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

Abstract

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.

Keywords: cerebral blood flow; chronic fatigue syndrome; cognition; n-back testing; orthostatic challenge.

Copyright © 2014 the American Physiological Society.

Figures

Fig. 1.

Comparison of Baseline-Supine and 60° head-up tilt (HUT) cardiorespiratory dynamics in control and chronic fatigue syndrome (CFS) subjects showing mean blood pressure, heart rate in beats/minute (bpm), respiratory rate, and end-tidal carbon dioxide (ETCO2). Data are shown as means ± SE. *Significantly different comparing Baseline-Supine to HUT (P < 0.05); ‡significantly different comparing control to CFS (P < 0.05).

Fig. 2.

Comparison of Baseline-Supine and 60° HUT cerebral blood flow velocity in control and CFS subjects. Data are shown as means ± SE. *Significantly different comparing Baseline-Supine to HUT (P < 0.05); ‡significantly different comparing control to CFS (P < 0.05).

Fig. 3.

Comparison of Baseline-Supine to Baseline-Supine with phenylephrine and 60° HUT with phenylephrine (HUT with Tx) cardiorespiratory dynamics in control and CFS subjects showing mean blood pressure, heart rate, respiratory rate, and ETCO2. Data are shown as means ± SE. *Significantly different comparing Baseline-Supine to HUT (P < 0.05); ‡significantly different comparing control to CFS (P < 0.05).

Fig. 4.

Comparison of Baseline-Supine to Baseline-Supine with phenylephrine and 60° HUT with phenylephrine (HUT with Tx) cerebral blood flow velocity in control and CFS subjects. Data are shown as means ± SE. *Significantly different comparing Baseline-Supine to phenylephrine (P < 0.05).

Fig. 5.

Neurocognitive function evaluated by n-back testing comparing normalized reaction time measured in control subjects (top), supine and during HUT, to that measured in CFS subjects (bottom), supine and during HUT. *Significantly different, comparing responses measured supine with those during HUT (P < 0.05).

Fig. 6.

Neurocognitive function evaluated by n-back testing measured in CFS subjects during HUT, with and without phenylephrine. *Significantly different, comparing responses with and without phenylephrine (P < 0.05).