Branched-chain amino acids increase arterial blood ammonia in spite of enhanced intrinsic muscle ammonia metabolism in patients with cirrhosis and healthy subjects
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Branched-chain amino acids increase arterial blood ammonia in spite of enhanced intrinsic muscle ammonia metabolism in patients with cirrhosis and healthy subjects. / Dam, Gitte; Keiding, Susanne; Munk, Ole Lajord; Ott, Peter; Buhl, Mads; Vilstrup, Hendrik; Bak, Lasse Kristoffer; Waagepetersen, Helle Sønderby; Schousboe, Arne; Møller, Niels; Sørensen, Michael.
In: American Journal of Physiology: Gastrointestinal and Liver Physiology, Vol. 301, No. 2, 01.08.2011, p. G269-77.Research output: Contribution to journal › Journal article › Research › peer-review
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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 -
ID: 35134488