during the protocol; however, an interaction effect was found for the P(i)-to-phosphocreatine ratio during the supramaximal exercise challenge. Cross-sectional area of gastrocnemius was 15.12 +/- 0.46 and 9.37 +/- 0.37 cm(2) for Pub and Pre, respectively (P < 0.05). Differences in muscle size must be considered when interpreting the unlocalized magnetic resonance spectroscopy data. These results suggest that glycolytic metabolism in physically active children is not maturity dependent.     

Skeletal muscle metabolism during exercise is influenced by heat acclimation

The influence of heat acclimation on skeletal muscle metabolism during submaximal exercise was studied in 13 healthy men. The subjects performed 30 min of cycle exercise (70% of individual maximal O2 uptake) in a cool [21 degrees C, 30% relative humidity (rh)] and a hot (49 degrees C, 20% rh) environment before and again after they were heat acclimated. Aerobic metabolic rate was lower (0.1 l X min-1; P less than 0.01) during exercise in the heat compared with the cool both before and after heat acclimation. Muscle and plasma lactate accumulation with exercise was greater (P less than 0.01) in the hot relative to the cool environment both before and after acclimation. Acclimation lowered (P less than 0.01) aerobic metabolic rate as well as muscle and plasma lactate accumulation in both environments. The amount of muscle glycogen utilized during exercise in the hot environment did not differ from that in the cool either before or after acclimation. These findings indicate that accumulation of muscle lactate is increased and aerobic metabolic rate is decreased during exercise in the heat before and after heat acclimation; increased muscle glycogen utilization does not account for the increased muscle lactate accumulation during exercise under extreme heat stress; and heat acclimation lowers the aerobic metabolic rate and muscle and blood lactate accumulation during exercise in a cool as well as a hot environment.     

Skeletal muscle O2 consumption and energy metabolism during hypoxemia

We determined the relationship of O2 transport (TO2) to O2 consumption (VO2) and to changes in cellular bioenergetics in an isolated blood-perfused rabbit hindlimb preparation (n = 8) during hypoxemia. The preparations were subjected to reductions in TO2 by progressively decreasing partial pressure of arterial O2 (PaO2). At each level of PaO2 we obtained simultaneous measures of arterial and venous blood gases, venous lactate concentration, and changes in the relative concentrations of inorganic phosphate, phosphocreatine, and ATP measured with 31P magnetic resonance spectroscopy. The ratio of the change in vascular resistance (R) to the corresponding decrease in TO2 was taken as an index of vascular autoregulation with hypoxemia. Linear and logarithmic functions were fitted by least squares to the TO2-VO2 data from each experiment. TO2-VO2 relationships were characterized as O2 conforming (linear function, n = 4) or O2 regulating (logarithmic function, n = 4), depending on the goodness of fit. Those preparations showing an O2-conforming pattern had higher control VO2 (2.42 +/- 0.14 vs. 1.66 +/- 0.19 ml.min-1.kg-1; P less than 0.05) and a lesser degree of vascular autoregulation (0.07 +/- 0.03 vs. 0.21 +/- 0.02; P less than 0.01) than the O2-regulating group. Decreases in VO2 were always accompanied by increases in inorganic phosphate and lactate and decreases in phosphocreatine, indicating O2 supply limitation and anaerobic ATP production. There was no evidence of cellular adaptation to hypoxia by decreasing energy needs or of VO2 limitation by the depletion of adenine nucleotides.     

Neuromuscular activation of vastus intermedius muscle during fatiguing exercise

The purpose of this study was to investigate neuromuscular activation of the vastus intermedius (VI) muscle during fatiguing contraction. Seven healthy men performed sustained isometric knee extension exercise at 50% of maximal voluntary contraction until exhaustion. During the fatiguing task, surface electromyograms (EMGs) were recorded from four muscle components of the quadriceps femoris muscle group: VI; vastus lateralis (VL); vastus medialis (VM); and rectus femoris (RF) muscles. For the VI muscle, our recently developed technique was used. Root mean square (RMS) and median frequency (MF) of the surface EMG signal were calculated and these variables were then normalized by the value at the beginning of the task. Normalized RMS of the VI muscle resembled those of the other three muscles at all given times. At 95% of exhaustion time, normalized MF of the VI muscle was significantly higher than that of the VL muscle (p < 0.05). These results suggested that neuromuscular activation is not consistent between the VI and VL muscles at the exhaustion for isometric submaximal contraction and this could reflect the dissimilar intramuscular metabolism between these muscles.     

Skeletal muscle oxygenation during incremental exercise

The purpose of this study was to investigate the relationship between muscle oxygenation level at exhaustion and maximal oxygen uptake (VO2max) in an incremental cycling exercise. Nine male subjects took part in an incremental exhaustive cycling exercise, and then cuff occlusion was performed. Changes in oxy-(deltaHbO2) and deoxy-(deltaHb) hemoglobin concentrations in the vastus lateralis muscle were measured with a near infrared spectroscopy (NIRS). Muscle oxygenation during incremental exercise was expressed as a percentage (%Moxy) of the maximal range observed during an arterial occlusion as the lower reference point. A systematic decrease was observed in %Moxy with increasing intensity. A significant relationship was observed between %Moxy at exhaustion and VO2max (p < 0.01). We concluded that the one of the limiting factor of VO2max is the muscle oxygen diffusion capacity, and %Moxy during exercise could be one of the indexes of muscle oxygen diffusion capacity.     

Skeletal muscle metabolism during high-intensity sprint exercise is unaffected by dichloroacetate or acetate infusion.

This study investigated whether increased provision of oxidative substrate would reduce the reliance on nonoxidative ATP production and/or increase power output during maximal sprint exercise. The provision of oxidative substrate was increased at the onset of exercise by the infusion of acetate (AC; increased resting acetylcarnitine) or dichloroacetate [DCA; increased acetylcarnitine and greater activation of pyruvate dehydrogeanse (PDH-a)]. Subjects performed 10 s of maximal cycling on an isokinetic ergometer on three occasions after either DCA, AC, or saline (Con) infusion. Resting PDH-a with DCA was increased significantly over AC and Con trials (3.58 +/- 0.4 vs. 0.52 +/- 0.1 and 0.74 +/- 0.1 mmol. kg wet muscle(-1). min(-1)). DCA and AC significantly increased resting acetyl-CoA (35.2 +/- 4.4 and 22.7 +/- 2.9 vs. 10.2 +/- 1.3 micromol/kg dry muscle) and acetylcarnitine (12.9 +/- 1.4 and 11.0 +/- 1.0 vs. 3.3 +/- 0.6 mmol/kg dry muscle) over Con. Resting contents of phosphocreatine, lactate, ATP, and glycolytic intermediates were not different among trials. Average power output and total work done were not different among the three 10-s sprint trials. Postexercise, PDH-a in AC and Con trials had increased significantly but was still significantly lower than in DCA trial. Acetyl-CoA did not increase in any trial, whereas acetylcarnitine increased significantly only in DCA. Exercise caused identical decreases in ATP and phosphocreatine and identical increases in lactate, pyruvate, and glycolytic intermediates in all trials. These data suggest that there is an inability to utilize extra oxidative substrate (from either stored acetylcarnitine or increased PDH-a) during exercise at this intensity, possibly because of O(2) and/or metabolic limitations.     

Glycogen availability does not affect the TCA cycle or TAN pools during prolonged, fatiguing exercise.

The hypothesis that fatigue during prolonged exercise arises from insufficient intramuscular glycogen, which limits tricarboxylic acid cycle (TCA) activity due to reduced TCA cycle intermediates (TCAI), was tested in this experiment. Seven endurance-trained men cycled at approximately 70% of peak O(2) uptake (Vo(2 peak)) until exhaustion with low (LG) or high (HG) preexercise intramuscular glycogen content. Muscle glycogen content was lower (P < 0.05) at fatigue than at rest in both trials. However, the increase in the sum of four measured TCAI (>70% of the total TCAI pool) from rest to 15 min of exercise was not different between trials, and TCAI content was similar after 103 +/- 15 min of exercise (2.62 +/- 0.31 and 2.59 +/- 0.28 mmol/kg dry wt for LG and HG, respectively), which was the point of volitional fatigue during LG. Subjects cycled for an additional 52 +/- 9 min during HG, and although glycogen was markedly reduced (P < 0.05) during this period, no further change in the TCAI pool was observed, thus demonstrating a clear dissociation between exercise duration and the size of the TCAI pool. Neither the total adenine nucleotide pool (TAN = ATP + ADP + AMP) nor IMP was altered compared with rest in either trial, whereas creatine phosphate levels were not different when values measured at fatigue were compared with those measured after 15 min of exercise. These data demonstrate that altered glycogen availability neither compromises TCAI pool expansion nor affects the TAN pool or creatine phosphate or IMP content during prolonged exercise to fatigue. Therefore, our data do not support the concept that a decrease in muscle TCAI during prolonged exercise in humans compromises aerobic energy provision or is the cause of fatigue.     

Ultrastructural changes in skeletal muscle after fatiguing exercise.

Thoroughbred horses were exercised to fatigue at 40, 85, and 100% of their maximal oxygen consumption (VO2max) on a treadmill and completed a 1,600-m gallop on a track to identify the effect of exercise of various durations and intensities on the ultrastructure of mitochondria and sarcoplasmic reticulum (SR) from the middle gluteal muscle. The percentage of the total area occupied by mitochondria and SR increased in electron micrographs of muscle samples collected at the termination of exercise and at 30 and 60 min of recovery compared with those collected before exercise. Mitochondrial area increased 3- to 4-fold and SR area approximately 1.6-fold after exercise at the intensities greater than 40% of the VO2max. Smaller increases occurred in response to exercise at 40% of the VO2max. Areas were not different from rest in samples collected after 60 min of recovery. The reversal of ultrastructural alterations paralleled the trend toward normalization of muscle temperature, muscle pH, and the concentrations of selected muscle metabolites.     

Regulation of muscle carbohydrate metabolism during exercise.

This review examines the mechanisms that regulate muscle carbohydrate metabolism during exercise. Muscle carbohydrate utilization is regulated primarily by two factors, namely, delivery of substrate to the glycolytic pathway either from glycogenolysis or from transport of extracellular glucose into the fibers, and formation of triosephosphate by phosphofructokinase. The regulation involves the integration of the glycolytic controls with other metabolic controls and the needs of the whole muscle in meeting the physiological demand. The controls operating in the glycolytic sequence in vivo appear to couple glycolytic recruitment to signals from the rate of energy demand, the TCA cycle state, and the mitochondrial redox state so as to satisfy the major regulatory goal of maintaining the supply of ATP for tension development.     

Muscle metabolism during prolonged physical exercise in dogs

In order to provide reference data, adenine nucleotide, creatine phosphate, glycogen, glycolytic intermediates and lactate muscle contents were measured in 49 dogs under resting conditions and during prolonged physical exercise of moderate intensity performed until exhaustion. Both the resting and exercise values of the measured variables were remarkably similar to those described in human subjects, except muscle lactate content which achieved higher values during submaximal exercise in dogs than in men.     

Carnitine metabolism during prolonged exercise and recovery in humans

Lennon et al. (J. Appl. Physiol. 55: 489-495, 1983) have recently reported a large loss of muscle total carnitine (TC) after 40 min of moderate exercise. These authors have also suggested that elevations in plasma esterified carnitine (EC) were due to the release of these carnitine esters from muscle during exercise. After 10 male subjects underwent 90 min of cycle egometry we found no alteration in muscle TC from preexercise values. Plasma EC progressively increased above resting values during exercise and remained elevated above rest at 0.75 and 1.5 h into recovery. Elevations of plasma EC were largely due to a decrement in free carnitine (FC) in both conditions. Immediately postexercise the urinary fractional reabsorbsion of EC and FC were similar to that at rest. These results suggest that a net loss of TC from exercising muscle does not occur. As in other conditions marked by falling insulin concentrations, elevations in plasma EC could result from an exchange of carnitine with the hepatic carnitine pool.     

Regulation of muscle pyruvate metabolism during exercise

Pyruvate dehydrogenase and phosphoenolpyruvate carboxykinase are important enzymes in the regulation of muscle pyruvate metabolism and their in vitro measured activities have been studied in muscle from rested and exercised rats. In addition, the muscle concentration of metabolic intermediates associated with pyruvate metabolism has been measured after exercise. Phosphoenolpyruvate concentration was decreased to less than half the value found in rested muscle but pyruvate concentration did not change. This suggests an increase in the in vivo rate of conversion of phosphoenolpyruvate to pyruvate. Concentrations of malate and aspartate increased two- to threefold which suggests that oxaloacetate concentration was also increased. An increase in oxaloacetate availability would increase acetyl CoA metabolism and therefore would increase pyruvate dehydrogenase activity in vivo. The basal activity of pyruvate dehydrogenase measured in vitro increased approximately twofold after 2 hr of exercise and returned to control values 5 min after the cessation of exercise. Total pyruvate dehydrogenase activity (activated to the maximal extent) was not changed by exercise. Muscle PEPCK activity was also increased during exercise suggesting an increased rate of conversion of oxaloacetate to pyruvate to provide net oxidation of oxaloacetate and other citric acid cycle intermediates. Results of this study demonstrate that the rates of formation and metabolism of pyruvate are increased during exercise.