Session Title: Category 2b. CIRRHOSIS AND ITS COMPLICATIONS: b. CLINICAL ASPECTS
Presentation Date: Apr 15, 2010
EFFECT OF BRANCHED-CHAIN AMINO ACIDS ON AMMONIA METABOLISM IN SKELETAL MUSCLE IN PATIENTS WITH LIVER CIRRHOSIS AND HEALTHY CONTROLS MEASURED BY 13N-AMMONIA PET
G. Dam1,2*, O.L. Munk1, P. Ott2, S. Keiding1,2, M. Sørensen1,2
1PET Centre, Aarhus University Hospital, Aarhus C, 2Department of Medicine V, Aarhus University Hospital, Aarhus, Denmark. *email@example.com
Background and aims: Branched-chain amino acids (BCAA; leucine, valine, isoleucine) are widely used to prevent hepatic encephalopathy in patients with liver cirrhosis. The main effect of BCAA is believed to take place in muscles where they provide carbon-skeletons for the TCA-cycle. This should enhance the conversion of alfa-ketoglutarate and ammonia to glutamine, thereby lowering the blood concentration of ammonia. We studied the effect of oral administered BCAA on the metabolism of ammonia in thigh muscle of patients with cirrhosis and healthy subjects by 13N-ammonia PET.
Methods: After overnight fasting, 5 patients with cirrhosis and 5 healthy subjects underwent PET-scans of the thighs before and 2 hours after an oral load of BCAA (0.45 g BCAA/kg body weight). Following i.v. injection of 13N-ammonia, PET recording of the thighs was performed with simultaneous blood sampling from a radial artery for determination of blood concentrations of 13N-ammonia, 13N-metabolites, ammonia (ca) and amino acids. Data was analyzed by non-linear regression analysis and the net metabolic clearance of 13N-ammonia, K, calculated. The removal rate of ammonia, v, was calculated as K ca.
Results: The blood concentrations of BCAA increased equally and significantly in both patients and healthy controls. Baseline arterial concentration of ammonia was significantly higher in patients than in healthy controls (mean, 129 vs. 62 µmol/l, p< 0.05) and increased significantly in both groups (mean, 157 vs. 93 µmol/l, p< 0.05). At baseline, the net metabolic clearance, K, of ammonia was not significantly different between patients and healthy subjects (both 0.03 ml blood/ml tissue/min). In neither of the groups did K change significantly following BCAA (0.04 in patients; 0.03 in healthy subjects). The mean baseline removal rate of ammonia was higher in patients than in healthy subjects (3.40 vs. 1.54 µmol/ml tissue/min, p< 0.05) and increased to 6.00 and 2.76 µmol/ml tissue/min, respectively (both p< 0.05).
Conclusions: Oral administration of BCAA led to an increased removal rate of ammonia in muscle tissue but no changes in intrinsic ammonia kinetics. Accordingly, the increased removal seems to be a response to the increase in blood ammonia and not due to induction of intrinsic ammonia removal.