Energy supply and muscle fatigue in humans - P2 e P10

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Acta Physiol Scand 1998, 162, 261±266

Energy supply and muscle fatigue in humans È DERLUND K . S A H L I N , M . T O N K O N O G I and K . S O Department of Physiology and Pharmacology, Karolinska Institute and Department of Human Biology, Stockholm University College of Physical Education and Sports, Stockholm, Sweden ABSTRACT Limitations in energy supply is a classical hypothesis of muscle fatigue. The present paper reviews the evidence available from human studies that energy deficiency is an important factor in fatigue. The maximal rate of energy expenditure determined in skinned fibres is close to the rate of adenosine triphosphate (ATP) utilisation observed in vivo and data suggest that performance during short bursts of exercise (60 min) and depletion of phosphocreatine (PCr) and lactate accumulation during high-intensity exercise. When the expenditure of ATP exceeds the rate of ATP generation part of the adenine nucleotide pool is deaminated to inosine monophosphate (IMP) and ammonia (NH3). IMP can either be reaminated back to AMP or degraded further to hypoxanthine, xanthine and urate. The cellular membrane is permeable to NH3 and hypoxanthine but impermeable to phosphorylated compounds, which will remain in the cellular compartment. Increases in the degradation products of ATP can be detected in blood (hypoxanthine and NH3) or muscle (IMP and NH3) and may be used as markers of energy de®ciency. Muscle fatigue has under a variety of conditions been shown to correlate with signs of energy de®ciency, i.e. increases in muscle IMP (Sahlin & Broberg 1990) and blood hypoxanthine (Hellsten et al. 1991). How-

Correspondence: K. Sahlin, LidingoÈvaÈgen 1, Box 5626, S-114 86 Stockholm, Sweden. Ó 1998 Scandinavian Physiological Society

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ever, a correlation does not prove a causal relationship. This paper reviews the evidence available from human studies that energy de®ciency is an important factor in fatigue. P O WE R A N D CA P A CI T Y O F E N E R G E T I C P RO C E S S E S There are two inherent limits of the energetic processes: the maximum rate (power) and the amount of ATP (capacity) that can be produced (McGilvery 1973). The power and the capacity vary drastically between the energetic processes and observed peak values in human skeletal muscle are presented in Figure 1. The anaerobic processes have a higher power but a lower capacity than the aerobic processes. Therefore PCr and lactate formation will be important for short bursts of high-intensity exercise whereas the aerobic

Acta Physiol Scand 1998, 162, 261±266

processes will dominate during prolonged exercise. The relative exercise intensity (% of Vo2max) is a major determinant of the extent to which the various energetic processes are recruited and in¯uences the proportion of energy production derived from aerobic/ anaerobic processes and from CHO/fat oxidation. Other factors of importance are the availability of oxygen, availability of fuels, hormonal changes and training status. The sum of the maximal power of the ATP-generating reactions sets an upper limit of the exercise intensity, and the maximal capacity of ATP generation (at a certain exercise intensity) sets the limit of exercise duration. The crucial question is whether the limits of the metabolic processes is reached during exercise and if the resulting energy de®ciency causes fatigue. The alternative is that exercise is limited by other factors which in turn reduce energy demand and secondarily ATP generation. H I G H- I N T E N S I T Y E X E RC I S E

Figure 1 Power and capacity of the energy yielding processes in

human skeletal muscle. Values of power are based on observed values during the following conditions: PCr breakdown, 1.3 s electrical stimulation (Hultman & SjoÈholm 1983); glycolysis, 10 s cycling ( Jones et al. 1985); CHO oxidation (®lled bar), calculated from O2 extraction during two-leg cycling assuming that 72% of Vo2max (4 L min)1) is utilised by a working muscle mass of 20 kg; CHO oxidation (un®lled bar), one-leg knee extension (Andersen et al. 1985); FFA oxidation, assumed to be 50% of that of CHO oxidation (see text). Values of capacity have been derived from muscle content of PCr, glycogen (80 mmol kg)1), maximal muscle lactate accumulation and a working muscle of 20 kg. Amount of ATP that can be produced from oxidation of FFA is not limited, hence staple bar is cut off.

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The maximal rate of energy expenditure cannot exceed the activity of the ATP hydrolysing enzymes (i.e. muscle ATPase activity). Vmax of Ca activated ATPase is 3-fold higher in fast-twitch ®bres than in slow-twitch ®bres (EsseÂn et al. 1975). Myo®brillar ATPase activity has been determined during maximal static contraction in skinned human muscle ®bre to 0.10, 0.27 and 0.41 mmol L)1 s)1 in type I, IIA and IIB ®bres, respectively (Stienen et al. 1996). Assuming a Q10 of 2, 3.3 L of H2O per kg dry weight (d.wt). of muscle and 2.7 times higher energy turnover during maximal dynamic exercise than during static contraction (Potma & Stienen 1996) it can be calculated that maximal ATP expenditure is 6.5, 17.6 and 26.6 mmol ATP kg)1 d.wt. s)1 in type I, IIA and IIB ®bres, respectively. This is close to the observed rate of energy expenditure in mixed muscle during 10 s maximal cycling (15 mmol ATP kg)1 d.wt. s)1 Jones et al. 1985). Therefore, it seems plausible that the release of energy during short bursts of activity ( 60 min). Since, PCr reverses above

Figure 3 Single ®bre PCr content in vastus lateralis after prolonged exercise to fatigue. Values from 5 subjects are included. Modi®ed from Sahlin et al. (1997). Ó 1998 Scandinavian Physiological Society

Acta Physiol Scand 1998, 162, 261±266

the pre-exercise level after 5 min recovery Sahlin et al. 1997) there is a discrepancy between availability of high-energy phosphates and force. This is in contrast to high intensity exercise where recovery of force and PCr occurred in parallel. After prolonged exercise the initial rapid phase of force recovery may correspond to reversal of muscle energetics but it is clear that the remaining depression of force is related to other factors than reduced energy supply. C O N CL U D I N G RE M A RK S The hypothesis that muscle fatigue is caused by failure of the energetic processes to generate ATP at a suf®cient rate is classic. The evidence for this hypothesis is that interventions which increase the power (i.e. aerobic training) or capacity (i.e. CHO loading, creatine supplementation, glucose supplementation) of the energetic processes result in increased performance and delayed onset of fatigue. Similarly, factors that impair the energetic processes (i.e. depletion of muscle glycogen, intracellular acidosis, hypoxic conditions, reduced muscle blood ¯ow) have a negative in¯uence on performance. The evidence is however, circumstantial and a direct causal relationship remains to be established. Since muscle ATP remains practically unchanged during exercise the hypothesis that energy de®ciency causes fatigue has been questioned (Green 1991, Fitts 1994). However, this line of argument may

K Sahlin et al. á Energy supply and muscle fatigue

be too simplistic since temporal and spatial gradients of adenine nucleotides may exist in the contracting muscle and since the mechanism may be related to increases in the products of ATP hydrolysis (i.e. ADP, AMP or Pi) rather than to decreases in ATP per se. A small decrease in ATP will cause relatively large increases in ADP and AMP, due to much lower concentrations of these latter compounds. Increases in ADP has been shown to impair power output during concentric contractions (Cooke & Pate 1985, Yamashita et al. 1994). Furthermore, increases in both Pi and ADP will reduce the free energy release during ATP hydrolysis and may be of critical importance for the contraction process. This conclusion is in agreement with recent studies in isolated ®bres from mouse muscle where a sudden increase in ATP concentration resulted in a partial recovery of force (Allen et al. 1997). The present paper has focused on the limitations of energetic processes and the relation to muscle fatigue. The evidence for energy de®ciency being a determinant of fatigue is strong during high-intensity exercise. During prolonged exercise fatigue coincides with glycogen depletion and signs of energy de®ciency at the single ®bre level. However, the complexity is more pronounced during prolonged exercise and it is clear that energy de®ciency is not the sole explanation. Metabolic factors are likely to play an important role in physical performance in vivo but there is no doubt that conditions exist where fatigue cannot be explained by metabolic changes. Considering the diversity and complexity of exercise this is to be expected.

R E F E RE N CE S

Figure 4 Recovery in force and PCr after prolonged cycling to fatigue (modi®ed from Sahlin & Seger 1995 and Sahlin et al. 1997). Ó 1998 Scandinavian Physiological Society

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Ó 1998 Scandinavian Physiological Society