47 HYPERAMMONEMIC SYNDROMES, INCLUDING ACUTE HEPATIC ENCEPHALOPATHY (HE), STUDIED BY SIMULTANEOUS EEG SPECTRAL ANALYSIS AND IN VIVO IH-NMR SPECTROSCOPY (NMRS).

NEP Deutz, AA de Graaf x, JG de Haan, WMMJ Boyle x, RAFM Chamuleau Lab. Exp. Medicine, Academic Medical Center, University of Amsterdam, Amsterdam and XDelft University of Technology, Dept. of Appl. Physics, Delft, The Netherlands.

The role of ammonia in the pathogenesis of acute HE is still not fully understood. Therefore we investigated EEG and ]H-NMRS changes in 3 models: I. acute liver ischemia; 2, inhibition of glutamine synthetase (GS) and 3. urease induced hyperammonemia. Male Wistar Rats (250-300g) with a chronically implanted NMR surface coil were used. At t=O h, acute HE was induced by liver ischemia (n=4); GS inhibition by i.p. injection of L- Methionine-DL-Sulfoximine (MSO, lO0 mg/kg b.w. n=4) and hyperammonemia by urease injection i.p. 1250 Units/kg b.w. (n=4). Cerebral changes in the rats were followed for at least 7h. The EEG left index (ratio between low and high frequency power) was used to monitor the severity of the encephalopathy and in vivo localised IH-N~S was used to measure the changes in relative concentrations of glutamine ~in], glutamate ~lu] and lactate ~ac.] in the brain by means of peak height determination. Results: In all 3 models - comparable changes in the level of consciousness, EEG left shift and decrease of the ~lu] were observed. During acute HE and after urease injection an in- crease of the [Glnj, followed by an increase of the [La~ was seen. Although increase in brain a,mlonia is present in all three models a one to one relationship between brain ammonia (biochemically determined) and the reported changes was not found. Nevertheless we believe ammonia to play an important role in the induction of the reported cerebral changes; alteration of Glu neurotransmission might be the common pathway.

48 SEGMENTAL TUBULAR Na + HANDLING IN PATIENTS WITH LIVER CIRRHOSIS AND ASCITES

J. Dfez, M. A. Simdn, F. Indart, A. Purroy, J. Prieto Department of Medicine, Unlversity Clinlc, Pamplona, Spain

Lithium (Li +) clearance has been advanced as an indlcator of Na + delivery from the proxi- mal tubules.To investigate the segmental tubular Na + handling in cirrhosis,the fractional proximal (FPRNa+) and distal (FDRNa +) Na + reabsorption were calculated from Li + clearance in 13 healthy controls,and 20 cirrhotic patients with ascites and normal creatinine clearance. All subjects were given a diet containing 40 mmol per day of Na + during 4 days before the study was performed.None of the patients were under pharmacological treatment during 2 weeks prior to the study.The mean (+SEM) values of fractional Li + clearance were lower (P,0.005) in patients (8.4+1.1%) than in controls (19+2.6%).FPRNa + was increased (P,0.005) in patients (91.2~1.6%) as c~mpared to controls (79.4~272%).No differences were found in FDRNa + between controls and patients as whole groups.However,when patients were separated into two groups according to their Na + balance,it was found that FDRNa + was increased in patients whose Na + balance remained positlve as compared to patients on a negative Na + balance (98.6+0.4 vs

94.2+l.5%,P(0.01).In addition,patients on a positive Na + balance exhibited higher--(P(0.02) plasmatic levels of aldosterone (260~79.2 pg/ml) than patients on a negative Na + balance (46.5~11.4 pg/ml).No differences were found in FPRNa+ between the two groups of patients. We conclude that proximal Na + reabsorption is stimulated in clrrhotic patients with ascltes, irrespectively of their natriuretic response to an restricted Na + diet. In contrast,an enhan- ced distal Na + reabsorption is only present in those patients which exhibit an avid Na + re- tention. Aldosterone appears to be one of the factors involved in the different tubular Na + handling of these two groups of cirrhotic patients.

$26