Hepatic encephalopathy in cirrhotic and portacaval shunted dogs: lack of changes in brain GABA uptake, brain GABA levels, brain glutamic acid decarboxylase activity and brain postsynaptic GABA receptors.

Abstract

It has been suggested, from studies of a rabbit model of fulminant hepatic failure, that hepatic encephalopathy might be related to an increase in brain gamma-aminobutyric acid uptake through a more permeable bloodbrain barrier, leading to an overactivity of brain gamma-aminobutyric acid-mediated inhibitory neurotransmission. Five groups of dogs were studied: normal dogs, dogs with secondary biliary cirrhosis without and with hepatic encephalopathy and portacaval shunted dogs without and with hepatic encephalopathy. Brain gamma-aminobutyric acid and sucrose uptake was investigated using the multiple indicator dilution curve technique in unanesthetized dogs. Tracer doses of 99mTc-labeled albumin (extracellular reference substance), 3H-labeled gamma-aminobutyric acid and 14C-labeled sucrose prepared in autologous dog plasma were injected in one carotid artery, and dorsal sagittal sinus dilution curves were obtained. Uptake was calculated by comparing the areas under the 99mTc-labeled albumin and the [3H]gamma-aminobutyric acid (or [14C]sucrose) curves from appearance to peak height. After killing, brain gamma-aminobutyric acid levels were measured in the frontal cortex by high-performance liquid chromatography and glutamic acid decarboxylase activities using a radioenzymatic assay. Brain gamma-aminobutyric acid postsynaptic receptors were assessed using [3H]muscimol binding studies. There were no significant changes in cirrhotic and shunted dogs with or without hepatic encephalopathy with regard to brain gamma-aminobutyric acid and sucrose uptake, brain gamma-aminobutyric acid levels and glutamic acid decarboxylase activities. [3H]Muscimol binding studies did not show any changes in the number nor in the affinity of postsynaptic gamma-aminobutyric acid receptors.(ABSTRACT TRUNCATED AT 250 WORDS)