THE BARBITURATE THIOPENTAL REDUCES ATP LEVELS DURING ANOXIA BUT IMPROVES ELECTROPHYSIOLOGICAL RECOVERY AND IONIC HOMEOSTASIS IN THE RAT HIPPOCAMPAL SLICE

The barbiturate anesthetic thiopental enhances recovery of the evoked population spike recorded from rat hippocampal slices after short periods of anoxia. Thiopental reduces changes in sodium, potassium and calcium but enhances the fall in ATP levels during anoxia. The postsynaptic population spike recorded from the CA1 pyramidal cell region of the slices treated with thiopental (600-mu-m) recovered to 67% of the preanoxic amplitude after 3.5 min of anoxia. There was less recovery (24%) when a lower concentration of thiopental (250-mu-m) was used. Untreated slices recovered to only 10% of their preanoxic amplitude after 3.5 min of anoxia. Other studies have demonstrated that maintaining ATP levels during anoxia may be an important mechanism of protection. In contrast to those studies, thiopental was protective although it enhanced the fall of ATP levels after 3.5 min of anoxia in the CA1 region and after 3.5 and 5 min in the dentate region. Thus enhanced recovery of the population spike with thiopental is not due to its preservation of ATP levels. This result allows a clear separation of improved ATP levels during anoxia from other mechanisms of protection. We therefore looked for other mechanisms of protection. Sodium and potassium levels were measured after 10 min of anoxia. In untreated tissue, sodium levels in the slice rose and potassium levels fell significantly. In thiopental-treated tissue, changes in sodium and potassium caused by anoxia and by veratridine under normoxic conditions were significantly reduced. During anoxia calcium-45 uptake increases; thiopental significantly reduces this uptake. We have found that high concentrations of thiopental protect against short periods of anoxia. Thiopental does not protect by attenuating the fall in ATP during anoxia. We conclude that thiopental blocks sodium, potassium and calcium changes during anoxia and we postulate that this may be a mechanism by which it improves recovery after anoxia.