Muscle fatigue is an exercise-induced reduction in maximal voluntary muscle force. It may arise not only because of peripheral changes at the level of the muscle, but also because the central nervous system fails to drive the motoneurons adequately. Evidence for “central” fatigue and the neural mechanisms underlying it are reviewed, together with its terminology and the methods used to reveal it. Much data suggest that voluntary activation of human motoneurons and muscle fibers is suboptimal and thus maximal voluntary force is commonly less than true maximal force. Hence, maximal voluntary strength can often be below true maximal muscle force. The technique of twitch interpolation has helped to reveal the changes in drive to motoneurons during fatigue. Voluntary activation usually diminishes during maximal voluntary isometric tasks, that is central fatigue develops, and motor unit firing rates decline. Transcranial magnetic stimulation over the motor cortex during fatiguing exercise has revealed focal cha...

Spinal and Supraspinal Factors in Human Muscle Fatigue

Repeated, intense use of muscles leads to a decline in performance known as muscle fatigue. Many muscle properties change during fatigue including the action potential, extracellular and intracellular ions, and many intracellular metabolites. A range of mechanisms have been identified that contribute to the decline of performance. The traditional explanation, accumulation of intracellular lactate and hydrogen ions causing impaired function of the contractile proteins, is probably of limited importance in mammals. Alternative explanations that will be considered are the effects of ionic changes on the action potential, failure of SR Ca2+ release by various mechanisms, and the effects of reactive oxygen species. Many different activities lead to fatigue, and an important challenge is to identify the various mechanisms that contribute under different circumstances. Most of the mechanistic studies of fatigue are on isolated animal tissues, and another major challenge is to use the knowledge generated in these studies to identify the mechanisms of fatigue in intact animals and particularly in human diseases.

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Skeletal Muscle Fatigue: Cellular Mechanisms

Regularly performed endurance exercise induces major adaptations in skeletal muscle. These include increases in the mitochondrial content and respiratory capacity of the muscle fibers. As a consequence of the increase in mitochondria, exercise of the same intensity results in a disturbance in homeostasis that is smaller in trained than in untrained muscles. The major metabolic consequences of the adaptations of muscle to endurance exercise are a slower utilization of muscle glycogen and blood glucose, a greater reliance on fat oxidation, and less lactate production during exercise of a given intensity. These adaptations play an important role in the large increase in the ability to perform prolonged strenuous exercise that occurs in response to endurance exercise training.

Adaptations of skeletal muscle to endurance exercise and their metabolic consequences

The effect of insulin on the disposal of intravenous glucose was examined employing the euglycemic insulin clamp technique in 24 normal subjects. When the plasma insulin concentration was raised by approximately 100 μU/ml, total glucose metabolism rose to 6.63 ± 0.38 mg/kg · min. Basal splanchnic (hepatic venous catheter technique) glucose production, 2.00 increased only slightly. These results suggest that the ability of higher doses of insulin to further stimulate glucose metabolism is primarily the result of increased glucose storage by peripheral tissues, most likely muscle. 0.15 ± mg/kg · min, reverted to a small net glucose uptake which averaged 0.33 mg/kg · min over the ensuing 2 h. This represented only 5% of the total glucose metabolized. In contrast, leg (femoral venous catheterization) glucose uptake rose from 1.18 ± 0.14 to 8.40 ± 1.06 mg/kg of leg wt. per min. If all muscles in the body respond similarly to those in the leg, muscle would account for 85% of the total glucose metabolism. To determine the relative contributions of glucose oxidation versus glucose storage by peripheral tissues following hyperinsulinemia, we performed euglycemic insulin clamp studies in combination with indirect calorimetry. Basal glucose oxidation, 1.21 ± 0.10 mg/kg min, rose to 2.28 ± 0.16 (P

The Effect of Insulin on the Disposal of Intravenous Glucose: Results from Indirect Calorimetry and Hepatic and Femoral Venous Catheterization

The muscle glycogen content of the quadriceps femoris muscle was determined in 9 healthy subjects with the aid of the needle biopsy technique. The glycogen content could be varied in the individual subjects by instituting different diets after exhaustion of the glycogen store by hard exercise. Thus, the glycogen content after a fat ± protein (P) and a carbohydrate-rich (C) diet varied maximally from 0.6 g/100g muscle to 4.7 g. In all subjects, the glycogen content after the C diet was higher than the normal range for muscle glycogen, determined after the mixed (M) diet. After each diet period, the subjects worked on a bicycle ergometer at a work load corresponding to 75 per cent of their maximal O2 uptake, to complete exhaustion. The average work time was 59, 126 and 189 min after diets P, M and C, and a good correlation was noted between work time and the initial muscle glycogen content. The total carbohydrate utilization during the work periods (54–798 g) was well correlated to the decrease in glycogen content. It is therefore concluded that the glycogen content of the working muscle is a determinant for the capacity to perform long-term heavy exercise. Moreover, it has been shown that the glycogen content and, consequently, the long-term work capacity can be appreciably varied by instituting different diets after glycogen depletion.

Diet, Muscle Glycogen and Physical Performance

10 well trained and 10 untrained subjects worked to complete exhaustion on a bicycle ergometer with work loads averaging 77 (76–87) per cent of their individual maximal aerobic power. Determinations of glycogen used by working muscles (biopsy of lateral portion of the quadriceps femoris muscles) and of combusted carbohydrate (Vo2 and RQ) were performed at certain intervals from the start of work to exhaustion. At a combustion rate of about 3 g carbohydrate per minute (RQ around 0.9 or higher) and at average values for glycogen in resting muscle of 1.6 (1.1–2.5)g/100 wet muscle, the effective work time was around 85 min for the untrained and 90 min for the trained subjects. At the end of the exhaustive exercise the glycogen content averaged 0.06 g in the untrained and 0.12 g/100 g wet muscle in the trained subjects. A close relationship between utilized glycogen and combusted carbohydrate was found, and it seems highly probable that at high relative workloads primarily the glycogen stores in the exercising muscles will limit the capacity for prolonged strenuous work.

Muscle glycogen during prolonged severe exercise.

IT is well known that glycogen is utilized during muscular work, but there is very little information available about the resynthesis of glycogen after exhaustive exercise. Goldstein1 has shown that a humoral factor, which decreases the blood glucose concentration, is released during exercise. Furthermore, it is known that the insulin requirement decreases in diabetic subjects during exercise.

Muscle Glycogen Synthesis after Exercise : an Enhancing Factor localized to the Muscle Cells in Man

The time course of phosphorylcreatine (PC) resynthesis in the human m. quadriceps femoris was studied during recovery from exhaustive dynamic exercise and from isometric contraction sustained to fatigue. The immediate postexercise muscle PC content after either form of exercise was 15-16% of the resting muscle content. The time course of PC resynthesis during recovery was biphasic exhibiting a fast and slow recovery component. The half-time for the fast component was 21-22s but this accounted for a smaller fraction of the total PC restored during recovery from the isometric contraction than after the dynamic exercise. The half-time for the slow component was in each case more than 170 s. After 2 and 4 min recovery the total amount of PC resynthesized after the isometric exercise were significantly lower than from the dynamic exercise. Occlusion of the circulation of the quadriceps completely abolished the resynthesis of PC. Restoration of resynthesis occurred only after release of occlusion.

The time course of phosphorylcreatine resynthesis during recovery of the quadriceps muscle in man

Analyzes were made on muscle samples taken from the lateral part of the m quadriceps femoris of man (lactate, pyruvate, and pH) on venous blood (lactate, pyruvate) and on capillary blood (pH) Samples were taken at rest, immediately after termination of dynamic exercise and during 20 min recovery from exhaustive dynamic exercise Muscle pH decreases from 708 atrest to 660 at exhaustion Decrease in muscle pH was linearly related to muscle content of lactate + pyruvate The relationship was slightly different from what has been obtained after isometric exercise and this difference was ascribed to acid-base exchange with the blood during dynamic exercise Lactate content was highly elevated in muscle after exercise and the concentration was 2-3 times higher than in blood Pyruvate content was, however, only slightly higher than that at rest During recovery, lactate content of muscle decreased exponentially with respect to time, whereas pyruvate content increased The half-time of lactate decrease was 95 min From the lactate dehydrogenase equilibrium relative values on NADH/NAD ratio could be calculated It was found that NADH/NAD was highly increased after exercise and that it had not returned to the basal value after 20 min recovery

Eric Hultman

Papers

Diet, Muscle Glycogen and Physical Performance

Muscle glycogen during prolonged severe exercise.

Muscle Glycogen Synthesis after Exercise : an Enhancing Factor localized to the Muscle Cells in Man

The time course of phosphorylcreatine resynthesis during recovery of the quadriceps muscle in man

Lactate content and pH in muscle obtained after dynamic exercise.