title: 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.
authors.affiliation: Department of Pediatrics, New York Medical College, Valhalla, New York; and Department of Physiology, New York Medical College, Valhalla, New York marvin_medow@nymc.edu.
authors.forename: Marvin S
authors.initials: MS
authors.lastname: Medow
authors.affiliation: Department of Pediatrics, New York Medical College, Valhalla, New York; and.
authors.forename: Shilpa
authors.initials: S
authors.lastname: Sood
authors.affiliation: Department of Pediatrics, New York Medical College, Valhalla, New York; and.
authors.forename: Zachary
authors.initials: Z
authors.lastname: Messer
authors.affiliation: Department of Pediatrics, New York Medical College, Valhalla, New York; and.
authors.forename: Seli
authors.initials: S
authors.lastname: Dzogbeta
authors.affiliation: Department of Pediatrics, New York Medical College, Valhalla, New York; and.
authors.forename: Courtney
authors.initials: C
authors.lastname: Terilli
authors.affiliation: Department of Pediatrics, New York Medical College, Valhalla, New York; and Department of Physiology, New York Medical College, Valhalla, New York.
authors.forename: Julian M
authors.initials: JM
authors.lastname: Stewart
mesh_terms: D000293:Adolescent; D000328:Adult; D001288:Attention / Q000187:drug effects; D017704:Baroreflex / Q000187:drug effects; D001783:Blood Flow Velocity; D001794:Blood Pressure / Q000187:drug effects; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D003071:Cognition / Q000187:drug effects*; D003072:Cognition Disorders / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology / Q000523:psychology; D015673:Fatigue Syndrome, Chronic / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology / Q000523:psychology; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D008568:Memory / Q000187:drug effects; D009483:Neuropsychological Tests; D054971:Orthostatic Intolerance / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology / Q000523:psychology; D056888:Patient Positioning; D010656:Phenylephrine / Q000008:administration & dosage*; D011187:Posture; D056152:Respiratory Rate / Q000187:drug effects; D018667:Tilt-Table Test; D016896:Treatment Outcome; D014662:Vasoconstrictor Agents / Q000008:administration & dosage*; D055815:Young Adult
chemical_list: D014662:Vasoconstrictor Agents; D010656:Phenylephrine
keywords: cerebral blood flow; chronic fatigue syndrome; cognition; n-back testing; orthostatic challenge