title: Fructose-1,6-bisphosphate for improved outcome after hypothermic circulatory arrest in pigs.
abstract: OBJECTIVE
  Fructose-1,6-bisphosphate is a high-energy intermediate in the anaerobic metabolism. It enhances glycolysis, preserves cellular adenosine triphosphate, and prevents the increase of intracellular calcium during ischemia. The potential neuroprotective effect of fructose-1,6-bisphosphate during hypothermic circulatory arrest was evaluated in a surviving porcine model.
  
  
  METHODS
  Twenty-four pigs were randomly assigned to receive two intravenous infusions of either fructose-1,6-bisphosphate (500 mg/kg) or saline solution. The first infusion was given immediately before a 75-minute period of hypothermic circulatory arrest and the second was given immediately after hypothermic circulatory arrest.
  
  
  RESULTS
  The 7-day survivals were 83.3% in the fructose-1,6-bisphosphate group and 41.7% in the control group (P =.09). The treated animals had significantly better postoperative behavioral scores. The administration of fructose-1,6-bisphosphate was associated with higher venous phosphate and sodium levels, lower venous ionized calcium levels, higher blood osmolarity, and a better fluid balance. Intracranial pressure and venous creatine kinase isoenzyme MB were significantly lower in the fructose-1,6-bisphosphate group during rewarming (P =.01 and P =.001, respectively). Among the treated animals, brain glucose, pyruvate and lactate levels tended to be higher, brain glycerol levels tended to be lower, and the histopathologic score of the brain was significantly lower (P =.04).
  
  
  CONCLUSIONS
  Intravenous administration of fructose-1,6-bisphosphate at 500 mg/kg before and after hypothermic circulatory arrest in a surviving porcine model was associated with better survival, behavioral outcome, and histopathologic score. The observed lower blood creatine kinase isoenzyme MB and brain glycerol levels and the higher brain glucose, pyruvate, and lactate levels in the fructose-1,6-bisphosphate group suggest that this drug has supportive effects on myocardial and brain metabolisms.
authors.affiliation: Department of Surgery, Oulu University Hospital, University of Oulu, Finland.
authors.forename: Pekka
authors.initials: P
authors.lastname: Romsi
authors.forename: Timo
authors.initials: T
authors.lastname: Kaakinen
authors.forename: Kai
authors.initials: K
authors.lastname: Kiviluoma
authors.forename: Vilho
authors.initials: V
authors.lastname: Vainionpää
authors.forename: Jorma
authors.initials: J
authors.lastname: Hirvonen
authors.forename: Matti
authors.initials: M
authors.lastname: Pokela
authors.forename: Pasi
authors.initials: P
authors.lastname: Ohtonen
authors.forename: Fausto
authors.initials: F
authors.lastname: Biancari
authors.forename: Matti
authors.initials: M
authors.lastname: Nuutinen
authors.forename: Tatu
authors.initials: T
authors.lastname: Juvonen
mesh_terms: D000818:Animals; D001923:Brain Chemistry; D002545:Brain Ischemia / Q000209:etiology* / Q000378:metabolism / Q000401:mortality / Q000517:prevention & control*; D002118:Calcium / Q000097:blood; D003402:Creatine Kinase / Q000097:blood; D052279:Creatine Kinase, MB Form; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D005260:Female; D005635:Fructosediphosphates / Q000494:pharmacology / Q000627:therapeutic use*; D005947:Glucose / Q000032:analysis; D005990:Glycerol / Q000032:analysis; D006324:Heart Arrest, Induced / Q000009:adverse effects*; D007036:Hypothermia, Induced / Q000009:adverse effects*; D007262:Infusions, Intravenous; D007527:Isoenzymes / Q000097:blood; D019344:Lactic Acid / Q000032:analysis; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D010758:Phosphorus / Q000097:blood; D019289:Pyruvic Acid / Q000032:analysis; D011897:Random Allocation; D012964:Sodium / Q000097:blood; D016019:Survival Analysis; D013552:Swine; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D005635:Fructosediphosphates; D007527:Isoenzymes; D018696:Neuroprotective Agents; D010758:Phosphorus; D019344:Lactic Acid; D019289:Pyruvic Acid; D012964:Sodium; D003402:Creatine Kinase; D052279:Creatine Kinase, MB Form; D005947:Glucose; C029063:fructose-1,6-diphosphate; D005990:Glycerol; D002118:Calcium