Secher NH, Seifert T, Van Lieshout JJ. Cerebral blood flow and metabolism during exercise, implications for fatigue. J Appl Physiol 104: 306 -314, 2008. First published October 25, 2007 doi:10.1152/japplphysiol.00853.2007.-During exercise: the Kety-Schmidt-determined cerebral blood flow (CBF) does not change because the jugular vein is collapsed in the upright position. In contrast, when CBF is evaluated by 133 Xe clearance, by flow in the internal carotid artery, or by flow velocity in basal cerebral arteries, a ϳ25% increase is detected with a parallel increase in metabolism. During activation, an increase in cerebral O 2 supply is required because there is no capillary recruitment within the brain and increased metabolism becomes dependent on an enhanced gradient for oxygen diffusion. During maximal whole body exercise, however, cerebral oxygenation decreases because of eventual arterial desaturation and marked hyperventilation-related hypocapnia of consequence for CBF. Reduced cerebral oxygenation affects recruitment of motor units, and supplemental O 2 enhances cerebral oxygenation and work capacity without effects on muscle oxygenation. Also, the work of breathing and the increasing temperature of the brain during exercise are of importance for the development of so-called central fatigue. During prolonged exercise, the perceived exertion is related to accumulation of ammonia in the brain, and data support the theory that glycogen depletion in astrocytes limits the ability of the brain to accelerate its metabolism during activation. The release of interleukin-6 from the brain when exercise is prolonged may represent a signaling pathway in matching the metabolic response of the brain. Preliminary data suggest a coupling between the circulatory and metabolic perturbations in the brain during strenuous exercise and the ability of the brain to access slow-twitch muscle fiber populations. ammonium; central fatigue; cerebral blood flow; cerebral metabolic ratio; glucose; glycogen; lactate; oxygen; temperature DURING EXERCISE, THERE IS hyperbolic relationship between work intensity and endurance, and A. V. Hill used the relationship to demonstrate that energy turnover can be taken to represent a continuous provision of energy supplemented by an energy store (56). Yet, it is the brain that makes the decision when to slow down or to stop exercise, and from that perspective fatigue is of central origin. Obviously, cerebral metabolism becomes affected if exercise has a duration that lowers blood glucose (74), and, equally, the low O 2 tension faced during mountaineering (47) affects brain function. Perturbation of cerebral metabolism is, however, not restricted to situations where the arterial glucose and O 2 levels are reduced. Recent investigations (3,65,70,90) indicate that also at sea level maximal exercise may be associated with so-called central fatigue as indicated by lower voluntary activation than the force elicited during evoked contractions.The purpose of this review is to address cerebral metabolism in ...

During insulin stimulation whole body glucose uptake is increased in trained compared with untrained humans. However, it is not known which tissue is responsible. Seven young male subjects bicycle trained one leg for 10 wk at 70% of maximal O2 consumption (VO2max). Sixteen hours after last exercise bout, a three-step euglycemic hyperinsulinemic clamp (clamp 1) was performed (insulin levels, means +/- SE: 9 +/- 1, 53 +/- 3, 174 +/- 5, and 2,323 +/- 80 was microU/ml), with measurement of arteriovenous differences and blood flow in both legs. After 6 days of detraining subjects were restudied, having exercised the untrained leg 16 h before. VO2max for trained (T) and untrained (UT) legs was 52 +/- 2 vs. 44 +/- 2 ml.min-1.kg-1 (P < 0.05). In clamp 1 glucose uptake in T and UT legs was 1.0 +/- 0.2 vs. 0.5 +/- 0.1 mg.min-1.kg-1 (basal), 9.7 +/- 2.3 vs. 6.7 +/- 1.7 (P < 0.05) (step I), 19.2 +/- 2.8 vs. 14.3 +/- 2.0 (P < 0.05) (step II), and 22.8 +/- 2.3 vs. 18.6 +/- 2.2 (P < 0.05) (step III). During insulin infusion lactate release (P < 0.05) [8.9 +/- 1.8 vs. 2.9 +/- 0.9 mumol.min-1.kg-1 (step I), 24.6 +/- 3.1 vs. 12.5 +/- 2.6 (step III)] and glycogen storage (P < 0.1) calculated by indirect calorimetry [6.7 +/- 2.3 vs. 5.0 +/- 1.7 mg.min-1.kg-1 (step I), 16.8 +/- 2.1 vs. 14.1 +/- 1.8 (step III)] were always higher in T than in UT legs. Release of glycerol, free fatty acids, and tyrosine and clearance of insulin were not influenced by training. Insulin-mediated glucose uptake was not increased after detraining or a single bout of exercise. In conclusion, training increases sensitivity and responsiveness of insulin-mediated glucose uptake in human muscle by local mechanisms. Glycolysis and glycogen storage are equally enhanced. The training effect represents a genuine adaptation to repeated exercise but is short lived. Insulin clearance in muscle is not influenced by training.

During insulin stimulation whole body glucose uptake is increased in trained compared with untrained humans. However, it is not known which tissue is responsible. Seven young male subjects bicycle trained one leg for 10 wk at 70% of maximal O2 consumption (VO2max). Sixteen hours after last exercise bout, a three-step euglycemic hyperinsulinemic clamp (clamp 1) was performed (insulin levels, means +/- SE: 9 +/- 1, 53 +/- 3, 174 +/- 5, and 2,323 +/- 80 was microU/ml), with measurement of arteriovenous differences and blood flow in both legs. After 6 days of detraining subjects were restudied, having exercised the untrained leg 16 h before. VO2max for trained (T) and untrained (UT) legs was 52 +/- 2 vs. 44 +/- 2 ml.min-1.kg-1 (P < 0.05). In clamp 1 glucose uptake in T and UT legs was 1.0 +/- 0.2 vs. 0.5 +/- 0.1 mg.min-1.kg-1 (basal), 9.7 +/- 2.3 vs. 6.7 +/- 1.7 (P < 0.05) (step I), 19.2 +/- 2.8 vs. 14.3 +/- 2.0 (P < 0.05) (step II), and 22.8 +/- 2.3 vs. 18.6 +/- 2.2 (P < 0.05) (step III). During insulin infusion lactate release (P < 0.05) [8.9 +/- 1.8 vs. 2.9 +/- 0.9 mumol.min-1.kg-1 (step I), 24.6 +/- 3.1 vs. 12.5 +/- 2.6 (step III)] and glycogen storage (P < 0.1) calculated by indirect calorimetry [6.7 +/- 2.3 vs. 5.0 +/- 1.7 mg.min-1.kg-1 (step I), 16.8 +/- 2.1 vs. 14.1 +/- 1.8 (step III)] were always higher in T than in UT legs. Release of glycerol, free fatty acids, and tyrosine and clearance of insulin were not influenced by training. Insulin-mediated glucose uptake was not increased after detraining or a single bout of exercise. In conclusion, training increases sensitivity and responsiveness of insulin-mediated glucose uptake in human muscle by local mechanisms. Glycolysis and glycogen storage are equally enhanced. The training effect represents a genuine adaptation to repeated exercise but is short lived. Insulin clearance in muscle is not influenced by training.

Effects on the immune system of 6-min "all-out" ergometer rowing were investigated over 2 days (2 x 3 bouts) in eight male oarsmen with a maximal oxygen uptake of 5.5 +/- 0.1 l/min (mean +/- SE). Blood samples were obtained before, during, and 2 h after each bout and on the day after the last bout. Compared with levels at rest, the first bout of exercise increased the concentration of leukocytes (2-fold); neutrophilic granulocytes (2-fold); lymphocytes (2-fold); monocytes (2-fold); the blood mononuclear cell (BMNC) subsets CD3+ (2-fold), CD4+ (2-fold), CD8+ (3-fold), CD16+ (8-fold), CD19+ (2-fold), and CD14+ (2-fold); the NK cell activity (2-fold); and plasma interleukin-6 (3-fold) (P < 0.05). During the last bout even higher levels were noted for leukocytes (3-fold); neutrophilic granulocytes (3-fold); lymphocytes (4-fold); the BMNC subsets CD4+ (3-fold), CD8+ (5-fold), CD16+ (13-fold), CD19+ (5-fold), and CD14+ (3-fold); and for the NK cell activity (4-fold) (P < 0.05). During the recovery periods all values were at or above the level at rest, and elevated concentrations of leukocytes (38%), neutrophilic granulocytes (48%), and lymphocytes (46%) reflected in the BMNC subsets and increased NK cell activity (119%) were also noted on the day after the last bout (P < 0.05). The results show that maximal exercise with large muscle groups provokes higher immune responses during repetitive bouts.