It has been hypothesized that γ-aminobutyric acid (GABA), the principle inhibitory neurotransmitter of the mammalian brain, contributes to the neural inhibition of hepatic encephalopathy. Eck fistulae were created in seven dogs and celiotomy alone performed in five dogs to determine plasma GABA levels, brain GABA binding, and synaptic membrane changes in dogs after creation of Eck fistulae. Eck fistula dogs lost 19 ± 9% body weight, lost hair, ate poorly, and developed atrophic livers with classic hepatic histological changes. Control dogs maintained body weight, normal behavior, and normal liver histology. Plasma GABA levels were elevated significantly in the Eck fistula dogs (312 ± 105.9 nM) both as compared to controls (154.4 ± 69.8) and to preoperative levels (161.6 ± 56.7, P < 0.05). Brain GABA binding for animals sacrificed at 6-9 weeks was not statistically different from sham-operated dogs sacrificed at 6 weeks (1.87 ± .54 pmole/mg protein vs 1.186 ± 24, P < 0.2). Synaptic membrane fluidity and cholesterol were likewise unchanged. Plasma GABA levels are increased significantly following complete portal diversion but do not correlate with the degree of encephalopathy. GABA binding to neural membranes are not significantly increased in Eck fistula dogs. These findings do not support a direct relationship between plasma GABA levels and neurologic impairment in Eck fistula dogs.
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