Therapeutic acute intermittent hypoxia does not alter whole-brain cerebrovascular function in healthy individuals

Abstract

Acute intermittent hypoxia (AIH) therapy is a promising intervention known to elicit beneficial neuroplasticity. It has been suggested that AIH may also modulate cerebrovascular function, yet the cerebrovascular effects of specific therapeutic intermittent hypoxia protocols remain poorly characterized. Understanding whether AIH results in favorable or adverse cerebrovascular changes is critical in establishing the safety of AIH treatments in populations with elevated cerebrovascular risk. This study investigated cerebral blood flow, cerebrovascular reactivity to hypoxia, and blood pressure effects in a sham-controlled crossover trial (NCT05164705). Healthy young adults (n=18) completed three-week arms of AIH (12 sessions, 15 cycles of 60 seconds hypoxia alternated with 60 seconds normoxia) and sham (6 sessions, normoxia) treatments; phase-contrast and arterial spin labeling magnetic resonance imaging were used to quantify whole-brain and regional cerebral blood flow and hypoxic cerebrovascular reactivity. Blood pressure was measured acutely (before and after each intervention session) and longitudinally (before and after 3 weeks of treatment). AIH treatment did not significantly alter whole-brain resting cerebral blood flow or cerebrovascular reactivity to hypoxia. Blood pressure was unaffected by the treatment acutely or longitudinally. Voxel-wise analysis identified modest regional perfusion increases in the frontal pole, postcentral gyri, and precentral gyri with AIH relative to sham. Significant variability between subjects and between sessions in the hypoxic burden delivered with this AIH protocol was also identified. Overall, this three-week therapeutic AIH protocol produced minimal sustained hemodynamic changes in healthy young adults. The insights from this trial lay a foundation for safely expanding access to this promising rehabilitative intervention in clinical populations.