title: Cerebral metabolism during experimental endotoxin shock and after preconditioning with monophosphoryl lipid A.
abstract: OBJECTIVE
  Preconditioning with low doses of monophosphoryl lipid A (MPL) has been shown to induce endotoxin tolerance and to reduce the metabolic and hemodynamic consequences of endotoxin shock. However, no data are available about the effects of endotoxin preconditioning on cerebral metabolism during endotoxemia. The study was designed to determine the effects of endotoxin preconditioning with MPL on cerebral metabolism via microdialysis compared to muscle tissue metabolism during experimental endotoxemia.
  
  
  METHODS
  In a controlled animal study, continuous endotoxin infusion (1μg/kg b.w. per h) was administrated to 7 female mixed-breed pigs after pretreatment with MPL in incremental doses of endotoxin during days 5-2 before the experiments. In the control group, 7 animals received a saline pretreatment. In addition to hemodynamic monitoring and blood gas analyses, interstitial lactate, pyruvate, glucose and glycerol concentrations in muscle and cerebral tissue were measured using in vivo microdialysis.
  
  
  RESULTS
  There were no significant differences between the two groups with respect to hemodynamic parameters, while mixed venous oxygen saturation (SvO2), arterial blood pH and mean pulmonary arterial pressure (MPAP) were significantly higher in the preconditioned group. Cerebral perfusion pressure (CPP) and brain tissue oxygen pressure (ptiO2) values stayed stable throughout the experiment with no inter-group differences. While interstitial concentrations of lactate and glycerol as well as the lactate/pyruvate (LP) and the lactate/glucose (LG) ratio in muscle tissues were significantly increased in control animals compared to those who had been pretreated with MPL; the results of cerebral microdialysis showed no significant changes in interstitial lactate or glycerol levels in both groups. However, the lactate/glucose (LG) ratio in the control group showed a significantly higher increase than in the preconditioned group.
  
  
  CONCLUSIONS
  Preconditioning with low doses of MPL ameliorates the negative metabolic effects of endotoxin shock in muscle tissue. With regard to cerebral metabolism, the present study suggests that MLP preconditioning provides moderate advantages, at least in an experimental model of endotoxin shock.
authors.affiliation: Department of Neurosurgery, University of Lübeck, Lübeck, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Ditz
authors.affiliation: Department of Anesthesiology, Sankt Ansgar-Krankenhaus, Höxter, Germany.
authors.forename: Ludger
authors.initials: L
authors.lastname: Bahlmann
authors.affiliation: Department of Anesthesiology, Herz-Jesu-Krankenhaus Hiltrup GmbH, Münster, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Klaus
authors.affiliation: Department of Obstetrics and Gynecology, Klinikum Osnabrück, Osnabrück, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Keck
authors.affiliation: Department of Pediatrics, Klinikum Bremen-Mitte, Bremen, Germany.
authors.forename: Nils
authors.initials: N
authors.lastname: Onken
authors.affiliation: Department of Neurosurgery, University of Lübeck, Lübeck, Germany. Electronic address: jan.gliemroth@t-online.de.
authors.forename: Jan
authors.initials: J
authors.lastname: Gliemroth
mesh_terms: D000818:Animals; D054022:Cerebrum / Q000378:metabolism*; D004195:Disease Models, Animal; D019446:Endotoxemia / Q000517:prevention & control*; D004731:Endotoxins / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D008050:Lipid A / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D017551:Microdialysis; D012772:Shock, Septic / Q000517:prevention & control*; D013552:Swine
chemical_list: D004731:Endotoxins; D008050:Lipid A; C048436:monophosphoryl lipid A
keywords: Endotoxemia; Metabolism; Microdialysis; Sepsis; Vaccination