Can we improve exercise performance by increasing oxygen delivery to the brain?
Since previous studies have suggested that a lowering in oxygen delivery to the brain may eventually limit motor drive especially in hypoxic conditions, it would be cool to manipulate cerebral oxygen delivery to investigate if that variable influence exercise performance.
However, as stated by Subudhi et al. in the introduction of their last manuscript:
A specific method to alter cerebral oxygenation while holding all other physiological variables constant is needed to definitely test the hypothesis, but may be unrealistic to achieve in human subjects with available technology.
These authors theorized that inhaled CO2, that is a potent cerebral vasodilator, may be used to investigate the effects of increased brain oxygen delivery during exhaustive exercise. In this study, amateur cyclists aged between 18 and 45 years performed incremental exercise to exhaustion with and without clamped end-tidal CO2 (PetCO2) to supraphysiologic level (50 mmHg) with normal oxygen level (normoxia; barometric pressure around 630 mmHg) and low oxygen level (hypoxia; barometric pressure around 425 mmHg). The order of the tests (control and clamp) and conditions (normoxia and hypoxia) were randomly assigned and counterbalanced.
Changes in PetCO2, cerebral blood flow (measured by Transcranial Doppler; CBFv) and brain oxygenation (measured by near-infrared spectroscopy; TSI) are presented in the figure below (Control: dashed lines; Clamp: solid lines):
Exercise in normoxia
Clamping PetCO2 at 50 mmHg during incremental exercise in normoxia was associated with higher ventilation, end-tidal O2 (PetO2), cerebral blood flow and brain oxygenation at rest, during submaximal exercise and at exhaustion (without affecting muscle oxygenation).
However, maximal power output, peak oxygen consumption and maximal exercise heart rate were all reduced in comparison with the control exercise protocol (exercise in normoxia without clamping PetCO2). Hypercapnia was accompanied by both reduced blood pH and lactate concentrations.
Exercise in hypoxia
Clamping PetCO2 at 50 mmHg during incremental exercise in hypoxia was associated with higher ventilation, PetO2, cerebral blood flow and brain oxygenation at rest, during submaximal exercise and at exhaustion (without affecting muscle oxygenation at rest and at maximal exercise).
However, maximal power output and peak oxygen consumption were reduced in comparison with the control exercise protocol (exercise in hypoxia without clamping PetCO2). Hypercapnia was accompanied by both reduced blood pH and lactate concentrations.
To control for respiratory acidosis and the more important ventilatory drived induced in exercise conditions with CO2 clamping, the authors asked some subjects to perform an additional hypoxic trial with CO2 clamped at a lower level (40 mmHg; *PetCO2 was clamped only near exhaustion). In this exercise condition, ventilation, PetO2 and arterial pulse oxymetry were similar and cerebral blood flow velocity and oxygenation tended to be higher compared to the control trial (without CO2 clamping; see ‘Follow up’ in the figure above)
These results suggest that cerebral blood flow is most likely not the primary factor that limits incremental exercise performance in healthy amateur cyclists (and as suggested by the authors, at least when accompanied by respiratory acidosis).
Why exercise performance is reduced with this method?
Among the suggested factors that could explain that (surprising) reduced performance notwithstanding increased blood flow to the brain, the authors suggested pH-mediated impairment of performance, the finite structure of the subjects’ respiratory system and the diversion of blood flow away from exercising muscles (because of increased oxygen demand within respiratory muscles and cerebral vasodilatation induced by hypercapnia).
Where to go from here?
Future refinements to the method are needed to control for changes in acid-base balance to determine if small improvements in performance were potentially masked by deleterious effects of reduced pH.
It is definitely difficult to control for everything when studying healthy humans !
Subudhi AW, Olin JT, Dimmen AC, Polaner DM, Kayser B, Roach RC. Does cerebral oxygen delivery limit incremental exercise performance? J Appl Physiol Sep 15. Epub ahead of print doi:10.1152/japplphysiol.00569.201