Prevention of ischemic-hypoxic brain injury and death in rabbits with fructose-1,6-diphosphate.

Abstract

Fructose-1,6-diphosphate has been shown to improve neurologic recovery following resuscitation from cardiac arrest and to restore brain electrical activity during hypoglycemic coma in rabbits. In view of these findings, we determined whether fructose-1,6-diphosphate protects the brain during ischemia-hypoxia. We subjected 16 rabbits to hypotension, hypoxemia, and bilateral common carotid artery occlusion. Five minutes after the onset of isoelectric electroencephalograms, seven randomly selected rabbits received 10% fructose-1,6-diphosphate (350 mg/kg bolus followed by 10 mg/kg/min infusion for 90 minutes) and the remaining nine rabbits (controls) received an equal volume of 1.5% NaCl (3.5 ml/kg bolus followed by 0.1 ml/kg/min infusion for 90 minutes). After isoelectricity lasting 7.86 +/- 0.8 minutes (mean +/- SEM) in the treated group and 6.44 +/- 0.38 minutes in the control group, the rabbits were reinfused with autologous shed blood and reoxygenated and the carotid artery occluders were removed. Treated rabbits recovered electrical activity more rapidly than the controls (p less than 0.005), and all seven treated rabbits survived. Only two controls (22%) survived (p less than 0.001), and they were severely disabled. Histology showed extensive cortical necrosis and focal necrosis in the hippocampi and cerebellum of brains from the two surviving controls. Brains from two treated rabbits exhibited minimal neuronal loss limited to the neocortex, and the brains from the remaining five treated rabbits were normal. This study suggests that fructose-1,6-diphosphate protects the brain from ischemic-hypoxic insults.