title: Branched-chain amino acids increase arterial blood ammonia in spite of enhanced intrinsic muscle ammonia metabolism in patients with cirrhosis and healthy subjects.
abstract: Branched-chain amino acids (BCAA) are used in attempts to reduce blood ammonia in patients with cirrhosis and intermittent hepatic encephalopathy based on the hypothesis that BCAA stimulate muscle ammonia detoxification. We studied the effects of an oral dose of BCAA on the skeletal muscle metabolism of ammonia and amino acids in 14 patients with cirrhosis and in 7 healthy subjects by combining [(13)N]ammonia positron emission tomography (PET) of the thigh muscle with measurements of blood flow and arteriovenous (A-V) concentrations of ammonia and amino acids. PET was used to measure the metabolism of blood-supplied ammonia and the A-V measurements were used to measure the total ammonia metabolism across the thigh muscle. After intake of BCAA, blood ammonia increased more than 30% in both groups of subjects (both P < 0.05). Muscle clearance of blood-supplied ammonia (PET) was unaffected (P = 0.75), but the metabolic removal rate (PET) increased significantly because of increased blood ammonia in both groups (all P < 0.05). The total ammonia clearance across the leg muscle (A-V) increased by more than 50% in both groups, and the flux (A-V) of ammonia increased by more than 45% (all P < 0.05). BCAA intake led to a massive glutamine release from the muscle (cirrhotic patients, P < 0.05; healthy subjects, P = 0.12). In conclusion, BCAA enhanced the intrinsic muscle metabolism of ammonia but not the metabolism of blood-supplied ammonia in both the patients with cirrhosis and in the healthy subjects.
authors.affiliation: PET Centre, Aarhus University Hospital, Denmark. dam@pet.auh.dk
authors.forename: Gitte
authors.initials: G
authors.lastname: Dam
authors.forename: Susanne
authors.initials: S
authors.lastname: Keiding
authors.forename: Ole Lajord
authors.initials: OL
authors.lastname: Munk
authors.forename: Peter
authors.initials: P
authors.lastname: Ott
authors.forename: Mads
authors.initials: M
authors.lastname: Buhl
authors.forename: Hendrik
authors.initials: H
authors.lastname: Vilstrup
authors.forename: Lasse Kristoffer
authors.initials: LK
authors.lastname: Bak
authors.forename: Helle Sønderby
authors.initials: HS
authors.lastname: Waagepetersen
authors.forename: Arne
authors.initials: A
authors.lastname: Schousboe
authors.forename: Niels
authors.initials: N
authors.lastname: Møller
authors.forename: Michael
authors.initials: M
authors.lastname: Sørensen
mesh_terms: D000597:Amino Acids, Branched-Chain / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D000641:Ammonia / Q000097:blood* / Q000493:pharmacokinetics; D005260:Female; D005263:Femoral Artery / Q000502:physiology; D005268:Femoral Vein / Q000502:physiology; D005973:Glutamine / Q000097:blood / Q000493:pharmacokinetics; D006801:Humans; D007532:Isoleucine / Q000097:blood / Q000493:pharmacokinetics; D007930:Leucine / Q000097:blood / Q000493:pharmacokinetics; D008104:Liver Cirrhosis, Alcoholic / Q000097:blood*; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism*; D049268:Positron-Emission Tomography; D017534:Radial Artery / Q000502:physiology; D012039:Regional Blood Flow / Q000187:drug effects; D013848:Thigh / Q000098:blood supply / Q000000981:diagnostic imaging; D014057:Tomography, X-Ray Computed; D014633:Valine / Q000097:blood / Q000493:pharmacokinetics
chemical_list: D000597:Amino Acids, Branched-Chain; D007532:Isoleucine; D005973:Glutamine; D000641:Ammonia; D007930:Leucine; D014633:Valine