TY - JOUR

T1 - Branched-chain amino acids increase arterial blood ammonia in spite of enhanced intrinsic muscle ammonia metabolism in patients with cirrhosis and healthy subjects

AU - Dam, Gitte

AU - Keiding, Susanne

AU - Munk, Ole Lajord

AU - Ott, Peter

AU - Buhl, Mads

AU - Vilstrup, Hendrik

AU - Bak, Lasse Kristoffer

AU - Waagepetersen, Helle Sønderby

AU - Schousboe, Arne

AU - Møller, Niels

AU - Sørensen, Michael

PY - 2011/8/1

Y1 - 2011/8/1

N2 - 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.

AB - 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.

KW - Amino Acids, Branched-Chain

KW - Ammonia

KW - Female

KW - Femoral Artery

KW - Femoral Vein

KW - Glutamine

KW - Humans

KW - Isoleucine

KW - Leucine

KW - Liver Cirrhosis, Alcoholic

KW - Male

KW - Metabolic Clearance Rate

KW - Middle Aged

KW - Muscle, Skeletal

KW - Positron-Emission Tomography

KW - Radial Artery

KW - Regional Blood Flow

KW - Thigh

KW - Tomography, X-Ray Computed

KW - Valine

KW - Former Faculty of Pharmaceutical Sciences

U2 - 10.1152/ajpgi.00062.2011

DO - 10.1152/ajpgi.00062.2011

M3 - Journal article

C2 - 21636533

VL - 301

SP - G269-77

JO - American Journal of Physiology: Gastrointestinal and Liver Physiology

JF - American Journal of Physiology: Gastrointestinal and Liver Physiology

SN - 0193-1857

IS - 2

ER -