Effects of Simulated Upper Gastrointestinal Hemorrhage on Ammonia and Related Amino Acids in Blood and Brain of Chronic Portacaval-shunted Rats

Abstract

Gastrointestinal (GI) hemorrhage during compromised liver function is known to precipitate portal-systemic encephalopathy (PSE). Hypothetically, the induced hyperammonemia depletes cerebral glutamate pools. To investigate this hypothesis, rats were studied 14 days after portacaval shunt (PCS) or sham surgery (SHAM). Rats received 3 mL bovine erythrocytes or saline at t = 0, 1, 2, and 3h via a previously placed gastrostomy catheter. At t = 0, 2, 4, 6 and 8h arterial blood and at t = 8h cerebral cortex were sampled for determination of ammonia and amino acids. Control rats (NORM) were sampled without previous surgery. Repeated intragastric blood administration increased the already elevated arterial ammonia levels in PCS rats further. This resulted in higher cerebral cortex ammonia and glutamine levels after blood administration. Despite the accumulation of ammonia and glutamine, cerebral cortex glutamate concentrations remained unaltered. Yet, PCS rats became more encephalopathic after blood gavages, suggesting that there is not a clear-cut relation between cerebral cortex glutamate concentrations and degree of PSE. Interestingly, cerebral cortex concentrations of GABA, tyrosine and phenylalanine were markedly increased. Whether these observations are pathogenetically related to PSE remains to be established. The present model of simulated GI hemorrhage in PCS rats seems to be a suitable, clinically valid model for future research regarding hepatic encephalopathy.

Ornithine phenylacetate prevents disturbances of motor-evoked potentials induced by intestinal blood in rats with portacaval anastomosis

“…Pyramidal signs are typically present in severe HE [23]; motor tract dysfunction can be demonstrated by transcranial magnetic stimulation in advanced cirrhosis and has been shown to be reversible after liver transplantation [24]. The administration of blood to PCA rats induces changes in behavior and in motor function [25]. In the current study, we assessed motor function using MEP and showed a decrease of the amplitude and a delay on the conduction of MEP after GIB.…”

Systemic inflammatory response exacerbates the neuropsychological effects of induced hyperammonemia in cirrhosis

“…6 Simulating the metabolic effects of an UGIB by the oral administration of erythrocytes has been shown to induce hyperammonemia and behavioural disturbance in portacaval shunted rats. 7 In a recently published placebo-controlled study, we showed that simulating an UGIB by the oral administration of a specifically prepared amino acid (aa) solution identical to the aa profile of hemoglobin to patients with well-compensated cirrhosis, resulted in hyperammonemia but was not associated with significant deterioration in neuropsychological tests. However, the neuropsychological function in the group administered the placebo improved significantly suggesting that induced hyperammonemia produced a learning difficulty in the population studied.…”

A modified microsurgical model for end-to-side selective portacaval shunt in the rat: intraoperative microcirculatory investigations

“…Additionally, laboratory rats proved to be excellent models to study liver cirrhosis 11 , as well as hepatic encephalopathy [31][32][33] . In those experiments the liver atrophy and regeneration 34 , microvascular structural changes 35 , as well as remote effects were studied.…”