ArticleAmerican journal of physiology. Gastrointestinal and liver physiology2016
Hyperammonemia results in reduced muscle function independent of muscle mass.
Article in American journal of physiology. Gastrointestinal and liver physiology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 73 citations in OpenAlex.
- Hyaluronan 35 prevents endotoxin-mediated dysregulated skeletal muscle proteostasis during ethanol exposure.American journal of physiology. Endocrinology and metabolism · 2026Article
- Combination of Frailty and Sarcopenia Predicts Peri-operative Outcomes in Patients Undergoing Liver Transplantation: Analysis of the National Inpatient Sample.Digestive diseases and sciences · 2025Article
- Voluntary Activity Wheel Running Improves Hyperammonaemia-Induced Skeletal Muscle Molecular and Metabolic Perturbations in Mice.Journal of cachexia, sarcopenia and muscle · 2025Article
- Ultrasound-Defined Sarcopenia Independently Predicts Acute Decompensation in Advanced Chronic Liver Disease.Journal of cachexia, sarcopenia and muscle · 2024Article
- Ammonia-induced stress response in liver disease progression and hepatic encephalopathy.Nature reviews. Gastroenterology & hepatology · 2024Review
- Clinical practice guidelines for nutritional assessment and monitoring of adult ICU patients in China.Journal of intensive medicine · 2024Article
- L-Isoleucine reverses hyperammonemia-induced myotube mitochondrial dysfunction and post-mitotic senescence.The Journal of nutritional biochemistry · 2024Article
- Multiple ammonia-induced episodes of hepatic encephalopathy provoke neuronal cell loss in bile-duct ligated rats.JHEP reports : innovation in hepatology · 2023Article
- Aspartic Acid in Health and Disease.Nutrients · 2023Review
- Liver transplantation in the patient with physical frailty.Journal of hepatology · 2023Review
- Diet was less significant than physical activity in the prognosis of people with sarcopenia and metabolic dysfunction-associated fatty liver diseases: Analysis of the National Health and Nutrition Examination Survey III.Frontiers in endocrinology · 2023Article
- Shared and unique phosphoproteomics responses in skeletal muscle from exercise models and in hyperammonemic myotubes.iScience · 2022Article
- Muscle Amino Acid and Adenine Nucleotide Metabolism during Exercise and in Liver Cirrhosis: Speculations on How to Reduce the Harmful Effects of Ammonia.Metabolites · 2022Review
- Nutritional priorities in patients with severe COVID-19.Current opinion in clinical nutrition and metabolic care · 2022Review
- Ammonia and the Muscle: An Emerging Point of View on Hepatic Encephalopathy.Journal of clinical medicine · 2022Review
- Implications of pre-transplant sarcopenia and frailty in patients with non-alcoholic steatohepatitis and alcoholic liver disease.Translational gastroenterology and hepatology · 2022Review
- Impact of L-ornithine L-aspartate on non-alcoholic steatohepatitis-associated hyperammonemia and muscle alterations.Frontiers in nutrition · 2022Article
- Metabolic reprogramming during hyperammonemia targets mitochondrial function and postmitotic senescence.JCI insight · 2021Article
- An Overview of the Molecular Mechanisms Contributing to Musculoskeletal Disorders in Chronic Liver Disease: Osteoporosis, Sarcopenia, and Osteoporotic Sarcopenia.International journal of molecular sciences · 2021Review
- Compound Sarcopenia in Hospitalized Patients with Cirrhosis Worsens Outcomes with Increasing Age.Nutrients · 2021Article
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
The mechanism of the nearly universal decreased muscle strength in cirrhosis is not known. We evaluated whether hyperammonemia in cirrhosis causes contractile dysfunction independent of reduced skeletal muscle mass. Maximum grip strength and muscle fatigue response were determined in cirrhotic patients and controls. Blood and muscle ammonia concentrations and grip strength normalized to lean body mass were measured in the portacaval anastomosis (PCA) and sham-operated pair-fed control rats (n = 5 each). Ex vivo contractile studies in the soleus muscle from a separate group of Sprague-Dawley rats (n = 7) were performed. Skeletal muscle force of contraction, rate of force development, and rate of relaxation were measured. Muscles were also subjected to a series of pulse trains at a range of stimulation frequencies from 20 to 110 Hz. Cirrhotic patients had lower maximum grip strength and greater muscle fatigue than control subjects. PCA rats had a 52.7 ± 13% lower normalized grip strength compared with control rats, and grip strength correlated with the blood and muscle ammonia concentrations (r(2) = 0.82). In ex vivo muscle preparations following a single pulse, the maximal force, rate of force development, and rate of relaxation were 12.1 ± 3.5 g vs. 6.2 ± 2.1 g; 398.2 ± 100.4 g/s vs. 163.8 ± 97.4 g/s; -101.2 ± 22.2 g/s vs. -33.6 ± 22.3 g/s in ammonia-treated compared with control muscle preparation, respectively (P < 0.001 for all comparisons). Tetanic force, rate of force development, and rate of relaxation were depressed across a range of stimulation from 20 to 110 Hz. These data provide the first direct evidence that hyperammonemia impairs skeletal muscle strength and increased muscle fatigue and identifies a potential therapeutic target in cirrhotic patients.
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