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The Copenhagen Muscle Research Centre, Department of Anaesthesia, Rigshospitalet, University of Copenhagen, Denmark
During maximal exercise in humans, fatigue is preceded by reductions in systemic and skeletal muscle blood flow, O2 delivery and uptake. Here, we examined whether the uptake of O2 and substrates by the human brain is compromised and whether the fall in stroke volume of the heart underlying the decline in systemic O2 delivery is related to declining venous return. We measured brain and central haemodynamics and oxygenation in healthy males (n= 13 in 2 studies) performing intense cycling exercise (360 ± 10 W; mean ±S.E.M.) to exhaustion starting with either high (H) or normal (control, C) body temperature. Time to exhaustion was shorter in H than in C (5.8 ± 0.2 versus 7.5 ± 0.4 min, P < 0.05), despite heart rate reaching similar maximal values. During the first 90 s of both trials, frontal cortex tissue oxygenation and the arterial–internal jugular venous differences (a-v diff) for O2 and glucose did not change, whereas middle cerebral artery mean flow velocity (MCA Vmean) and cardiac output increased by 
22 and 115%, respectively. Thereafter, brain extraction of O2, glucose and lactate increased by 45, 55 and 95%, respectively, while frontal cortex tissue oxygenation, MCA Vmean and cardiac output declined 40, 15 and 10%, respectively. At exhaustion in both trials, systemic 
declined in parallel with a similar fall in stroke volume and central venous pressure; yet the brain uptake of O2, glucose and lactate increased. In conclusion, the reduction in stroke volume, which underlies the fall in systemic O2 delivery and uptake before exhaustion, is partly related to reductions in venous return to the heart. Furthermore, fatigue during maximal exercise, with or without heat stress, in healthy humans is associated with an enhanced rather than impaired brain uptake of O2 and substrates.
(Received 2 January 2004;
accepted after revision 3 March 2004;
first published online 5 March 2004)
Corresponding author J. González-Alonso: The Copenhagen Muscle Research Centre, Section 7652, Blegdamsvej 9, DK-2100 Copenhagen Ø, Denmark. Email: jga{at}cmrc.dk
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