Lactate is involved in the occurrence of neurological damages after experimental cardiac arrest in rabbits

Introduction Lactate can be used by neurons as a metabolic substrate after an ischemic injury. Though, its consequences on neuronal mortality are still unknown after cardiac arrest. Objective We investigated the neurological consequences of blood lactate after cardiac arrest by administration of exogenous lactate or pyruvate, its main metabolite. Then, we tested the effect of oxamate, which inhibits the reduction of lactate to pyruvate. Method Anesthetized rabbits were submitted to 10 min of ventricular fibrillation and resuscitated. In a first set of experiments, they randomly received saline (Control group, n = 7), lactate (Lac group, 10 mg/kg/min, n = 6) or pyruvate (Pyr group, 10 mg/kg/min, n = 7). In a second set of experiments, they randomly received saline (Control group, n = 7) or oxamate (Oxa group, 37.5 mg/kg/min, n = 6). Animals were followed during 48 h for neurological and survival evaluation. Neuronal death and astrogliosis were quantified by immunostaining (fluorojade C and GFAP, respectively). Results Lactate and pyruvate administration significantly exacerbated blood lactate levels 30 min after cardiac arrest as compared to Control group (15.8 ± 0.8 and 15.0 ± 0.8 vs. 13.1 ± 0.9 mmol/L in Lac, Pyr and Control groups, respectively). This led to a greater neuronal death and neurological dysfunction vs. Control (66 ± 12 and 100 ± 6 vs. 48 ± 8% of neuronal dysfunction after 48 h, in Lac, Pyr and Control groups respectively). Astrogliosis significantly increased after pyruvate infusion vs. other groups (68 ± 5 vs. 49 ± 4 and 54 ± 3 reactive astrocytes per field, in Pyr, Lac and Control groups respectively). In the second set of experiment, oxamate infusion was potently neuroprotective (13 ± 5 vs. 60 ± 10% of neuronal dysfunction after 48 h, in Oxa and Control groups, respectively). Conclusion Lactate and pyruvate administration enhances blood lactate levels and worsen the neurological death while inhibition of lactate dehydrogenase is neuroprotective.