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Title: Acute skeletal muscle wasting in the critically ill
Author: Puthucheary, Z. A.
ISNI:       0000 0004 5362 1353
Awarding Body: University College London (University of London)
Current Institution: University College London (University of London)
Date of Award: 2014
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Introduction: Critical illness survivors demonstrate skeletal muscle wasting with associated functional impairment. I prospectively characterised this process, and defined the pathogenic roles of altered protein synthesis and degradation. Methods: Critically ill patients (n=63, 59% male, age 54.7±18.0 years, APACHE II score 23.5±6.5) were recruited <24 hours following intensive care admission. Muscle loss trajectory was determined through serial ultrasound measurement of rectus femoris cross-sectional area (RFCSA) and, in a subset, quantification of myofibre area (FibreCSA) and protein/DNA ratio. Histopathological analysis was performed. Muscle protein synthesis and breakdown rates were determined and respective signalling pathways examined. Results: RFCSA decreased significantly, (-17.7±12.1%, [p<0.001]), underestimating muscle loss determined by FibreCSA (-10.3±10.9% vs.-17.5±30.2%, p=0.31), or protein/DNA ratio (-10.3±10.9% vs. -29.5±41.5%, p=0.03). Fall in RFCSA was greater in multi- than single-organ failure (-21.5±10.5% vs. - 7.2± 9.7%, p <0.0001), even by day 3 (-8.7±16.3% vs. -1.8± 9.6%, p<0.01). Myofibre necrosis occurred in >50% (20/37) of subjects. Protein synthesis was depressed to levels observed in fasted controls (0.035±0.018%/hr vs. 0.039±0.011%/hr, p=0.57), and increased by day 7 (0.076±0.066%/hr, p=0.03) to levels associated with fed controls (0.065+0.018%/hr, p=0.30,) independent of nutritional load. Protein breakdown remained elevated throughout (8.5±5.7 to 10.6±5.7mmol phe/min/IBW, p=0.4).Principal component analysis of intracellular signalling supported a programme of increased breakdown (r=-0.83, p=0.005) and depressed synthesis (r=-.69, p=0.041). Conclusions: Early rapid skeletal muscle wasting occurs in critical illness, is greatest in those with multi-organ failure, and results from suppression of protein synthesis and increases in catabolism. These effects are independent of feeding and are commonly associated with myonecrosis.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available