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

J Appl Physiol (1985). 2014 Nov 15;117(10):1157-64. doi: 10.1152/japplphysiol.00527.2014. Epub 2014 Oct 2.

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.

Publication types

  • Comparative Study
  • Controlled Clinical Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Attention / drug effects
  • Baroreflex / drug effects
  • Blood Flow Velocity
  • Blood Pressure / drug effects
  • Cerebrovascular Circulation / drug effects*
  • Cognition / drug effects*
  • Cognition Disorders / diagnosis
  • Cognition Disorders / drug therapy*
  • Cognition Disorders / physiopathology
  • Cognition Disorders / psychology
  • Fatigue Syndrome, Chronic / diagnosis
  • Fatigue Syndrome, Chronic / drug therapy*
  • Fatigue Syndrome, Chronic / physiopathology
  • Fatigue Syndrome, Chronic / psychology
  • Female
  • Heart Rate / drug effects
  • Humans
  • Male
  • Memory / drug effects
  • Neuropsychological Tests*
  • Orthostatic Intolerance / diagnosis
  • Orthostatic Intolerance / drug therapy*
  • Orthostatic Intolerance / physiopathology
  • Orthostatic Intolerance / psychology
  • Patient Positioning
  • Phenylephrine / administration & dosage*
  • Posture
  • Respiratory Rate / drug effects
  • Tilt-Table Test
  • Treatment Outcome
  • Vasoconstrictor Agents / administration & dosage*
  • Young Adult

Substances

  • Vasoconstrictor Agents
  • Phenylephrine