Evidence for central hypertyraminemia in hepatic encephalopathy.

Abstract

A B S T R A C T In mongrel dogs, the effect of end-to- side portacaval shunt on plasma, cerebrospinal fluid (CSF) and brain tyramine, tyrosine, dopamine, norepinephrine, and epinephrine were studied. It was found that the level of tyramine in plasma, CSF, and selected brain regions increased steadily after the construction of the shunts. These elevations became more pro- nounced when the dogs manifested symptoms of hepatic encephalopathy. In postshunted dogs with stage II and III hepatic encephalopathy, tyramine concentration in corpus striatum (1,312371), hypothalamus (400+67.0), and midbrain (66078.7 ng/g) was significantly (P < 0.05) higher than the level in dogs with stage 0 and I hepatic encephalopathy and sham-operated dogs serving as controls (corpus striatum, 831+140; hypothalamus, 167+40.0; and midbrain, 132+37.4 ng/g). This was followed by a con- comitant depletion of dopamine and norepinephrine in these brain regions (postshunt: dopamine 10420.0, 3,697+977, and 10514.1; norepinephrine 52171.6, 81.613.7, and 21831.7 ng/g; vs. sham group: dopamine 53283.1, 8,210+1,126, and 19235.0; norepi- nephrine 1,338+425, 12421.3, and 44989.7 ng/g) ofen- cephalopathic dogs with portacaval shunt. Further- more, tyramine, tyrosine, dopamine, and norepi- nephrine levels in plasma and CSF increased markedly as clinical features in the dogs' behavior characteristic of hepatic encephalopathy occurred, including hyper- salivation, ataxia, flapping tremor, somnolence, and coma.