Phenylephrine alteration of cerebral blood flow during orthostasis: effect on n-back performance in chronic fatigue syndrome

Chronic fatigue syndrome (CFS) with orthostatic intolerance is characterized by neurocognitive deficits and impaired working memory, concentration, and information processing. In CFS, upright tilting [head-up tilt (HUT)] caused decreased cerebral blood flow velocity (CBFv) related to hyperventilation/hypocapnia and impaired cerebral autoregulation; increasing orthostatic stress resulted in decreased neurocognition. We loaded the baroreflex with phenylephrine to prevent hyperventilation and performed n-back neurocognition testing in 11 control subjects and 15 CFS patients. HUT caused a significant increase in heart rate (109.4 +/- 3.9 vs. 77.2 +/- 1.6 beats/min, P < 0.05) and respiratory rate (20.9 +/- 1.7 vs. 14.2 +/- 1.2 breaths/min, P < 0.05) and decrease in end-tidal CO2 (ETCO2; 42.8 +/- 1.2 vs. 33.9 +/- 1.1 Torr, P < 0.05) in CFS vs. control. HUT caused CBFv to decrease 8.7% in control subjects but fell 22.5% in CFS. In CFS, phenylephrine prevented the HUT-induced hyperventilation/hypocapnia and the significant drop in CBFv with HUT (-8.1% vs. -22.5% untreated). There was no difference in control subject n-back normalized response time (nRT) comparing supine to HUT (106.1 +/- 6.9 vs. 97.6 +/- 7.1 ms at n = 4), and no difference comparing control to CFS while supine (97.1 +/- 7.1 vs 96.5 +/- 3.9 ms at n = 4). However, HUT of CFS subjects caused a significant increase in nRT (148.0 +/- 9.3 vs. 96.4 +/- 6.0 ms at n = 4) compared with supine. Phenylephrine significantly reduced the HUT-induced increase in nRT in CFS to levels similar to supine (114.6 +/- 7.1 vs. 114.6 +/- 9.3 ms at n = 4). Compared with control subjects, CFS subjects are more sensitive both to orthostatic challenge and to baroreflex/chemoreflex-mediated interventions. Increasing blood pressure with phenylephrine can alter CBFv. In CFS subjects, mitigation of the HUT-induced CBFv decrease with phenylephrine has a beneficial effect on n-back outcome.