Fructose-1,6-bisphosphate supports cerebral energy metabolism in pigs after ischemic brain injury caused by experimental particle embolization.
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.
Kaakinen
Timo
T
Department of Surgery, Oulu University Hospital, University of Oulu, Oulu, Finland. timo.kaakinen@oulu.fi
Heikkinen
Janne
J
Dahlbacka
Sebastian
S
Alaoja
Hanna
H
Laurila
Päivi
P
Kiviluoma
Kai
K
Salomäki
Timo
T
Romsi
Pekka
P
Tuominen
Hannu
H
Biancari
Fausto
F
Lepola
Pasi
P
Nuutinen
Matti
M
Juvonen
Tatu
T
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
D005635:Fructosediphosphates; D018696:Neuroprotective Agents; D019344:Lactic Acid; D019289:Pyruvic Acid; C029063:fructose-1,6-diphosphate