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

Abstract

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.

Concentrations of 3,4‐Dihydroxyphenylalanine and Catecholamines and Metabolites in Brain in an Anhepatic Model of Hepatic Encephalopathy

“…The decrease in NE concentration in the brain following hepatectomy is consistent with findings in other animal models of acute hepatic encephalopathy . The reproducibility of this finding in such diverse models of hepatic encephalopathy as complete hepatectomy [both two- (Tyce and Owen, 1978) and three-stage (Bugge et al, 1986)] and partial or totally devascularized liver (Dodsworth et al, 1974;Bugge et al ., 1987), as well as a chemical model using thioacetamide (Yurdaydin et al ., 1990), conveys the potential significance of alterations in noradrenergic neurotransmitters in hepatic coma .…”