Impact of acute mild and severe poikilocapnic hypoxia on dynamic cerebral autoregulation and its directional sensitivity in young healthy volunteers

Dynamic cerebral autoregulation (dCA) stabilizes cerebral blood flow (CBF) during rapid mean arterial pressure (MAP) changes and exhibits directional sensitivity (i.e. attenuated CBF responses to transient MAP increases compared with MAP decreases). Hypoxia may impair this regulatory capacity and promote CBF instability. Whether the severity of poikilocapnic hypoxia differentially influences dCA and its hysteresis-like pattern remains unclear. This study examines the impact of acute mild [fraction of inspired oxygen (FiO 2 =0.16)], and severe (FiO 2 =0.10) hypoxia, compared to normoxia (FiO 2 =0.21), on dCA and its directional sensitivity. Twenty participants completed 6-min oscillatory lower body negative pressure (OLBNP) trials at 0.05 and 0.10 Hz in three distinct sessions, where MAP and middle cerebral artery mean blood velocity (MCAv) were continuously recorded. dCA and its hysteresis-like pattern were quantified using transfer function analysis (TFA) and directional sensitivity analysis [with time-adjusted ratios of relative MCAv to MAP changes calculated for each transition during MAP increases (RelMCAv T /RelMAP T INCREASE ) and decreases (RelMCAv T /RelMAP T DECREASE )], respectively. Severe hypoxia increased MAP (p=0.042) and MCAv (p=0.013) power and decreased TFA phase (p=0.026) at 0.05 Hz OLBNP compared to normoxia. Mild hypoxia did not influence dCA. Regardless of hypoxia severity, RelMCAvT/RelMAPT INCREASE was lower than RelMCAv T /RelMAP T DECREASE at 0.05 Hz (p=0.007) and 0.10 Hz (p=0.008) OLBNP. These results suggest that acute severe, but not mild hypoxia, impairs dCA at 0.05 Hz OLBNP, reflecting reduced buffering capacity of the cerebral circulation. Nonetheless, the hysteresis-like pattern of dCA observed in normoxia remains unaffected by hypoxia severity, suggesting distinct regulatory mechanisms for dCA and its directional sensitivity under hypoxic stress.