Relationship between the autonomic nervous system and cerebral autoregulation during controlled breathing

Abstract Introduction Controlled breathing is a hemodynamic maneuver known to influence both baroreflex and chemoreflex sensitivity. This study investigated the impact of respiratory-driven oscillations on the relationship between cerebral autoregulation and autonomic nervous system (ANS) activity. Methods Sixty-one volunteers (median age: 23 years) underwent noninvasive measurements of arterial blood pressure (ABP), cerebral blood velocity (CBv), end-tidal CO 2 (EtCO 2 ), and respiratory rate during spontaneous breathing and during three 5-min sessions of controlled breathing at 6, 10, and 15 bpm. Cerebral autoregulation was assessed using transfer function analysis by calculating phase shift (PS) and gain between ABP and CBv in the very low frequency (VLF; 0.02–0.07 Hz) and breathing frequency (BF; 0.1, 0.17, 0.25 ± 0.02 Hz) ranges. ANS activity was assessed using baroreflex sensitivity (xBRS), heart rate variability (HRV) metrics in time and frequency domains, and entropy-based parameters. Cardiovascular coupling was assessed using the joint symbolic dynamics of beat-to-beat pulse interval and systolic blood pressure. Results Increasing respiratory rate led to decreased EtCO 2 ( p < 0.001), diminished cardiovascular coupling ( p < 0.01), and reduced systemic ABP control, as indicated by lower normalized low-frequency HRV and xBRS (both p < 0.001). A linear mixed-effects model, adjusted for EtCO 2 and respiratory rate, showed that PS at VLF and BF was modulated by ANS metrics, whereas gain was mainly affected by respiratory parameters, with a nonsignificant contribution from ANS. Conclusions Higher respiratory rates reduced cardiovascular coupling, diminished ANS activity, and modified its interaction with cerebral autoregulation. Respiratory parameters should be considered when assessing ANS–cerebral autoregulation relationship.