Ole M. Sejersted

Biochemical correlates of fatigue

SummaryMuscle fatigue, defined as a decreased force generating capacity, develops gradually during exercise and is distinct from exhaustion, which occurs when the required force or exercise intensity can no longer be maintained. We have reviewed several biochemical and ionic changes reported to occur in exercising muscle, and analysed the possible effects these changes may have on the electrical and contractile properties of the muscle. There is no evidence that substrate depletion can account for the decreased force generating capacity, but this factor may be important for the rate of energy turnover and be a major determinant for endurance. Increased concentration of inorganic phosphate and hydrogen ions will depress the force generating capacity, but since fatigue can develop gradually without accumulation of these ions they can only be important when aerobic ATP production is insufficient to support the contractions. Evidence is presented showing that a disturbed balance of K+ alone might cause depolarisation block at high stimulation frequencies, but extracellular K+ accumulation does not increase gradually during prolonged dynamic or static exercise, and is therefore not closely related to fatigue. The repeated release of Ca2+ from the sarcoplasmic reticulum (SR) during muscular activity is suggested of Ca2+ by the mitochondria, increasing with stimulation frequency and duration and possibly also deteriorating mitochondrial function. We therefore speculate that decreased Ca2+ availability for release from SR might contribute to a gradual decline in force generating capacity during all types of exercise.

Effect of intensity of exercise on excess postexercise O2 consumption

After exercise, there is an increase in O2 consumption termed the excess postexercise O2 consumption (EPOC). In this study, we have examined the effect of exercise intensity on the time course and magnitude of EPOC. Six healthy male subjects exercised on separate days for 80 minutes at 29%, 50%, and 75% of maximal O2 uptake (VO2max) on a cycle ergometer. O2 uptake, R value, and rectal temperature were measured while the subjects rested in bed for 14 hours postexercise, and the results were compared with those of an identical control experiment without exercise. An increase in O2 uptake lasting for 0.3 +/- 0.1 hour (29% exercise), 3.3 +/- 0.7 hour (50%) and 10.5 +/- 1.6 hour (75%) was observed. EPOC was 1.3 +/- 0.46 I(29%), 5.7 +/- 1.7 I (50%), and 30.1 +/- 6.4 I (75%). There was an exponential relationship between exercise intensity and total EPOC, both during the first 2 hours and the next 5 hours of recovery. Hence, prolonged exercise at intensities above 40% to 50% of VO2max is required in order to trigger the metabolic processes that are responsible for the prolonged EPOC component extending beyond 2 hours postexercise.

Effect of exercise intensity on potassium balance in muscle and blood of man.

1. The rise of plasma [K+] during high intensity exercise is due to an initially rapid loss of K+ from the exercising muscle to the circulation. The K+ loss is primarily governed by the balance between K+ efflux rate from the muscle cells and the reuptake rate. It has been assumed that the reuptake rate is proportional to [K+] in the femoral vein ([K+]fv) during short‐lasting uphill running, but this may not hold true for other types and durations of exercise. 2. In four subjects, initial rates of increase and decay of [K+]fv at start and end of bicycle exercise were quantified by means of K(+)‐sensitive electrodes inserted into the femoral vein. Responses to exercise intensities between 90 and 440 W were examined. Both the initial rate of rise and the rate of decay of [K+]fv were linearly related to power. 3. In six subjects, exercising at 60, 85 and 110% of maximal oxygen uptake, blood was obtained from the femoral artery and vein. The veno‐arterial concentration difference for K+ across the exercising leg decayed with half‐times of about 3 min at all exercise levels and became not significantly different from zero at low powers. This fits with a good match between K+ efflux and reuptake rates at the cellular level. 4. Arterial plasma [K+] ([K+]a) rose faster with increasing exercise intensity, reaching peak values of 5.7 +/‐ 0.1, 6.0 +/‐ 0.2 and 8.0 +/‐ 0.2 mmol l‐1. [K+]a fell again over the subsequent 5 min at the lowest intensity in spite of significant loss of muscle K+. Hence, released K+ was redistributed to other compartments outside the vascular bed. 5. While K+ loss increased linearly with increasing power, [K+]a showed a curvilinear relationship. Thus redistribution of K+ is less efficient at high intensities. [K+]a correlated better with relative work load than with absolute work load. 6. Reuptake of K+ after the end of the high intensity bout of exercise caused [K+]a to fall with a half‐time of 31 s. The rate of K+ reuptake in the exercising muscle was not proportional to [K+]a or [K+]fv. However, at the level of the muscle cell, the rate of K+ reuptake was probably inversely related to intracellular [K+].

K+ shifts of skeletal muscle during stepwise bicycle exercise with and without beta‐adrenoceptor blockade.

1. K+ efflux rate and control of K+ reuptake rate in exercising muscle cells was examined in six healthy female volunteers. 2. A K(+)‐selective electrode in the femoral vein continuously monitored K+ concentration ([K+]fv) during bicycling. Power was increased stepwise 5‐6 times by 30‐40 W every fourth minute until exhaustion before and after I.V. administration of propranolol. Leg blood flow was measured by bolus injections of Cardiogreen. 3. [K+]fv increased from about 4.3 to 6.8 mmol l‐1 at exhaustion both before and after propranolol administration, but after drug infusion endurance was reduced from 22.2 +/‐ 0.6 to 19.7 +/‐ 1.1 min, so [K+]fv rose more rapidly. 4. The exercise‐induced efflux rate of K+ from the muscle cells was estimated to be about 11 mumol kg‐1s‐1 at exhaustion both before and after propranolol administration. 5. As an indicator of rate of net loss of K+ from the leg, veno‐arterial concentration differences ([K+]fv‐a) during first, fourth and fifth power increments were high after 15 and 40 s, but declined toward the end of each power step. Propranolol accentuated [K+]fv‐a only after 15 and 40 s of the first and fourth increments. 6. The exercise‐induced increase in reuptake rate of K+ in the muscle, estimated at exhaustion, was not significantly changed by propranolol and was about 10 mumol kg‐1s‐1, corresponding to about 15% of maximum Na(+)‐K+ pump capacity in man. 7. Extracellular accumulation and loss of K+ from muscle during bicycle exercise is due to Na(+)‐K+ pump lag. The higher [K+]fv during propranolol is mainly due to impaired redistribution outside the exercising muscles. In addition at low powers, beta‐adrenoceptor blockade caused a transiently increased net loss due to an accentuated Na(+)‐K+ pump lag.

Occupational muscle pain and injury; scientific challenge

Occupational muscle pain and injury was the topic of a Nordic Symposium held in Norway, October 1986. This issue contains 13 contributions to the symposium, some presenting new material, others being reviews. As organizers of the Symposium we are very much obliged to the Editors of the European Journal of Applied Physiology and Occupational Physiology for judging the topic important enough to deserve publication.

Changes in Na+, K(+)-adenosinetriphosphatase, citrate synthase and K+ in sheep skeletal muscle during immobilization and remobilization.

The K+ balance and muscle activity seem to interact in a complex way with regard to regulating the muscle density of Na+-K+ pumps. The effect of immobilization was examined in ten sheep that had low muscle K+ content. Three additional sheep served as untreated controls. After being brought from pasture to sheep stalls one hindlimb was immobilized in a plaster splint for 9 weeks, and in five of the animals remobilization was carried out for a further 9 weeks. The weight bearing of the leg in plaster was recorded by a force plate. Open muscle biopsies from the vastus lateralis muscle were obtained before the study, after 9 weeks of immobilization, and after another 9 weeks of remobilization. The Na+-K+ pump density was measured as [3H]-ouabain binding to intact tissue, and citrate synthase activity was measured in tissue homogenate. The tissue content of K+ was measured in fat-free dried tissue. Muscle K+ content increased linearly by almost 70% through the 18-week period independent of intervention. Immobilization reduced thigh circumference by 8% (P < 0.05) . A slight decrease in the area of type I fibres at 9 weeks and a slight increase at 18-weeks was found. The [3H]-ouabain binding was reduced by 39% and 22% in the immobilized and control legs, respectively, whereas citrate synthase activity was reduced by about 30% in both legs after 9 weeks of immobilization. During remobilization both the [3H]-ouabain binding and the citrate synthase activity increased to the same level as in the control animals. The plaster cast significantly reduced mass bearing of the immobilized leg, and a corresponding reduction in muscle activity must be assumed to have occurred in both legs as judged from citrate synthase activity. We concluded from this study that the reduction in the [3H]-ouabain binding during immobilization independent of an increase in muscle K+ content points to muscle activity as a strong stimulus for control of Na+-K+ bump density.

Atrial natriuretic peptide in plasma after prolonged physical strain, energy deficiency and sleep deprivation

SummaryPlasma concentrations of atrial natriuretic peptide (ANP) were investigated daily in 16 male cadets during a 6-day military training course with continuous heavy physical activities, sleep and energy deficiency (course 1). At the end of another similar course (course 11) 15 cadets were studied during 30-min cycle exercise at 50% maximal oxygen uptake with and without glucose infusion. A small, but not significant increase was found in the plasma concentrations of ANP during course I from 9.6 (SEM 1.1) pmol·l−1 in the control experiment to 11.1 (SEM 0.5) pmol·l−1 on day 5. During course II a small but significant increase was found from 7.8 (SEM 0.5) pmol·l−1 in the control experiment to 9.1 (SEM 0.5) pmol·l−1 at the end of the course. Plasma osmolality and chloride concentration decreased during the course. During the exercise test a significant increase was seen in ANP concentration from 8.2 (SEM 0.8) to 13.1 (SEM 2.0) pmol·l−1 in the control experiment and from 9.4 (SEM 0.7) to 13.5 (SEM 1.2) pmol·l−1 during the course. This response was attenuated by glucose infusion, an effect which may have been due to an exercise induced increase in plasma chloride concentration being abolished. In contrast, the potassium concentration response to exercise was increased during the course but unaffected by glucose infusion. In conclusion, the large increases in endogenous plasma catecholamine concentration shown to take place during previous courses were not reflected in the plasma concentrations of ANP, indicating only a moderate cardiac stress or no cardiac work overload during such courses.