EFFECTS OF SIMULATED UPPER GASTROINTESTINAL HEMORRHAGE ON AMMONIA ANDRELATED AMINO-ACIDS IN BLOOD AND BRAIN OF CHRONIC PORTACAVAL-SHUNTED RATS

Gastrointestinal (GI) hemorrhage during compromised liver function is known to precipitate portal-systemic encephalopathy (PSE). Hypothetica lly, the induced hyperammonemia depletes cerebral glutamate pools. To investigate this hypothesis, rats were studied 14 days after portacava l shunt (PCS) or sham surgery (SHAM). Rats received 3 mt bovine erythr ocytes or saline at t= 0, 1, 2, and 3h via a previously placed gastros tomy catheter. At t= 0, 2, 4, 6 and 8h arterial blood and at t=8h cere bral cortex were sampled for determination of ammonia and amino acids. Control rats (NORM) were sampled without previous surgery. Repeated i ntragastric blood administration increased the already elevated arteri al ammonia levels in PCS rats further. This resulted in higher cerebra l cortex ammonia and glutamine levels after blood administration. Desp ite the accumulation of ammonia and glutamine, cerebral cortex glutama te concentrations remained unaltered. Yet, PCS rats became more enceph alopathic after blood gavages, suggesting that there is not a clear-cu t relation between cerebral cortex glutamate concentrations and degree of PSE. Interestingly, cerebral cortex concentrations of GABA, tyrosi ne and phenylalanine were markedly increased. Whether these observatio ns are pathogenetically related to PSE remains to be established. The present model of simulated GI hemorrhage in PCS rats seems to be a sui table, clinically valid model for future research regarding hepatic en cephalopathy.