title: Fructose-1,6-bisphosphate supports cerebral energy metabolism in pigs after ischemic brain injury caused by experimental particle embolization.
abstract: BACKGROUND
  Fructose-1,6-bisphosphate (FDP) is a high-energy intermediate that enhances glycolysis, preserves cellular adenosine triphosphate stores, and prevents the increase of intracellular calcium in ischemic tissue. Since it has been shown to provide metabolic support to the brain during ischemia, we planned this study to evaluate whether FDP is neuroprotective in the setting of combining hypothermic circulatory arrest (HCA) and irreversible embolic brain ischemic injury.
  
  
  METHODS
  Twenty pigs were randomly assigned to receive 2 intravenous infusions of either FDP (500 mg/kg) or saline. The first infusion was given just before a 25-minute period of HCA and the second infusion immediately after HCA. Immediately before HCA, the descending aorta was clamped and 200 mg of albumin-coated polystyrene microspheres (250-750 mm in diameter) were injected into the isolated aortic arch in both study groups.
  
  
  RESULTS
  There were no significant differences between the study groups in terms of neurological outcome. Brain lactate/pyruvate ratio was significantly lower (P = .015) and brain pyruvate levels (P = .013) were significantly higher in the FDP group compared with controls. Brain lactate levels were significantly higher 8 hours after HCA (P = .049).
  
  
  CONCLUSIONS
  The administration of FDP before and immediately after HCA combined with embolic brain ischemic injury was associated with significantly lower brain lactate/pyruvate ratio and significantly higher levels of brain pyruvate, as well as lower lactate levels 8 hours after HCA. FDP seems to protect the brain by supporting energy metabolism. The neurological outcome was not improved, most likely resulting from the irreversible nature of the microsphere occlusion.
authors.affiliation: Department of Surgery, Oulu University Hospital, University of Oulu, Oulu, Finland. timo.kaakinen@oulu.fi
authors.forename: Timo
authors.initials: T
authors.lastname: Kaakinen
authors.forename: Janne
authors.initials: J
authors.lastname: Heikkinen
authors.forename: Sebastian
authors.initials: S
authors.lastname: Dahlbacka
authors.forename: Hanna
authors.initials: H
authors.lastname: Alaoja
authors.forename: Päivi
authors.initials: P
authors.lastname: Laurila
authors.forename: Kai
authors.initials: K
authors.lastname: Kiviluoma
authors.forename: Timo
authors.initials: T
authors.lastname: Salomäki
authors.forename: Pekka
authors.initials: P
authors.lastname: Romsi
authors.forename: Hannu
authors.initials: H
authors.lastname: Tuominen
authors.forename: Fausto
authors.initials: F
authors.lastname: Biancari
authors.forename: Pasi
authors.initials: P
authors.lastname: Lepola
authors.forename: Matti
authors.initials: M
authors.lastname: Nuutinen
authors.forename: Tatu
authors.initials: T
authors.lastname: Juvonen
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism*; D002545:Brain Ischemia / Q000209:etiology / Q000378:metabolism*; D050792:Circulatory Arrest, Deep Hypothermia Induced / Q000009:adverse effects*; D004195:Disease Models, Animal; D004734:Energy Metabolism / Q000187:drug effects*; D005635:Fructosediphosphates / Q000008:administration & dosage*; D020766:Intracranial Embolism / Q000209:etiology / Q000378:metabolism*; D019344:Lactic Acid / Q000378:metabolism; D018696:Neuroprotective Agents / Q000008:administration & dosage; D019289:Pyruvic Acid / Q000378:metabolism; D013552:Swine
chemical_list: D005635:Fructosediphosphates; D018696:Neuroprotective Agents; D019344:Lactic Acid; D019289:Pyruvic Acid; C029063:fructose-1,6-diphosphate