title: Sepsis is associated with altered cerebral microcirculation and tissue hypoxia in experimental peritonitis.
abstract: OBJECTIVE
  Alterations in cerebral microvascular blood flow may develop during sepsis, but the consequences of these abnormalities on tissue oxygenation and metabolism are not well defined. We studied the evolution of microvascular blood flow, brain oxygen tension (PbO2), and metabolism in a clinically relevant animal model of septic shock.
  
  
  METHODS
  Prospective randomized animal study.
  
  
  METHODS
  University hospital research laboratory.
  
  
  METHODS
  Fifteen invasively monitored and mechanically ventilated female sheep.
  
  
  METHODS
  The sheep were randomized to fecal peritonitis (n = 10) or a sham procedure (n = 5), and craniectomies were performed to enable evaluation of cerebral microvascular blood flow, PbO2, and metabolism. The microvascular network of the left frontal cortex was evaluated (at baseline, 6, 12, and 18 hr) using sidestream dark-field videomicroscopy. Using an off-line semiquantitative method, functional capillary density and the proportion of small perfused vessels were calculated. PbO2 was measured hourly by a parenchymal Clark electrode, and cerebral metabolism was assessed by the lactate/pyruvate ratio using brain microdialysis; both these systems were placed in the right frontal cortex.
  
  
  RESULTS
  In septic animals, cerebral functional capillary density (from 3.1 ± 0.5 to 1.9 ± 0.4 n/mm, p < 0.001) and proportion of small perfused vessels (from 98% ± 2% to 84% ± 7%, p = 0.004) decreased over the 18-hour study period. Concomitantly, PbO2 decreased (61 ± 5 to 41 ± 7 mm Hg, p < 0.001) and lactate/pyruvate ratio increased (23 ± 5 to 36 ± 19, p < 0.001). At 18 hours, when shock was present, animals with a mean arterial pressure less than 65 mm Hg (n = 6) had similar functional capillary density, proportion of small perfused vessels, and PbO2 values but significantly higher lactate/pyruvate ratio (46 ± 18 vs 20 ± 4, p = 0.009) compared with animals with an mean arterial pressure of 65-70 mm Hg (n = 4).
  
  
  CONCLUSIONS
  Impaired cerebral microcirculation during sepsis is associated with progressive impairment in PbO2 and brain metabolism. Development of severe hypotension was responsible for a further increase in anaerobic metabolism. These alterations may play an important role in the pathogenesis of brain dysfunction during sepsis.
authors.affiliation: 1Department of Intensive Care, Erasme Hospital, Université Libre de Bruxelles, Bruxelles, Belgium. 2Department of Anesthesia and Intensive Care, ZOL St-Jan, Genk, Belgium. 3Department of Neurosurgery, Erasme Hospital, Université Libre de Bruxelles, Bruxelles, Belgium.
authors.forename: Fabio Silvio
authors.initials: FS
authors.lastname: Taccone
authors.forename: Fuhong
authors.initials: F
authors.lastname: Su
authors.forename: Cathy
authors.initials: C
authors.lastname: De Deyne
authors.forename: Ali
authors.initials: A
authors.lastname: Abdellhai
authors.forename: Charalampos
authors.initials: C
authors.lastname: Pierrakos
authors.forename: Xinrong
authors.initials: X
authors.lastname: He
authors.forename: Katia
authors.initials: K
authors.lastname: Donadello
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; D001921:Brain / Q000378:metabolism; D002560:Cerebrovascular Circulation; D005260:Female; D000860:Hypoxia / Q000150:complications* / Q000503:physiopathology; D008833:Microcirculation; D010100:Oxygen / Q000378:metabolism; D010538:Peritonitis / Q000150:complications* / Q000503:physiopathology; D011446:Prospective Studies; D018805:Sepsis / Q000150:complications* / Q000209:etiology* / Q000503:physiopathology; D012756:Sheep
chemical_list: D010100:Oxygen