DIFFERENTIATION BETWEEN THE EFFECTS OF UNPROCESSED PORTAL BLOOD AND REDUCED LIVER-FUNCTION ON BRAIN INDOLE AMINE METABOLISM IN THE PORTACAVAL SHUNTED RAT

Changes in brain 5-HT turnover which have been associated with portal- systemic encephalopathy (PSE) in man were studied in rats with experim ental PSE for intervals up to 15 weeks following the surgical construc tion of end-to-side portacaval shunts (PCS). These were compared to ch anges measured in portacaval transposed rats (PCT) which, show little hepatic dysfunction or cerebral abnormalities but, in common with the PCS rat, sustain total portal-systemic diversion. Thus any differences between these two groups were indicative of hepatic dysfunction and n ot the systemic diversion of portal blood. After 15 weeks, sustained i ncreases were measured in brainstem and cerebral concentrations of the catabolite of 5-hydroxytryptamine (5-HT), 5-hydroxyindole acetic acid (5-HIAA), from 0.25+/-0.01 to 0.68+/-0.01** mu g g(-1) brain and fro m 0.18+/-0.01 to 0.31+/-0.03** mu g g(-1) brain respectively in PCS r ats and were statistically greater to those measured in the brainstem and cerebrum of PCT and control rats. Sustained increases in cerebral concentrations alone of 5-hydroxytryptophan (5-HTP), the precursor of 5-HT, from 0.17+/-0.01 to 0.23+/-0.02 mu g g(-1) brain were measured i n PCS rats and were significantly** greater than in PCT control rats after 15 weeks. Some early increases in 5-HTP were measured in PCS abo ve control rats but these were not significant after 15 weeks. No sust ained significant differences between the 3 groups were measured in 5- HT after 15 weeks. These data confirm previous evidence chat the eleva tions in 5-HTP and 5-HIAA concentrations observed in experimental chro nic liver failure and PSE are due to liver dysfunction and not portal- systemic diversion and may contribute additional information regarding the role of derangements in central 5-HT turnover as one of the cause s of PSE. **p<0.001, Newman-Keuls ANOVAR followed by Student's unpair ed t-test for individual comparisons, (data shown are mean +/- SEM).