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Hypoxia increases the ventilatory response to exercise, which leads to hyperventilation-induced hypocapnia and subsequent reduction in cerebral blood flow (CBF). We studied the effects of adding CO 2  to a hypoxic inspired gas on CBF during heavy exercise in an altitude naïve population. We hypothesized that augmented inspired CO 2  and hypoxia would exert synergistic effects on increasing CBF during exercise, which would improve exercise capacity compared to hypocapnic hypoxia. We also examined the responsiveness of CO 2  and O 2  chemoreception on the regulation ventilation (    E) during incremental exercise. We measured middle cerebral artery velocity (MCAv; index of CBF),E, end-tidal PCO 2 , respiratory compensation threshold (RC) and ventilatory response to exercise (    E slope) in ten healthy men during incremental cycling to exhaustion in normoxia and hypoxia (FIO 2  = 0.10) with and without augmenting the fraction of inspired CO 2  (FICO 2 ). During exercise in normoxia, augmenting FICO 2  elevated MCAv throughout exercise and lowered both RC onset and    E slope below RC (P<0.05). In hypoxia, MCAv andE slope below RC during exercise were elevated, while the onset of RC occurred at lower exercise intensity (P<0.05). Augmenting FICO 2  in hypoxia increasedE at RC (P<0.05) but no difference was observed in RC onset, MCAv, orE slope below RC (P>0.05). TheE slope above RC was unchanged with either hypoxia or augmented FICO 2  (P>0.05). We found augmenting FICO 2  increased CBF during sub-maximal exercise in normoxia, but not in hypoxia, indicating that the ‘normal’ cerebrovascular response to hypercapnia is blunted during exercise in hypoxia, possibly due to an exhaustion of cerebral vasodilatory reserve. This finding may explain the lack of improvement of exercise capacity in hypoxia with augmented CO 2 . Our data further indicate that, during exercise below RC, chemoreception is responsive, while above RC the ventilatory response to CO 2  is blunted.

The Effect of Adding CO2 to Hypoxic Inspired Gas on Cerebral Blood Flow Velocity and Breathing during Incremental Exercise