title: Cerebral microcirculation is impaired during sepsis: an experimental study.
abstract: BACKGROUND
  Pathophysiology of brain dysfunction due to sepsis remains poorly understood. Cerebral microcirculatory alterations may play a role; however, experimental data are scarce. This study sought to investigate whether the cerebral microcirculation is altered in a clinically relevant animal model of septic shock.
  
  
  METHODS
  Fifteen anesthetized, invasively monitored, and mechanically ventilated female sheep were allocated to a sham procedure (n = 5) or sepsis (n = 10), in which peritonitis was induced by intra-abdominal injection of autologous faeces. Animals were observed until spontaneous death or for a maximum of 20 hours. In addition to global hemodynamic assessment, the microcirculation of the cerebral cortex was evaluated using Sidestream Dark-Field (SDF) videomicroscopy at baseline, 6 hours, 12 hours and at shock onset. At least five images of 20 seconds each from separate areas were recorded at each time point and stored under a random number to be analyzed, using a semi-quantitative method, by an investigator blinded to time and condition.
  
  
  RESULTS
  All septic animals developed a hyperdynamic state associated with organ dysfunction and, ultimately, septic shock. In the septic animals, there was a progressive decrease in cerebral total perfused vessel density (from 5.9 ± 0.9 at baseline to 4.8 ± 0.7 n/mm at shock onset, P = 0.009), functional capillary density (from 2.8 ± 0.4 to 2.1 ± 0.7 n/mm, P = 0.049), the proportion of small perfused vessels (from 95 ± 3 to 85 ± 8%, P = 0.02), and the total number of perfused capillaries (from 22.7 ± 2.7 to 17.5 ± 5.2 n/mm, P = 0.04). There were no significant changes in microcirculatory flow index over time. In sham animals, the cerebral microcirculation was unaltered during the study period.
  
  
  CONCLUSIONS
  In this model of peritonitis, the cerebral microcirculation was impaired during sepsis, with a significant reduction in perfused small vessels at the onset of septic shock. These alterations may play a role in the pathogenesis of septic encephalopathy.
authors.affiliation: Department of Intensive Care, Erasme Hospital, Université Libre de Bruxelles, Route de Lennik 808, 1070 Bruxelles, Belgium. ftaccone@ulb.ac.be
authors.forename: Fabio Silvio
authors.initials: FS
authors.lastname: Taccone
authors.forename: Fuhong
authors.initials: F
authors.lastname: Su
authors.forename: Charalampos
authors.initials: C
authors.lastname: Pierrakos
authors.forename: Xinrong
authors.initials: X
authors.lastname: He
authors.forename: Syril
authors.initials: S
authors.lastname: James
authors.forename: Olivier
authors.initials: O
authors.lastname: Dewitte
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Vincent
authors.forename: Daniel
authors.initials: D
authors.lastname: De Backer
mesh_terms: D000818:Animals; D001784:Blood Gas Analysis; D001794:Blood Pressure / Q000502:physiology; D001921:Brain / Q000098:blood supply / Q000503:physiopathology; D002540:Cerebral Cortex / Q000098:blood supply; D002560:Cerebrovascular Circulation / Q000502:physiology*; D004195:Disease Models, Animal; D005260:Female; D007773:Lactates / Q000097:blood; D008833:Microcirculation / Q000502:physiology*; D018715:Microscopy, Video; D018805:Sepsis / Q000503:physiopathology*; D012756:Sheep; D012772:Shock, Septic / Q000503:physiopathology
chemical_list: D007773:Lactates