Lactate and Pyruvate Changes in the Cerebral Gray and White Matter during Posthypoxic Seizures in Newborn Pigs

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Abstract

ABSTRACT

Cerebral lactate rises after chemically induced seizures, but it is not known if this occurs with posthypoxic seizures. We examined changes in lactate and pyruvate in gray and white matter in the newborn pig brain after a hypoxic insult known to produce seizures and permanent brain damage. Fourteen halothane-anesthetized piglets aged 24-49 h, were instrumented with a two-channel scalp EEG and microdialysis probes positioned in white and gray matter. Forty-five minutes of hypoxia were induced by reducing the fraction of inspired O2 to the maximum concentration at which EEG amplitude was <7 µV. Postinsult EEG was classified as electroconvulsive activity (ECA) (n = 4) or burst suppression (n = 2), persistently low amplitude (n = 2), or intermittent spikes on normal background activity (n = 6). Six hours after the insult the brains were perfusion fixed for histologic probe localization. Plasma lactate and brain lactate had different time courses with brain having a persistently elevated lactate/pyruvate (L/P) ratio. The highest L/P ratios in gray and white matter were in the two pigs with persistently low amplitude EEG. There was no association between onset of electroconvulsive activity and an increase in lactate or L/P ratio. Posthypoxic energy metabolism is disturbed in both gray and white matter probably because of mitochondrial dysfunction. Seizure activity does not increase cerebral lactate or L/P ratio above the already raised levels found in posthypoxic encephalopathy. These findings cast further doubt on the hypothesis that such seizures are, in themselves, damaging.

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