Two-week normobaric intermittent-hypoxic exposures stabilize cerebral perfusion during hypocapnia and hypercapnia

The effect of moderately extended, intermittent-hypoxia (IH) on cerebral perfusion during changes in CO₂was unknown. Thus, we assessed the changes in cerebral vascular conductance (CVC) and cerebral tissue oxygenation (ScO₂) during experimental hypocapnia and hypercapnia following 14-day normobaric exposures to IH (10% O₂). CVC was estimated from the ratio of mean middle cerebral arterial blood flow velocity (transcranial Doppler sonography) to mean arterial pressure (tonometry), and ScO₂in the prefrontal cortex was monitored by near-infrared spectroscopy. Changes in CVC and ScO₂during changes in partial pressure of end-tidal CO₂(P_ETCO₂, mass spectrometry) induced by 30-s paced-hyperventilation (hypocapnia) and during 6-min CO₂rebreathing (hypercapnia) were compared before and after 14-day IH exposures in eight young nonsmokers. Repetitive IH exposures reduced the ratio of %ΔCVC/ΔP_ETCO₂during hypocapnia (1.00 ± 0.13 vs 1.94 ± 0.35 vs %/mmHg, P = 0.026) and the slope of ΔCVC/ΔP_ETCO₂during hypercapnia (1.79 ± 0.37 vs 2.97 ± 0.64 %/mmHg, P = 0.021), but had no significant effect on ΔScO₂/ΔP_ETCO₂. The ventilatory response to hypercapnia during CO₂rebreathing was significantly diminished following 14-day IH exposures (0.83 ± 0.07 vs 1.14 ± 0.09 L/min/mmHg, P = 0.009). We conclude that repetitive normobaric IH exposures significantly diminish variations of cerebral perfusion in response to hypercapnia and hypocapnia without compromising cerebral tissue oxygenation. This IH-induced blunting of cerebral vasoreactivity during CO₂variations helps buffer excessive oscillations of cerebral underperfusion and overperfusion while sustaining cerebral O₂homeostasis.