title: Gut microcirculatory and mitochondrial effects of hyperdynamic endotoxaemic shock and norepinephrine treatment.
abstract: BACKGROUND
  Microcirculatory and mitochondrial dysfunction are important factors in the development of septic shock. In this study, we investigated the effects of fluid resuscitated endotoxaemic shock and norepinephrine treatment on intestinal microcirculation and mitochondrial function in sheep.
  
  
  METHODS
  Eight anaesthetized sheep received an i.v. infusion of endotoxin. After 24 h, mean arterial pressure (MAP) was restored to baseline levels with a norepinephrine infusion. Five sheep served as sham experiments. Central and regional haemodynamics were monitored, and ileal microcirculation was evaluated with laser Doppler and sidestream dark-field videomicroscopy techniques. Gut mucosal acidosis was assessed by air tonometry, and ileal wall biopsies were analysed for mitochondrial activity.
  
  
  RESULTS
  After 24 h of endotoxaemia, the animals had developed hyperdynamic shock with systemic and mucosal acidosis. Although superior mesenteric artery (SMA) flow was higher than the baseline values, ileal microcirculatory perfusion and mitochondrial complex I activity decreased. After norepinephrine was started, SMA flow, ileal microcirculation, and mucosal acidosis remained unchanged. Although no statistically significant difference could be demonstrated, norepinephrine increased mitochondrial complex I activity in five of the six animals from which ileal biopsies were taken.
  
  
  CONCLUSIONS
  Although fluid resuscitated endotoxaemic shock increased regional blood flow, microcirculatory and mitochondrial alterations were still present. Restoring MAP with norepinephrine did not affect ileal microcirculation or mucosal acidosis, indicating that perfusion pressure manipulation is of limited importance to the intestinal microcirculation in established endotoxaemic shock.
authors.affiliation: Department of Anaesthesiology and Intensive Care, Karolinska University Hospital Huddinge, Sweden. andreas.andersson@karolinska.se
authors.forename: A
authors.initials: A
authors.lastname: Andersson
authors.forename: M
authors.initials: M
authors.lastname: Rundgren
authors.forename: S
authors.initials: S
authors.lastname: Kalman
authors.forename: O
authors.initials: O
authors.lastname: Rooyackers
authors.forename: O
authors.initials: O
authors.lastname: Brattstrom
authors.forename: A
authors.initials: A
authors.lastname: Oldner
authors.forename: S
authors.initials: S
authors.lastname: Eriksson
authors.forename: R
authors.initials: R
authors.lastname: Frithiof
mesh_terms: D000818:Animals; D002245:Carbon Dioxide / Q000097:blood; D004195:Disease Models, Animal; D019446:Endotoxemia / Q000188:drug therapy / Q000503:physiopathology*; D005260:Female; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D007082:Ileum / Q000098:blood supply*; D007413:Intestinal Mucosa / Q000098:blood supply; D017078:Laser-Doppler Flowmetry / Q000379:methods; D008833:Microcirculation / Q000187:drug effects / Q000502:physiology; D028361:Mitochondrial Diseases / Q000188:drug therapy / Q000209:etiology; D009638:Norepinephrine / Q000627:therapeutic use*; D010100:Oxygen / Q000097:blood; D010313:Partial Pressure; D012756:Sheep; D012772:Shock, Septic / Q000188:drug therapy / Q000503:physiopathology*; D014662:Vasoconstrictor Agents / Q000627:therapeutic use*
chemical_list: D014662:Vasoconstrictor Agents; D002245:Carbon Dioxide; D010100:Oxygen; D009638:Norepinephrine