Influence of branched‐chain amino acid infusion on arterial concentrations and brain exchange of amino acids in patients with hepatic cirrhosis

Abstract

Summary. The influence of branched‐chain amino acid (BCAA) infusion on arterial concentrations and brain exchange of amino acids was studied in seven patients with hepatic cirrhosis and in six healthy control subjects. Arterial levels and arterial‐jugular venous (A‐JV) concentration differences for amino acids, glucose, ketone bodies and lactate were measured in the basal state and during a constant rate, 150 min intravenous infusion of a BCAA solution (250 fmiol/min, 70% L‐leucine, 20% L‐valine and 10% L‐isoleucine). In the basal state the arterial whole blood concentrations of tyrosine, phenylalanine and methionine were 40–130 % higher in the cirrhotic patients compared to the controls, while the levels of the BCAA were 20–35 % lower. The patients' concentration of aspartic acid was 70% below the corresponding control value. During BCAA infusion the arterial leucine concentration rose 4–5 fold while valine increased 60–95% and isoleucine rose 45–50%. The arterial levels of several amino acids decreased progressively in a similar manner in patients and controls. At the end of the 150 min infusion period methionine had decreased 35% (P<001), tyrosine 25% (P<0–001) and phenylalanine 35% (P<0–001) in the patient group. Positive A‐JV differences in amino acid concentration–indicating net brain uptake–were seen for leucine, isoleucine, valine, serine, tyrosine and lysine in both groups in the basal state. The patients had a greater A‐JV difference than the controls for tyrosine (P<0–05) while the uptake of the other amino acids, including the BCAA, was similar in the two groups. The fractional uptake of leucine and valine was significantly increased in the patients. During BCAA infusion the A‐JV difference for leucine increased 2–3 fold in both patients and controls and the net uptake to the brain of tyrosine and phenylalanine was abolished in the patient group. It is concluded that (a) patients with hepatic cirrhosis show a decreased whole blood concentration of aspartate indicating a reduced intracellular concentration of this amino acid, (b) brain uptake of tyrosine and fractional uptake of leucine and valine is augmented in patients with hepatic cirrhosis, demonstrating abnormal brain amino acid uptake in this disorder, and (c) BCAA infusion effectively lowers the arterial concentrations for tyrosine, phenylalanine and methionine in cirrhotic patients as well as in healthy controls and blocks the abnormal brain uptake of tyrosine. These findings provide a biochemical background to the suggested beneficial effect of BCAA infusion in patients with hepatic cirrhosis and portal systemic encephalopathy.