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J Thorac Cardiovasc Surg 2003;125:686-698
© 2003 The American Association for Thoracic Surgery

Cardiopulmonary Support and Physiology

Fructose-1,6-bisphosphate for improved outcome after hypothermic circulatory arrest in pigs

From the Departments of Surgery,^a Anesthesiology,^b Forensic Medicine,^c and Pediatrics,^d Oulu University Hospital, University of Oulu, Oulu, Finland.

Supported by grants from the Oulu University Hospital, Oulu University, the Finnish Foundation for Cardiovascular Research, and the Sigrid Juselius Foundation.

Received for publication March 21, 2002. Revisions requested May 24, 2002; revisions received May 30, 2002. Accepted for publication June 6, 2002. Address for reprints: Tatu Juvonen, MD, PhD, Department of Surgery, Oulu University Hospital, PO Box 21, 900251 Oulu, Finland (E-mail: tatu.juvonen{at}oulu.fi).

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.

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				T. Kaakinen, A. Naukkarinen, H. Tuominen, P. Romsi, M. Nuutinen, F. Biancari, and T. Juvonen Neuronal ultrastructure is preserved by fructose-1,6-bisphosphate after hypothermic circulatory arrest in pigs J. Thorac. Cardiovasc. Surg., November 1, 2005; 130(5): 1475 - 1476. [Full Text] [PDF]