Fructose-1,6-bisphosphate for improved outcome after hypothermic circulatory arrest in pigs.
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.
Romsi
Pekka
P
Department of Surgery, Oulu University Hospital, University of Oulu, Finland.
Kaakinen
Timo
T
Kiviluoma
Kai
K
Vainionpää
Vilho
V
Hirvonen
Jorma
J
Pokela
Matti
M
Ohtonen
Pasi
P
Biancari
Fausto
F
Nuutinen
Matti
M
Juvonen
Tatu
T
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
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