Variability in Skeletal Muscle Protein Synthesis Rates in Critically Ill Patients (original) (raw)
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PLoS ONE, 2011
Background: Skeletal muscle mass is controlled by myostatin and Akt-dependent signaling on mammalian target of rapamycin (mTOR), glycogen synthase kinase 3b (GSK3b) and forkhead box O (FoxO) pathways, but it is unknown how these pathways are regulated in critically ill human muscle. To describe factors involved in muscle mass regulation, we investigated the phosphorylation and expression of key factors in these protein synthesis and breakdown signaling pathways in thigh skeletal muscle of critically ill intensive care unit (ICU) patients compared with healthy controls.
Nutrients
Sarcopenia in critically ill patients is a highly prevalent comorbidity. It is associated with a higher mortality rate, length of mechanical ventilation, and probability of being sent to a nursing home after the Intensive Care Unit (ICU). Despite the number of calories and proteins delivered, there is a complex network of signals of hormones and cytokines that affect muscle metabolism and its protein synthesis and breakdown in critically ill and chronic patients. To date, it is known that a higher number of proteins decreases mortality, but the exact amount needs to be clarified. This complex network of signals affects protein synthesis and breakdown. Some hormones regulate metabolism, such as insulin, insulin growth factor glucocorticoids, and growth hormone, whose secretion is affected by feeding states and inflammation. In addition, cytokines are involved, such as TNF-alpha and HIF-1. These hormones and cytokines have common pathways that activate muscle breakdown effectors, such...
Metabolic phenotype of skeletal muscle in early critical illness
Thorax, 2018
To characterise the sketetal muscle metabolic phenotype during early critical illness. Vastus lateralis muscle biopsies and serum samples (days 1 and 7) were obtained from 63 intensive care patients (59% male, 54.7±18.0 years, Acute Physiology and Chronic Health Evaluation II score 23.5±6.5). From day 1 to 7, there was a reduction in mitochondrial beta-oxidation enzyme concentrations, mitochondrial biogenesis markers (PGC1α messenger mRNA expression (-27.4CN (95% CI -123.9 to 14.3); n=23; p=0.025) and mitochondrial DNA copy number (-1859CN (IQR -5557-1325); n=35; p=0.032). Intramuscular ATP content was reduced compared tocompared with controls on day 1 (17.7mmol/kg /dry weight (dw) (95% CI 15.3 to 20.0) vs. 21.7 mmol/kg /dw (95% CI 20.4 to 22.9); p<0.001) and decreased over 7 days (-4.8 mmol/kg dw (IQR -8.0-1.2); n=33; p=0.001). In addition, the ratio of phosphorylated:total AMP-K (the bioenergetic sensor) increased (0.52 (IQR -0.09-2.6); n=31; p<0.001). There was an increase ...
Acute Skeletal Muscle Wasting in Critical Illness
JAMA, 2013
IMPORTANCE Survivors of critical illness demonstrate skeletal muscle wasting with associated functional impairment. OBJECTIVE To perform a comprehensive prospective characterization of skeletal muscle wasting, defining the pathogenic roles of altered protein synthesis and breakdown. DESIGN, SETTING, AND PARTICIPANTS Sixty-three critically ill patients (59% male; mean age: 54.7 years [95% CI, 50.0-59.6 years]) with an Acute Physiology and Chronic Health Evaluation II score of 23.5 (95% CI, 21.9-25.2) were prospectively recruited within 24 hours following intensive care unit (ICU) admission from August 2009 to April 2011 at a university teaching and a community hospital in England. Patients were recruited if older than 18 years and were anticipated to be intubated for longer than 48 hours, to spend more than 7 days in critical care, and to survive ICU stay.
Mechanisms for Muscle Health in the Critically Ill Patient
Critical care nursing quarterly, 2013
Human skeletal muscles are continually remodeled to match the function required of them. Diameter, strength, and vascular supply are altered when a muscle group experiences contraction and resistance. The purpose of this article is to describe selected muscle signaling pathways that contribute to muscle remodeling. Multiple factors affect the cellular and molecular remodeling of muscles and at least 2 of them-exercise and protein/calorie delivery-are under the direct care of intensive care unit (ICU) clinicians. Activating signaling pathways may promote preservation of muscle mass and function. Interventions to prevent muscle atrophy have potential to reduce ICU-acquired weakness and positively affect quality of life in survivors after ICU hospitalization. Exploring information generated by genomic and proteomic investigations about muscle signaling pathways can help the ICU clinician evaluate the benefits and risks of interventions to maintain muscle health early in critical illness.
Recent evidence suggests that a negative protein balance secondary to severe disease is associated with increased morbidity. A loss of total body protein is inevitable in this scenario, even with an aggressive nutritional approach, primarily due to the catabolism of skeletal muscle fibers. The ubiquitin-proteasome system is the primary metabolic and biochemical mechanism involved in this process; paradoxically, this system consumes adenosine triphosphate as its energy source. It is possible that a neutral protein balance in these clinical situations is important for improving outcomes and achieving the caloric goals estimated or measured by indirect calorimetry. Recent studies have suggested that the use of higher protein concentrations in nutritional therapy for critically ill patients may help to reduce mortality. The purpose of this study was to review some of the nutrition therapy principles related to protein metabolism, evaluate the main assertions of the guidelines of special...
The association of perturbed skeletal muscle metabolism with ICU acquired weakness (ICUAW) is not clear. We characterised temporal changes in skeletal muscle mitochondrial function, ATP concentration, and substrate utilisation during and up to 6 months post ICU admission in critically ill patients enrolled into a randomised controlled trial of functional electrical stimulation-assisted cycle ergometry (FESCE) vs. standard care. To delineate mechanisms underpinning ICUAW we also compared the expression of genes involved in skeletal muscle mitochondrial function and substrate utilisation in the critically ill patients to control groups that had either undergone elective surgery or leg immobilisation (i.e. muscle disuse). The main finding was that mitochondrial function did not change 7 days or 6 months after ICU admission and was not impacted by FESCE. However, a 20% reduction in muscle ATP content by day 7 of ICU stay persisted after 6 months and was associated with ICUAW. Moreover, ...
Hyperventilation Increases Muscle Protein Synthesis in Critically Ill Trauma Patients
Journal of Surgical Research, 2000
Background. Critically ill trauma patients are often in negative nitrogen balance and demonstrate advanced muscle protein wasting, which is in part due to a decrease in muscle protein synthesis. Previous studies have been performed on the relationship between pH and protein metabolism. Some evidence suggests that alkalosis might enhance protein synthesis. The purpose of the present study is to determine whether protein synthesis is increased in trauma patients who have a respiratory alkalosis from hyperventilation.