Changes in brain monoamine metabolism in rats with acute ischemic hepatic failure under artificial cardiopulmonary management.

Abstract

A study was conducted to investigate changes in monoamine metabolism in the brain of rats with acute ischemic hepatic failure (AHF) induced by two-stage hepatic devascularization. Strict artificial cardiopulmonary management was used to exclude possible confounding effects of hypotension, hypothermia and hypoxemia that often appear in AHF. Rats were put in an incubator at 34 degrees C before the ligation of the hepatic artery (second stage operation), tracheotomized and ventilated artificially throughout the remaining experimental periods. No significant difference was observed in physiological parameters, including body temperature, pulse rate and systolic arterial blood pressure or PaO2 between AHF and sham operated rats. Brain levels of norepinephrine (NE) and its metabolite 3-methoxy-4-hydroxyphenylglycol (MHPG), dopamine (DA) and its metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanilic acid (HVA), and serotonin (5-hydroxytryptamine, 5HT) and its metabolite 5-hydroxyindoleacetic acid (5HIAA) were determined by HPLC-voltametry. AHF rats showed significantly higher MHPG, DOPAC, 5HIAA and lower NE levels in the brain compared to controls. In addition, a significant negative correlation between NE and tyrosine (Tyr), a significant positive correlation between MHPG and Tyr or phenylalanine (Phe), and a significant positive correlation between DOPAC and Tyr or Phe were observed. In conclusion, the changes in monoamine metabolism in the brain of AHF rats are clearly induced specifically by hepatic failure itself, possibly through an altered metabolism of amino acids.