Phenylephrine alters phase synchronization between cerebral blood velocity and blood pressure in ME/CFS with orthostatic intolerance.

Observed Findings

• During 60° head-up tilt, ME/CFS patients showed exaggerated hyperventilation (respiratory rate 20.9±1.7 breaths/min vs 14.2±1.2 in controls) and greater reductions in end-tidal CO₂ (33.9±1.1 Torr vs 42.8±1.2 in controls).
• Cerebral blood velocity decreased more sharply in ME/CFS (-22.5%) compared to controls (-8.7%) during tilt.
• Phase synchronization index increased during tilt in ME/CFS (indicating loss of cerebral autoregulation), but only phenylephrine significantly reversed this increase.
• N-back test accuracy during upright tilt was severely impaired in untreated ME/CFS (38.5±5.5% correct) but improved dramatically with phenylephrine (65.6±5.7%), approaching control performance (56.9±7.5%).
• Neither supplemental CO₂ nor acetazolamide improved cognitive performance or cerebral autoregulation despite reducing hyperventilation.

Inferred Conclusions

• Phenylephrine restores cerebral autoregulation in ME/CFS during orthostatic challenge, possibly through improved neurovascular coupling and maintenance of cerebral blood flow.
• The cognitive impairment in orthostatic ME/CFS is mechanistically linked to loss of cerebral autoregulation and reduced cerebral blood velocity, and these parameters can be acutely reversed pharmacologically.
• Phenylephrine's mechanism differs from CO₂ and acetazolamide, suggesting it works through direct hemodynamic stabilization rather than via ventilatory or acid-base modulation alone.

Remaining Questions