The Effect of Nutritional Status in the Pathogenesis of Critical Illness Myopathy (CIM)

Ogilvie, Hannah; Larsson, Lars

doi:10.3390/biology3020368

Cited by 4 publications

(7 citation statements)

References 49 publications

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“…Numerous factors, most notably muscle unloading during bedrest, insufficient nutrition, pharmacologic exposures, and imbalanced protein catabolism and synthesis, have been shown to contribute to sepsis-mediated atrophy (Schefold et al, 2010; Schreiber et al, 2018; Eikermann et al, 2006; Spranger et al, 2003; Dres et al, 2017; Yu et al, 2018; Lang et al, 2007; Yang et al, 2018; Vary and Kimball, 1992; Puthucheary et al, 2013; Bouglé et al, 2016). However, clinical interventions with early mobilization (Denehy et al, 2013; Morris et al, 2016; Moss et al, 2016; Tipping et al, 2017) and nutritional support (Goossens et al, 2017; Hermans et al, 2013; Ogilvie and Larsson, 2014) have not improved long-term outcomes, and some studies even show negative effects of high protein delivery on muscle wasting (Puthucheary et al, 2013). Beyond this key issue, muscle weakness is not always accompanied by muscle wasting: they are separate entities that should not be considered synonymously (Schefold et al, 2010; Reid and Moylan, 2011).…”

Section: Discussionmentioning

confidence: 99%

Chronic muscle weakness and mitochondrial dysfunction in the absence of sustained atrophy in a preclinical sepsis model

Owen

Patel

Smith

et al. 2019

eLife

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Chronic critical illness is a global clinical issue affecting millions of sepsis survivors annually. Survivors report chronic skeletal muscle weakness and development of new functional limitations that persist for years. To delineate mechanisms of sepsis-induced chronic weakness, we first surpassed a critical barrier by establishing a murine model of sepsis with ICU-like interventions that allows for the study of survivors. We show that sepsis survivors have profound weakness for at least 1 month, even after recovery of muscle mass. Abnormal mitochondrial ultrastructure, impaired respiration and electron transport chain activities, and persistent protein oxidative damage were evident in the muscle of survivors. Our data suggest that sustained mitochondrial dysfunction, rather than atrophy alone, underlies chronic sepsis-induced muscle weakness. This study emphasizes that conventional efforts that aim to recover muscle quantity will likely remain ineffective for regaining strength and improving quality of life after sepsis until deficiencies in muscle quality are addressed.

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Section: Discussionmentioning

confidence: 99%

Chronic muscle weakness and mitochondrial dysfunction in the absence of sustained atrophy in a preclinical sepsis model

Owen

Patel

Smith

et al. 2019

eLife

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“…Nutritional status is another important factor in the treatment of critically ill ICU patients, but the role of nutrition in the pathogenesis of CIM remains unknown. In an attempt to study the effects of caloric intake in the pathogenesis of CIM, limb muscles were compared between animals given low versus eucaloric parenteral feeding (523). However, the preferential myosin loss, decline in specific force, and muscle fiber atrophy did not differ between low and eucaloric animals.…”

Section: Rodent Icu Modelmentioning

confidence: 99%

“…Furthermore, passive mechanical loading had a sparing effect on muscle weight independent of nutritional status. Thus the mechanical silencing associated with the ICU condition is forwarded as a stronger trigger factor than nutritional status in the pathogenesis of CIM (523).…”

Section: Rodent Icu Modelmentioning

confidence: 99%

The Sick and the Weak: Neuropathies/Myopathies in the Critically Ill

Friedrich

Reid

Berghe

et al. 2015

Physiological Reviews

291

329

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Critical illness polyneuropathies (CIP) and myopathies (CIM) are common complications of critical illness. Several weakness syndromes are summarized under the term intensive care unit-acquired weakness (ICUAW). We propose a classification of different ICUAW forms (CIM, CIP, sepsis-induced, steroid-denervation myopathy) and pathophysiological mechanisms from clinical and animal model data. Triggers include sepsis, mechanical ventilation, muscle unloading, steroid treatment, or denervation. Some ICUAW forms require stringent diagnostic features; CIM is marked by membrane hypoexcitability, severe atrophy, preferential myosin loss, ultrastructural alterations, and inadequate autophagy activation while myopathies in pure sepsis do not reproduce marked myosin loss. Reduced membrane excitability results from depolarization and ion channel dysfunction. Mitochondrial dysfunction contributes to energy-dependent processes. Ubiquitin proteasome and calpain activation trigger muscle proteolysis and atrophy while protein synthesis is impaired. Myosin loss is more pronounced than actin loss in CIM. Protein quality control is altered by inadequate autophagy. Ca 2ϩ dysregulation is present through altered Ca 2ϩ homeostasis. We highlight clinical hallmarks, trigger factors, and potential mechanisms from human studies and animal models that allow separation of risk factors that may trigger distinct mechanisms contributing to weakness. During critical illness, altered inflammatory (cytokines) and metabolic pathways deteriorate muscle function. ICUAW prevention/treatment is limited, e.g., tight glycemic control, delaying nutrition, and early mobilization. Future challenges include identification of primary/secondary events during the time course of critical illness, the interplay between membrane excitability, bioenergetic failure and differential proteolysis, and finding new therapeutic targets by help of tailored animal models.

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“…Organizmada yaşamsal fonksiyonların ve hücre metabolizmasının sürdürülmesi enerji gerektiren olaylardır (1). İnsan vücudunda doku yıkımı ve yapımı aynı anda gerçekleşebilen ve dengeli bir biçimde sürdürülebilen bir süreçtir.…”

Section: Introductionunclassified

“…Normal koşullarda bu ihtiyaç, doğal yollardan beslenme ile sağlanabilir. Yoğun bakımda ise bu mümkün olamayacağından, bu eksiklikler ancak klinik nütrisyon uygulanmasıyla giderilebilir (1)(2)(3)(4).…”

Section: Introductionunclassified