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 shamoperated animals.
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Bengtsson F, Gage FH, Jeppsson B, Nobin A, Rosengren E (1985) Brain monoamine metabolism and behaviour in portacaval shunted rats. Exp Neurol 90:21–35
Bengtsson F, Nobin A, Falck B, Gage FH, Jeppsson B (1986) Portacaval shunt in the rat: Selective alterations in behaviour and brain serotonin. Pharmacol Biochem Behaviour 24:1611–1616
Borg J, Warter JM, Schlienger JL, Imler M, Marescaux C, Mack G (1982) Neurotransmitter modifications in human cerebrospinal fluid and serum during hepatic encephalopathy. J Neurol Sci 57:343–356
Bugge M, Bengtsson F, Nobin A, Jeppsson B, Herlin P (1986) The metabolism of monoamines in the brain after total hepatectomy in the rat. Exp Neurol 94:11–20
Carlsson A, Davis JN, Kehr W, Lindqvist M, Atack CV (1972) Simultaneous measurement of tyrosine and tryptophan hydroxylase activities in brain in vivo using an inhibitor of the aromatic amino acid decarboxylase. Naunyn-Schmiedebergs Arch Pharmacol 275:153–168
Cuilleret C, Pomier-Layrargues G, Pons F, Cardilhac J, Michel H (1980) Changes in brain catecholamine levels in human cirrhotic hepatic encephalopathy. Gut 21:565–569
Cummings MG, James JH, Soeters PB, Keane JM, Forster J, Fischer JE (1976) Regional brain study of indoleamine metabolism in the rat in acute hepatic failure. J Neurochem 27:741–746
Curzon G, Kantamaneni BD, Winch J, Rojas-Bueno A, Murray-Lyon IM, Williams R (1973) Plasma and brain tryptophan changes in experimental acute hepatic failure. J Neurochem 21:137–145
Dodsworth JM, James JH, Cummings MC, Fischer JE (1974) Depletion of brain norepinephrine in acute hepatic coma. Surgery 75:811–820
Fernström JD, Wurtman RJ (1972) Brain serotonin content: Physiological regulation by plasma neutral amino acids. Science 178:414–416
Fischer JE, Yoshimura N, Aguirra A et al. (1974) Plasma amino acids in patients with hepatic encephalopathy. Effects of amino acids infusions. Am J Surg 127:40–47
Fischer JE, Baldessarini RJ (1976) Pathogenesis and therapy of hepatic coma. In: Popper H, Schaffner F (eds) Progress in liver disease, Grune & Stratton, New York, pp 363–397
Franco MMD, Bismuth H (1977) Necrose ischemique hepatique chez le rat. Influence de la necrose sur l'evolution de l'insuffisance hepatique aigue. Bordeaux Medical 10:1823–1826
Herlin P, James JH, Gimmon Z, Fischer JE (1982) Combined or individual administration of branched-chain amino acids following total hepatectomy in the rat: Effects on amino acids and indoleamines in brain. JPEN 6:383–387
Holmin T, Siesjö BK (1974) The effect of porta-caval anastomosis upon the energy state and upon acid-base parameters of the rat brain. J Neurochem 22:403–412
Hutson DG, Ono J, Dombro RS, Levi JU, Linvingstone A, Zeppa R (1979) A longitudinal study of tryptophan involvement in hepatic coma. Am J Surg 137:235–239
Jellinger K, Riederer P, Kleinberger G, Wuketich S, Kothbauer P (1978) Brain monoamines in human hepatic encephalopathy. Acta Neuropathol (Berl) 43:63–68
Jonung T, Ramzy A, Herlin P, James JH, Edwards L, Fischer JE (1985) Indole amines and amino acids in various brain regions after infusion of branched chain amino acids into hepatectomized rats. Eur Surg Res 17:83–90
Livingstone AS, Potvin M, Goresky CA, Finlayson MH, Hinchey EJ (1977) Changes in the blood brain barrier in hepatic coma after hepatectomy in the rat. Gastroenterology 73:697–704
Mans AM, Biebuyck JF, Saunders SJ, Kirsch RE, Hawkins RA (1979) Tryptophan transport across the blood-brain barrier during acute hepatic failure. J Neurochem 33:409–418
Miller RG (1981) Simultaneous statistical interference. In: Brillinger D, Fienberg S, Gani J, Hartigan J, Kiefer J, Krickeberg K (eds) Springer series in statistics, 2nd edn. Springer, Heidelberg Berlin New York, pp 81–90, 234–237
Nobin A, Karp W, Lunderquist A, Rosengren E, Sanden G, Sundler F (1982) Localization of carcinoids and pheochromocytomas with vein catherization and amine determination. Brain Res Bull 9:781–797
Record CO, Buxton B, Chase RA, Curzon G, Murray-Lyon IM, Williams R (1976) Plasma and brain amino acids in fulminant hepatic failure and their relationship to hepatic encephalopathy. Eur J Clin Invest 6:387–394
Rosen HM, Yoshimura N, Hodgman JM, Fischer JE (1977) Plasma amino acid patterns in hepatic encephalopathy of differing etiology. Gastroenterology 72:483–487
Rössle M, Luft M, Herz R, Klein B, Lehmann M, Gerok W (1984) Amino acid, ammonia and neurotransmitter concentrations in hepatic encephalopathy: Serial analysis in plasma and cerebrospinal fluid during treatment with an adapted amino acid solution. Klin Wochenschr 62:867–875
Schmidt RH, Ingvar M, Lindvall O, Stenevi U, Björklund A (1982) Functional activity of substantia nigra grafts reinnervating the striatum: Neurotransmitter metabolism and (14C)2-D-glucose autoradiography. J Neurochem 38(2):737–748
Tyce GM, Owen CA Jr (1978) Dopamine and norepinephrine in the brains of hepatectomized rats. Life Sci 22(9):781–785
Supported by the Medical Faculty, University of Lund, Sweden and the Swedish Medical Research Council (grant no. 12X-712 and 14X-56)
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Bugge, M., Bengtsson, F., Nobin, A. et al. The effect of liver ischaemia on brain monoamine synthesis in the rat. Res. Exp. Med. 187, 119–130 (1987). https://doi.org/10.1007/BF01851973
- Liver ischaemia
- Decarboxylase inhibition
- Porta caval shunt (PCS)