Effect of end-tidal CO2 clamping on cerebrovascular function, oxygenation, and performance during 15-km time trial cycling in severe normobaric hypoxia: the role of cerebral O2 delivery

Abstract

During heavy exercise, hyperventilation-induced hypocapnia leads to cerebral vasoconstriction, resulting in a reduction in cerebral blood flow (CBF). A reduction in CBF would impair cerebral O2 delivery and potentially account for reduced exercise performance in hypoxia. We tested the hypothesis that end-tidal Pco2 (PETCO2) clamping in hypoxic exercise would prevent the hypocapnia-induced reduction in CBF during heavy exercise, thus improving exercise performance. We measured PETCO2, middle cerebral artery velocity (MCAv; index of CBF), prefrontal cerebral cortex oxygenation (cerebral O2Hb; index of cerebral oxygenation), cerebral O2 delivery (DO2), and leg muscle oxygenation (muscle O2Hb) in 10 healthy men (age 27 ± 7 years; VO2max 63.3 ± 6.6 mL/kg/min; mean ± SD) during simulated 15-km time trial cycling (TT) in normoxia and hypoxia (FIO2 = 0.10) with and without CO2 clamping. During exercise, hypoxia elevated MCAv and lowered cerebral O2Hb, cerebral DO2, and muscle O2Hb (P < 0.001). CO2 clamping elevated PETCO2 and MCAv during exercise in both normoxic and hypoxic conditions (P < 0.001 and P = 0.024), but had no effect on either cerebral and muscle O2Hb (P = 0.118 and P = 0.124). Nevertheless, CO2 clamping elevated cerebral DO2 during TT in both normoxic and hypoxic conditions (P < 0.001). CO2 clamping restored cerebral DO2 to normoxic values during TT in hypoxia and tended to have a greater effect on TT performance in hypoxia compared to normoxia (P = 0.097). However, post hoc analysis revealed no effect of CO2 clamping on TT performance either in normoxia (P = 0.588) or in hypoxia (P = 0.108). Our findings confirm that the hyperventilation-induced hypocapnia and the subsequent drop in cerebral oxygenation are unlikely to be the cause of the reduced endurance exercise performance in hypoxia.

Keywords: CO2 clamping; exercise; hypoxia; ventilatory control.

Figure 1

Effect of hypoxia and CO₂ clamping on respiratory variables during 15-km time trial cycling. Left panels, group data in normoxia (mean ± SD); right panels, group data in hypoxia. •, normoxia control; ○, normoxia CO₂ clamp; ▪, hypoxia control; □, hypoxia CO₂ clamp.

Figure 2

Effect of hypoxia and CO₂ clamping on cerebral variables during 15-km time trial cycling. Cerebral O₂Hb and HHb are expressed at delta changes from normoxia (room air baseline). Left panels, group data in normoxia (mean ± SD); right panels, group data in hypoxia. •, normoxia control; ○, normoxia CO₂ clamp; ▪, hypoxia control; □, hypoxia CO₂ clamp.

Figure 3

Effect of hypoxia and CO₂ clamping on muscle oxygenation during 15-km time trial cycling. Muscle O₂Hb and HHb are expressed at delta changes from normoxia (room air baseline). Left panels, group data in normoxia (mean ± SD); right panels, group data in hypoxia. •, normoxia control; ○, normoxia CO₂ clamp; ▪, hypoxia control; □, hypoxia CO₂ clamp.