Reductions in systemic and locomotor limb muscle blood flow and O 2 delivery limit aerobic capacity in humans. To examine whether O 2 delivery limits both aerobic power and capacity, we first measured systemic haemodynamics, O 2 transport and O 2 uptake (V O 2 ) during incremental and constant (372 ± 11 W; 85% of peak power; mean ± S.E.M.) cycling exercise to exhaustion (n = 8) and then measured systemic and leg haemodynamics andV O 2 during incremental cycling and knee-extensor exercise in male subjects (n = 10). During incremental cycling, cardiac output (Q) and systemic O 2 delivery increased linearly to 80% of peak power (r 2 = 0.998, P < 0.001) and then plateaued in parallel to a decline in stroke volume (SV) and an increase in central venous and mean arterial pressures (P < 0.05). In contrast, heart rate andV O 2 increased linearly until exhaustion (r 2 = 0.993; P < 0.001) accompanying a rise in systemic O 2 extraction to 84 ± 2%. In the exercising legs, blood flow and O 2 delivery levelled off at 73-88% of peak power, blunting legV O 2 per unit of work despite increasing O 2 extraction. When blood flow increased linearly during one-legged knee-extensor exercise,V O 2 per unit of work was unaltered on fatigue. During constant cycling,Q, SV, systemic O 2 delivery andV O 2 reached maximal values within ∼5 min, but dropped before exhaustion (P < 0.05) despite increasing or stable central venous and mean arterial pressures. In both types of maximal cycling, the impaired systemic O 2 delivery was due to the decline or plateau inQ because arterial O 2 content continued to increase. These results indicate that an inability of the circulatory system to sustain a linear increase in O 2 delivery to the locomotor muscles restrains aerobic power. The similar impairment in SV and O 2 delivery during incremental and constant load cycling provides evidence for a central limitation to aerobic power and capacity in humans.

During maximal exercise in humans, fatigue is preceded by reductions in systemic and skeletal muscle blood flow, O 2 delivery and uptake. Here, we examined whether the uptake of O 2 and substrates by the human brain is compromised and whether the fall in stroke volume of the heart underlying the decline in systemic O 2 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 O 2 and glucose did not change, whereas middle cerebral artery mean flow velocity (MCA V mean ) and cardiac output increased by ∼22 and ∼115%, respectively. Thereafter, brain extraction of O 2 , glucose and lactate increased by ∼45, ∼55 and ∼95%, respectively, while frontal cortex tissue oxygenation, MCA V mean and cardiac output declined ∼40, ∼15 and ∼10%, respectively. At exhaustion in both trials, systemicV O 2 declined in parallel with a similar fall in stroke volume and central venous pressure; yet the brain uptake of O 2 , glucose and lactate increased. In conclusion, the reduction in stroke volume, which underlies the fall in systemic O 2 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 O 2 and substrates.

We investigated whether dynamic cerebral autoregulation is affected by exhaustive exercise using transfer-function gain and phase shift between oscillations in mean arterial pressure (MAP) and middle cerebral artery (MCA) mean blood flow velocity (V(mean)). Seven subjects were instrumented with a brachial artery catheter for measurement of MAP and determination of arterial Pco(2) (Pa(CO(2))) while jugular venous oxygen saturation (Sv(O(2))) was determined to assess changes in whole brain blood flow. After a 10-min resting period, the subjects performed dynamic leg-cycle ergometry at 168 +/- 5 W (mean +/- SE) that was continued to exhaustion with a group average time of 26.8 +/- 5.8 min. Despite no significant change in MAP during exercise, MCA V(mean) decreased from 70.2 +/- 3.6 to 57.4 +/- 5.4 cm/s, Sv(O(2)) decreased from 68 +/- 1 to 58 +/- 2% at exhaustion, and both correlated to Pa(CO(2)) (5.5 +/- 0.2 to 3.9 +/- 0.2 kPa; r = 0.47; P = 0.04 and r = 0.74; P < 0.001, respectively). An effect on brain metabolism was indicated by a decrease in the cerebral metabolic ratio of O(2) to [glucose + one-half lactate] from 5.6 to 3.8 (P < 0.05). At the same time, the normalized low-frequency gain between MAP and MCA V(mean) was increased (P < 0.05), whereas the phase shift tended to decrease. These findings suggest that dynamic cerebral autoregulation was impaired by exhaustive exercise despite a hyperventilation-induced reduction in Pa(CO(2)).

The Frank-Starling 'law of the heart' is implicated in certain types of orthostatic intolerance in humans. Environmental conditions have the capacity to modulate orthostatic tolerance, where heat stress decreases and cooling increases orthostatic tolerance. The objective of this project was to test the hypothesis that heat stress augments and cooling attenuates orthostatic-induced decreases in stroke volume (SV) via altering the operating position on a Frank-Starling curve. Pulmonary artery catheters were placed in 11 subjects for measures of pulmonary capillary wedge pressure (PCWP) and SV (thermodilution derived cardiac output/heart rate). Subjects experienced lower-body negative-pressure (LBNP) of 0, 15 and 30 mmHg during normothermia, skin-surface cooling (decrease in mean skin temperature of 4.3 ± 0.4• C (mean ± s.e.m.) via perfusing 16• C water through a tubed-lined suit), and whole-body heating (increase in blood temperature of 1.0 ± 0.1• C via perfusing 46 • C water through the suit). SV was 123 ± 8, 121 ± 10, 131 ± 7 ml prior to LBNP, during normothermia, skin-surface cooling, and whole-body heating, respectfully (P = 0.20). LBNP of 30 mmHg induced greater decreases in SV during heating (−48.7 ± 6.7 ml) compared to normothermia (−33.2 ± 7.4 ml) and to cooling (−10.3 ± 2.9 ml; all P < 0.05). Relating PCWP to SV indicated that cooling values were located on the flatter portion of a Frank-Starling curve because of attenuated decreases in SV per decrease in PCWP. In contrast, heating values were located on the steeper portion of a Frank-Starling curve because of augmented decreases in SV per decrease in PCWP. These data suggest that a Frank-Starling mechanism may contribute to improvements in orthostatic tolerance during cold stress and orthostatic intolerance during heat stress.