Lars Nybo

Cerebral perturbations provoked by prolonged exercise

This review addresses cerebral metabolic and neurohumoral alterations during prolonged exercise in humans with special focus on associations with fatigue. Global energy turnover in the brain is unaltered by the transition from rest to moderately intense exercise, apparently because exercise-induced activation of some brain regions including cortical motor areas is compensated for by reduced activity in other regions of the brain. However, strenuous exercise is associated with cerebral metabolic and neurohumoral alterations that may relate to central fatigue. Fatigue should be acknowledged as a complex phenomenon influenced by both peripheral and central factors. However, failure to drive the motorneurons adequately as a consequence of neurophysiological alterations seems to play a dominant role under some circumstances. During exercise with hyperthermia excessive accumulation of heat in the brain due to impeded heat removal by the cerebral circulation may elevate the brain temperature to >40 degrees C and impair the ability to sustain maximal motor activation. Also, when prolonged exercise results in hypoglycaemia, perceived exertion increases at the same time as the cerebral glucose uptake becomes low, and centrally mediated fatigue appears to arise as the cerebral energy turnover becomes restricted by the availability of substrates for the brain. Changes in serotonergic activity, inhibitory feed-back from the exercising muscles, elevated ammonia levels, and alterations in regional dopaminergic activity may also contribute to the impaired voluntary activation of the motorneurons after prolonged and strenuous exercise. Furthermore, central fatigue may involve depletion of cerebral glycogen stores, as signified by the observation that following exhaustive exercise the cerebral glucose uptake increases out of proportion to that of oxygen. In summary, prolonged exercise may induce homeostatic disturbances within the central nervous system (CNS) that subsequently attenuates motor activation. Therefore, strenuous exercise is a challenge not only to the cardiorespiratory and locomotive systems but also to the brain.

The Yo-Yo IR2 Test: Physiological Response, Reliability, and Application to Elite Soccer

PURPOSE To examine the physiological response, reliability, and validity of the Yo-Yo intermittent recovery level 2 test (Yo-Yo IR2). METHODS Thirteen normally trained male subjects carried out four Yo-Yo IR2 tests, an incremental treadmill test (ITT), and various sprint tests. Muscle biopsies and blood samples were obtained, and heart rate was measured before, during, and after the Yo-Yo IR2 test. Additionally, 119 Scandinavian elite soccer players carried out the Yo-Yo IR2 test on two to four occasions. RESULTS Yo-Yo IR2 performance was 591 +/- 43 (320-920) m or 4.3 (2.6-7.9) min. Test-retest coefficient of variation in distance covered was 9.6% (N = 29). Heart rate (HR) at exhaustion was 191 +/- 3 bpm, or 98 +/- 1% HRmax. Muscle lactate was 41.7 +/- 5.4 and 68.5 +/- 7.6 mmol x kg(-1) d.w. at 85 and 100% of exhaustion time, respectively, with corresponding muscle CP values of 40.4 +/- 5.2 and 29.4 +/- 4.7 mmol x kg(-1) d.w. Peak blood lactate was 13.6 +/- 0.5 mM. Yo-Yo IR2 performance was correlated to ITT performance (r = 0.74, P < 0.05) and VO2max (r = 0.56, P < 0.05) but not to 30- and 50-m sprint performance. Yo-Yo IR2 performance was better (P < 0.05) for international elite soccer players than for moderate elite players (1059 +/- 35 vs 771 +/- 26 m) and better (P < 0.05) for central defenders (N = 21), fullbacks (N = 20), and midfielders (N = 48) than for goalkeepers (N = 6) and attackers (N = 24). Fifteen elite soccer players improved (P < 0.05) Yo-Yo IR2 performance by 42 +/- 8% during 8 wk of preseasonal training. CONCLUSION This study demonstrates that the Yo-Yo IR2 test is reproducible and can be used to evaluate an athletes ability to perform intense intermittent exercise with a high rate of aerobic and anaerobic energy turnover. Specifically, the Yo-Yo IR2 test was shown to be a sensitive tool to differentiate between intermittent exercise performance of soccer players in different seasonal periods and at different competitive levels and playing positions.

Inadequate heat release from the human brain during prolonged exercise with hyperthermia.

Brain temperature appears to be an important factor affecting motor activity, but it is not known to what extent brain temperature increases during prolonged exercise in humans. Cerebral heat exchange was therefore evaluated in seven males during exercise with and without hyperthermia. Middle cerebral artery mean blood velocity (MCA Vmean) was continuously monitored while global cerebral blood flow (CBF) and cerebral energy turnover were determined at the end of the two exercise trials in three subjects. The arterial to venous temperature difference across the brain (v‐aDtemp) was determined via thermocouples placed in the internal jugular vein and in the aorta. The jugular venous blood temperature was always higher than that of the arterial blood, demonstrating that heat was released via the CBF during the normothermic as well as the hyperthermic exercise condition. However, heat removal via the jugular venous blood was 30 ± 6 % lower during hyperthermia compared to the control trial. The reduced heat removal from the brain was mainly a result of a 20 ± 6 % lower CBF (22 ± 9 % reduction in MCA Vmean), because the v‐aDtemp was not significantly different in the hyperthermic (0.20 ± 0.05 °C) compared to the control trial (0.22 ± 0.05 °C). During hyperthermia, the impaired heat removal via the blood was combined with a 7 ± 2 % higher heat production in the brain and heat was consequently stored in the brain at a rate of 0.20 ± 0.06 J g−1 min−1. The present results indicate that the average brain temperature is at least 0.2 °C higher than that of the body core during exercise with or without hyperthermia.

Muscle temperature and sprint performance during soccer matches – beneficial effect of re‐warm‐up at half‐time

The relationship between quadriceps muscle temperature (Tm) and sprint performance was evaluated during soccer matches in 25 competitive players. In one game, Tm was determined frequently (n=9). In another game, eight players performed low‐intensity activities at half‐time (re‐warm‐up, (RW), whereas another eight players recovered passively (CON). Tm was 36.0±0.2 °C at rest and increased (P<0.05) to 39.4±0.2 °C before the game and remained unaltered during the first half. At half‐time, Tm decreased (P<0.05) to 37.4±0.2 °C, but increased (P<0.05) to 39.2±°C during the second half. In CON and RW, Tm and core temperature (Tc) were similar before and after the first half, but 2.1±0.1 and 0.9±0.1 °C higher (P<0.05), respectively, in RW prior to the second half. At the onset of the second half, the sprint performance was reduced (P<0.05) by 2.4% in CON, but unchanged in RW. The decrease in Tm was correlated to the decrease in performance (r=0.60, P<0.05, n=16). This study demonstrates that in soccer, the decline in Tm and Tc during half‐time is associated with a lowered sprint capacity at the onset of the second half, whereas sprint performance is maintained when low‐intensity activities preserve muscle temperature.

Middle cerebral artery blood velocity is reduced with hyperthermia during prolonged exercise in humans.

1 In the present study we examined the effect of hyperthermia on the middle cerebral artery mean blood velocity (MCA Vmean) during prolonged exercise. We predicted that the cerebral circulation would be impaired when hyperthermia is present during exercise and assumed that this could be observed as a reduced MCA Vmean. 2 Eight endurance trained men (maximum oxygen uptake (V̇O2,max) 70 ± 1 ml min−1 kg−1 (mean ±s.e.m.)) performed two exercise trials at 57 % of V̇O2,max on a cycle ergometer in a hot (40 °C; hyperthermic trial) and in a thermoneutral environment (18 °C; control trial). In the hyperthermic trial, the oesophageal temperature increased throughout the exercise period reaching a peak value of 40.0 ± 0.1 °C at exhaustion after 53 ± 4 min of exercise. In the control trial, exercise was maintained for 1 h without any signs of fatigue and with core temperature stabilised at 37.8 ± 0.1 °C after ≈15 min of exercise. 3 Concomitant with the development of hyperthermia, MCA Vmean declined by 26 ± 3 % from 73 ± 4 cm s−1 at the beginning of exercise to 54 ± 4 cm s−1 at exhaustion (P < 0.001). In contrast, MCA Vmean remained unchanged at 70‐72 cm s−1 throughout the 1 h control trial. 4 When individually determined regression lines for MCA Vmean and arterial carbon dioxide pressure (Pa,CO2) obtained during preliminary exercise tests were used to account for the differences in Pa,CO2 between the hyperthermic and control trial, it appeared that more than half of the reduction in MCA Vmean (56 ± 8 %) was related to a hyperventilation‐induced drop in Pa,CO2. Declining cardiac output and arterial blood pressure accounted for the remaining part of the hyperthermia‐induced reduction in MCA Vmean. 5 The present results demonstrate that the development of hyperthermia during prolonged exercise is associated with a marked reduction in MCA Vmean.

Capillary-oxygenation-level-dependent near-infrared spectrometry in frontal lobe of humans

Brain function requires oxygen and maintenance of brain capillary oxygenation is important. We evaluated how faithfully frontal lobe near-infrared spectroscopy (NIRS) follows haemoglobin saturation (SCap) and how calculated mitochondrial oxygen tension (PMitoO2) influences motor performance. Twelve healthy subjects (20 to 29 years), supine and seated, inhaled O2 air-mixtures (10% to 100%) with and without added 5% carbon dioxide and during hyperventilation. Two measures of frontal lobe oxygenation by NIRS (NIRO-200 and INVOS) were compared with capillary oxygen saturation (SCap) as calculated from the O2 content of brachial arterial and right internal jugular venous blood. At control SCap (78% ± 4%; mean ± s.d.) was halfway between the arterial (98% ± 1%) and jugular venous oxygenation (SVO2; 61% ± 6%). Both NIRS devices monitored SCap (P < 0.001) within ~5% as SvO2 increased from 39% ± 5% to 79% ± 7% with an increase in the transcranial ultrasound Doppler determined middle cerebral artery flow velocity from 29 ± 8 to 65 ± 15 cm/sec. When SCap fell below ~70% with reduced flow and inspired oxygen tension, PMitoO2 decreased (P < 0.001) and brain lactate release increased concomitantly (P < 0.001). Handgrip strength correlated with the measured (NIRS) and calculated capillary oxygenation values as well as with PMitoO2 (r > 0.74; P < 0.05). These results show that NIRS is an adequate cerebral capillaryoxygenation-level-dependent (COLD) measure during manipulation of cerebral blood flow or inspired oxygen tension, or both, and suggest that motor performance correlates with the frontal lobe COLD signal.

Cerebral changes during exercise in the heat.

AbstractThis review focuses on cerebral changes during combined exercise and heat stress, and their relation to fatigue. Dynamic exercise can elevate the core temperature rapidly and high internal body temperatures seem to be an independent cause of fatigue during exercise in hot environments. Thus, in laboratory settings, trained participants become exhausted when they reach a core temperature of ∼40°C. The observation that exercise-induced hyperthermia reduces the central activation percentage during maximal isometricmuscle contractions supports the idea that central fatigue is involved in the aetiology of hyperthermia-induced fatigue. Thus, hyperthermia does not impair the ability of the muscles to generate force, but sustained force production is lowered as a consequence of a reduced neural drive from the CNS. During ongoing dynamic exercise in hot environments, there is a gradual slowing of the electroencephalogram (EEG) whereas hyperthermia does not affect the electromyogram. The frequency shift of the EEG is highly correlated with the participants’ perception of exertion, which furthermore may indicate that alterations in cerebral activity, rather than peripheral fatigue, are associated with the hyperthermia-induced development of fatigue. Cerebral blood flow is reduced by approximately 20% during exercise with hyperthermia due to hyperventilation,which causes a lowering of the arterial CO2 pressure. However, in spite of the reduced blood flow, cerebral glucose and oxygen uptake does not seem to be impaired. Removal of heat from the brain is also an important function of the cerebral blood flow and the lowered perfusion of the brain during exercise and heat stress appears to reduce heat removal by the venous blood. Heat is consequently stored in the brain. The causal relationship between the circulatory changes, the EEG changes and the hyperthermia-induced central fatigue is at the present not well understood and future studies should focus on this aspect.

Inadequate cerebral oxygen delivery and central fatigue during strenuous exercise

Under resting conditions, the brain is protected against hypoxia because cerebral blood flow increases when the arterial oxygen tension becomes low. However, during strenuous exercise, hyperventilation lowers the arterial carbon dioxide tension and blunts the increase in cerebral blood flow, which can lead to an inadequate oxygen delivery to the brain and contribute to the development of fatigue.

Recreational soccer is an effective health-promoting activity for untrained men

To examine the effects of regular participation in recreational soccer on health profile, 36 healthy untrained Danish men aged 20–43 years were randomised into a soccer group (SO; n = 13), a running group (RU; n = 12) and a control group (CO; n = 11). Training was performed for 1 h two or three times per week for 12 weeks; at an average heart rate of 82% (SEM 2%) and 82% (1%) of HRmax for SO and RU, respectively. During the 12 week period, maximal oxygen uptake increased (p<0.05) by 13% (3%) and 8% (3%) in SO and RU, respectively. In SO, systolic and diastolic blood pressure were reduced (p<0.05) from 130 (2) to 122 (2) mm Hg and from 77 (2) to 72 (2) mm Hg, respectively, after 12 weeks, with similar decreases observed for RU. After the 12 weeks of training, fat mass was 3.0% (2.7 (0.6) kg) and 1.8% (1.8 (0.4) kg) lower (p<0.05) for SO and RU, respectively. Only SO had an increase in lean body mass (1.7 (0.4) kg, p<0.05), an increase in lower extremity bone mass (41 (8) g, p<0.05), a decrease in LDL-cholesterol (2.7 (0.2) to 2.3 (0.2) mmol/l; p<0.05) and an increase (p<0.05) in fat oxidation during running at 9.5 km/h. The number of capillaries per muscle fibre was 23% (4%) and 16% (7%) higher (p<0.05) in SO and RU, respectively, after 12 weeks. No changes in any of the measured variables were observed for CO. In conclusion, participation in regular recreational soccer training, organised as small-sided drills, has significant beneficial effects on health profile and physical capacity for untrained men, and in some aspects it is superior to frequent moderate-intensity running.

Cns Fatigue and Prolonged Exercise: Effect of Glucose Supplementation

INTRODUCTION Ingestion of carbohydrates during prolonged exercise may improve endurance, whereas an insufficient supply of glucose results in hypoglycemia and fatigue. Fatigue, defined as a loss of force-generating capacity, may develop for a variety of reasons and involve both central and peripheral factors. This study investigated whether CNS activation of the skeletal muscles was affected by prolonged exercise with or without glucose supplementation. METHODS Voluntary force production and central activation ratios, assessed by the twitch interpolation technique, were determined during a 2-min sustained maximal knee extension in eight endurance-trained males in a baseline condition and immediately after 3 h of cycling randomized to be with or without glucose supplementation. RESULTS The exercise bout without glucose supplementation (placebo trial) reduced the blood glucose concentration from 4.5 +/- 0.2 to 3.0 +/- 0.2 mM, whereas blood glucose homeostasis was maintained during the glucose trial. The average force during the sustained maximal voluntary muscle contraction was 248 +/- 23 N at baseline, 222 +/- 20 N in the glucose trial, and 197 +/- 21 N in the placebo trial (P < 0.05 between conditions). In the placebo trial, the lowered force production was accompanied by a reduced level of CNS activation compared with the other two conditions (P < 0.05), whereas the central activation ratios were similar in the glucose trial as compared with baseline. CONCLUSION Exercise-induced hypoglycemia attenuates CNS activation during a sustained maximal muscle contraction, whereas central activation appears to be unaffected by 3 h of moderately intense exercise in endurance-trained athletes when euglycemia is maintained by carbohydrate ingestion.