Abstract 102: Pharmacological Selective Inhibition Of Astrocyte Metabolism Improves Neurological Recovery After Cardiac Arrest In Rabbits

Introduction: Astrocytes promote cerebral inflammation during neuronal focal ischemic injury and lactate consumption by neurons. However, the physiopathological role of astrocytes remains to be established during cardiac arrest. Hypothesis: We hypothesized that inhibition of astrocytes metabolism by the citric acid cycle inhibitor fluorocitrate (FC) could improve the neurological recovery after a cardiac arrest. Methods: Anesthetized male New-Zealand rabbits randomly received an intrathecal injection of saline (Control) or FC (10 nmol/kg, “FC”) just before 10 min of ventricular fibrillation. In a first set of experiment (n=6 per group), we determined after resuscitation the cerebral consumptions of lactate and glucose by measuring their arteriojugular differences and the cerebral extracellular concentrations of several metabolites using a microdialysis probe during 4 h after cardiac arrest. In a second set of experiments (n=7 per group), neurological dysfunction was evaluated 24 h after cardiac arrest. Neuronal death and astrogliosis were quantified histologically. Results: In the first set of experiment, cerebral lactate consumption was significantly decreased in FC vs Control after cardiac arrest (6.4±2.3 and 14.5±4.7mmol/L/min, respectively). Extracellular concentration of lactate, pyruvate, glucose, glycerol or glutamate were similarin the 2 groups. In the second set of experiment, neurological outcome was significantly improved in FC vs Control at 24 h after cardiac arrest (19±7 vs 55±9% of neurological dysfunction score, respectively). Conclusions: Specific inhibition of citric acid cycle of astrocytes by FC is neuroprotective after cardiac arrest in rabbits.