The effect of liver ischaemia on brain monoamine synthesis in the rat

Subtotal or total liver ischaemia was induced in the rat by dividing the hepatic artery (Expt. I) or by total dearterialisation of the liver (Expt. II) 2 days after porta-caval shunt (PCS). The animals received i.v. a 10% glucose infusion for 5 h after the last operation and were killed by decapitation. At the end of the experiment all animals with liver ischaemia were in Grade III coma. In different regions of the CNS 5-hydroxytryptophan (5-HTP), 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA), were analysed by HPLC-technique with electrochemical detection, while dihydroxyphenylalanine (DOPA), dopamine (DA) and norepinephrine (NE) were analysed with a radio enzymatic method after blocking the decarboxylation of 5-HTP to 5-HT and DOPA to DA by inhibition of the aromatic amino acid decarboxylase enzyme with m-hydroxybenzylhydrazine (NSD 1015) in order to estimate the synthesis rate of 5-hydroxyindoles and catecholamines. In Expt. I concentrations of 5-HTP in animals with PCS were increased as compared to sham operation. In animals with liver ischaemia, 5-HTP concentrations were increased as compared to sham operation but similar to those in animals with PCS alone. These results suggest that ligation of the hepatic artery for 5 h in PCS animals does not further accelerate the rate of brain indole synthesis. In Expt. II, the 5-HTP concentrations were increased in PCS animals as compared to sham operation. Animals with total liver dearterialisation exhibited decreased 5-HTP levels as compared to PCS, suggesting a decreased brain indole synthesis after severe liver ischaemia. In Expt. II, CNS concentrations of DOPA following PCS were unaltered as compared with sham-operated animals. In animals with total liver dearterialisation, DOPA levels were increased, suggesting an augmented catecholamine synthesis. The NE levels were lower than in PCS and in sham-operated animals.