title: Endotoxemia reduces cerebral perfusion but enhances dynamic cerebrovascular autoregulation at reduced arterial carbon dioxide tension.
abstract: OBJECTIVE
  The administration of endotoxin to healthy humans reduces cerebral blood flow but its influence on dynamic cerebral autoregulation remains unknown. We considered that a reduction in arterial carbon dioxide tension would attenuate cerebral perfusion and improve dynamic cerebral autoregulation in healthy subjects exposed to endotoxemia.
  
  
  METHODS
  Prospective descriptive study.
  
  
  METHODS
  Hospital research laboratory.
  
  
  METHODS
  Ten healthy young subjects (age: 32 ± 8 yrs [mean ± SD]; weight: 84 ± 10 kg; weight: 184 ± 5 cm; body mass index: 25 ± 2 kg/m2) participated in the study.
  
  
  METHODS
  Systemic hemodynamics, middle cerebral artery mean flow velocity, and dynamic cerebral autoregulation evaluated by transfer function analysis in the very low (<0.07 Hz), low (0.07-0.15 Hz), and high (>0.15 Hz) frequency ranges were monitored in these volunteers before and after an endotoxin bolus (2 ng/kg; Escherichia coli).
  
  
  RESULTS
  Endotoxin increased body temperature of the subjects from 36.8 ± 0.4°C to 38.6 ± 0.5°C (p < .001) and plasma tumor necrosis factor-α from 5.6 (2.8-6.7) pg/mL to 392 (128-2258) pg/mL (p < .02). Endotoxemia had no influence on mean arterial pressure (95 [74-103] mm Hg vs. 92 [78-104] mm Hg; p = .75), but increased cardiac output (8.3 [6.1-9.5] L·min(-1) vs. 6.0 [4.5-8.2] L·min(-1); p = .02) through an elevation in heart rate (82 ± 9 beats·min(-1) vs. 63 ± 10 beats·min(-1); p < .001), whereas arterial carbon dioxide tension (37 ± 5 mm Hg vs. 41 ± 2 mm Hg; p < .05) and middle cerebral artery mean flow velocity (37 ± 9 cm·sec(-1) vs. 47 ± 10 cm·sec(-1); p < .01) were reduced. In regard to dynamic cerebral autoregulation, endotoxemia was associated with lower middle cerebral artery mean flow velocity variability (1.0 ± 1.0 [cm·sec(-1)] Hz vs. 2.8 ± 1.5 [cm·sec(-1)] Hz; p < .001), reduced gain (0.52 ± 0.11 cm·sec(-1) x mm Hg(-1) vs. 0.74 ± 0.17 cm·sec(-1) x mm Hg(-1); p < .05), normalized gain (0.22 ± 0.05 vs. 0.40 ± 0.17%·%; p < .05), and higher mean arterial pressure-to-middle cerebral artery mean flow velocity phase difference (p < .05) in the low frequency range (0.07-0.15 Hz).
  
  
  CONCLUSIONS
  These data support that the reduction in arterial carbon dioxide tension explains the improved dynamic cerebral autoregulation and the reduced cerebral perfusion encountered in healthy subjects during endotoxemia.
authors.affiliation: Department of Anesthesia, The Copenhagen Muscle Research Center, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Patrice
authors.initials: P
authors.lastname: Brassard
authors.forename: Yu-Sok
authors.initials: YS
authors.lastname: Kim
authors.forename: Johannes
authors.initials: J
authors.lastname: van Lieshout
authors.forename: Niels H
authors.initials: NH
authors.lastname: Secher
authors.forename: Jaya B
authors.initials: JB
authors.lastname: Rosenmeier
mesh_terms: D000328:Adult; D001783:Blood Flow Velocity; D002245:Carbon Dioxide / Q000097:blood*; D002560:Cerebrovascular Circulation / Q000502:physiology*; D019446:Endotoxemia / Q000503:physiopathology*; D006706:Homeostasis / Q000502:physiology*; D006801:Humans; D020768:Middle Cerebral Artery / Q000502:physiology*; D010313:Partial Pressure; D011446:Prospective Studies
chemical_list: D002245:Carbon Dioxide