Ammonia metabolism in chronic obstructive pulmonary disease with special reference to congestive right ventricular failure

Valero, Andrea Romero; Alroy, G; Eisenkraft, B.; Itskovitch, J.

doi:10.1136/thx.29.6.703

Cited by 12 publications

(8 citation statements)

References 14 publications

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“…When T-scores were used, 12 patients (28.6%) scored at the impairment level on 1 or more tests. Six were mildly impaired (T-score, [30][31][32][33][34][35], and 6 were moderately severely impaired (T-score, <30). Four patients scored less than 35 on the Commands subtest, 3 on the MMSE, 6 on the Draw-a-Clock Test, and 4 on the Complex Ideational Material subtest.…”

Section: Resultsmentioning

confidence: 99%

“…[22][23][24][25][26][27][28] In studies of patients with heart failure who have measurable cognitive impairment, fluid overload is typically speculated to be the cause. 14,15,19,20,22,[29][30][31] Age 22 and education 22,32 also have been associated with cognitive impairment. Low-output states such as systemic hypotension 21 and low ejection fraction 23 also have been implicated as causes of cognitive impairment in patients with heart failure.…”

Section: • Objectives To Describe Cognitive Impairment In Patients Wimentioning

confidence: 99%

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Cognitive Impairment in Heart Failure: Issues of Measurement and Etiology

Riegel

Bennett

Davis

et al. 2002

American Journal of Critical Care

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• Background Clinicians need easy methods of screening for cognitive impairment in patients with heart failure. If correlates of cognitive impairment could be identified, more patients with early cognitive impairment could be treated before the problem interfered with adherence to treatment. • Objectives To describe cognitive impairment in patients with heart failure, to explore the usefulness of 4 measures of cognitive impairment, and to assess correlates of cognitive impairment. • Methods A descriptive, correlational design was used. Four screening measures of cognition were assessed in 42 patients with heart failure: Commands subtest and Complex Ideational Material subtest of the Boston Diagnostic Aphasia Examination, Mini-Mental State Examination, and Draw-a-Clock Test. Cognitive impairment was defined as performance less than the standardized (T-score) cutoff point on at least 1 of the 4 measures. Possible correlates of cognitive impairment included age, education, hypotension, fluid overload (serum osmolality <269 mOsm/kg), and dehydration (serum osmolality ≥295 mOsm/kg). • Results Cognitive impairment was detected in 12 (28.6%) of 42 participants. The 4 screening tests varied in effectiveness, but the Draw-a-Clock Test indicated impairment in 50% of the 12 impaired patients. A summed standardized score for the 4 measures was not significantly associated with age, education, hypotension, fluid overload, or dehydration in this sample. • Conclusions Cognitive impairment is relatively common in patients with heart failure. The Draw-a-Clock Test was most useful in detecting cognitive impairment, although it cannot be used to detect problems with verbal learning or delayed recall and should not be used as the sole screening method for patients with heart failure. Correlates of cognitive impairment require further study.

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Section: Resultsmentioning

confidence: 99%

Section: • Objectives To Describe Cognitive Impairment In Patients Wimentioning

confidence: 99%

Cognitive Impairment in Heart Failure: Issues of Measurement and Etiology

Riegel

Bennett

Davis

et al. 2002

American Journal of Critical Care

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“…Sarcopenia or loss of skeletal muscle mass is a frequent complication of cirrhosis, advanced heart failure, and chronic lung disease that adversely impacts outcomes . Despite the high clinical significance, there are limited data on the mechanisms of sarcopenia and consequently a lack of effective therapies .…”

mentioning

confidence: 99%

“…S arcopenia or loss of skeletal muscle mass is a frequent complication of cirrhosis, advanced heart failure, and chronic lung disease that adversely impacts outcomes. (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12) Despite the high clinical significance, there are limited data on the mechanisms of sarcopenia and consequently a lack of effective therapies. (3) Hyperammonemia is a consistent abnormality in cirrhosis due to impaired ureagenesis capacity and portosystemic shunting.…”

mentioning

confidence: 99%

Ammonia lowering reverses sarcopenia of cirrhosis by restoring skeletal muscle proteostasis

Kumar¹,

Davuluri²,

Silva³

et al. 2017

Hepatology

174

151

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Sarcopenia or skeletal muscle loss is a frequent, potentially reversible complication in cirrhosis that adversely affects clinical outcomes. Hyperammonemia is a consistent abnormality in cirrhosis that results in impaired skeletal muscle protein synthesis and breakdown (proteostasis). Despite availability of effective ammonia lowering therapies, whether lowering ammonia restores proteostasis and reverses muscle mass is unknown. Myotube diameter, protein synthesis and molecular responses in C2C12 murine myotubes to withdrawal of ammonium acetate following 24 h exposure to 10mM ammonium acetate were complemented by in vivo studies in the hyperammonemic portacaval anastomosis rat (PCA) and sham operated, pair-fed (SO) Sprague- Dawley rats treated with ammonia lowering therapy by L-ornithine L-aspartate and rifaximin orally for 4 weeks. We observed reduced myotube diameter, impaired protein synthesis and increased autophagy flux in response to hyperammonemia that were partially reversed following 24h and 48h withdrawal of ammonium acetate. Consistently, 4 weeks of ammonia lowering therapy resulted in significant lowering of blood and skeletal muscle ammonia, increase in lean body mass, improved grip strength and higher skeletal muscle mass, diameter and an increase in type II fibers in the treated compared to untreated PCA rats. Increased skeletal muscle myostatin expression, reduced mTORC1 function, and the hyperammonemic stress response including autophagy markers were also reversed in the PCA rats treated with ammonia lowering therapy. Despite significant improvement, molecular and functional readouts were not completely reversed by ammonia lowering measures. Conclusions Ammonia lowering therapy results in improvement in skeletal muscle phenotype, function and molecular perturbations of hyperammonemia. These preclinical studies complement previous studies on ammonia induced skeletal muscle loss and lay the foundation for prolonged ammonia lowering therapy to reverse sarcopenia of cirrhosis.

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“…Ammonia, an endogenous cytotoxin generated during amino acid and purine nucleotide catabolism and the gut microbiome, is metabolized to urea in hepatocytes ( Adeva et al., 2012 ; Dasarathy and Hatzoglou, 2018 ). Dysregulated ammonia metabolism occurs in a number of chronic diseases, including liver cirrhosis, heart failure, and chronic obstructive pulmonary disease ( Dasarathy and Hatzoglou, 2018 ; Medeiros et al., 2014 ; Valero et al., 1974 ). During the consequent hyperammonemia, skeletal muscle becomes a major organ for ammonia uptake ( Ganda and Ruderman, 1976 ; Lockwood et al., 1979 ; Qiu et al., 2013 ) with complex molecular and metabolic perturbations( Dasarathy and Hatzoglou, 2018 ; Davuluri et al., 2016a , 2016b ; Kumar et al., 2021 ; Medeiros et al., 2014 ; Valero et al., 1974 ; Welch et al., 2021 ).…”

Section: Introductionmentioning

confidence: 99%