Intensive Care Unit Muscle Wasting: Skeletal Muscle Phenotype and Underlying Molecular Mechanisms

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Aare, Sudhakar Reddy,1978-Uppsala universitet,Klinisk neurofysiologi (författare)

Intensive Care Unit Muscle Wasting : Skeletal Muscle Phenotype and Underlying Molecular Mechanisms

BokEngelska2012

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Uppsala :Acta Universitatis Upsaliensis,2012
66 s.
electronicrdacarrier

Nummerbeteckningar

LIBRIS-ID:oai:DiVA.org:uu-180374
ISBN:9789155484699
https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-180374URI

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Språk:engelska
Sammanfattning på:engelska

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Ämneskategori:dok swepub-publicationtype

Serie

Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine,1651-6206 ;812

Anmärkningar

Acute quadriplegic myopathy (AQM), or critical illness myopathy, is a common debilitating acquired disorder in critically ill intensive care unit (ICU) patients characterized by generalized muscle wasting and weakness of limb and trunk muscles. A preferential loss of the thick filament protein myosin is considered pathognomonic of this disorder, but the myosin loss is observed relatively late during the disease progression. In attempt to explore the potential role of factors considered triggering AQM in sedated mechanically ventilated (MV) ICU patients, we have studied the early effects, prior to the myosin loss, of neuromuscular blockade (NMB), corticosteroids (CS) and sepsis separate or in combination in a porcine experimental ICU model. Specific interest has been focused on skeletal muscle gene/protein expression and regulation of muscle contraction at the muscle fiber level. This project aims at improving our understanding of the molecular mechanisms underlying muscle specific differences in response to the ICU intervention and the role played by the different triggering factors.The sparing of masticatory muscle fiber function was coupled to an up-regulation of heat shock protein genes and down-regulation of myostatin are suggested to be key factors in the relative sparing of masticatory muscles. Up-regulation of chemokine activity genes and down-regulation of heat shock protein genes play a significant role in the limb muscle dysfunction associated with sepsis. The effects of corticosteroids in the development of limb muscle weakness reveals up-regulation of kinase activity and transcriptional regulation genes and the down-regulation of heat shock protein, sarcomeric, cytoskeletal and oxidative stress responsive genes. In contrast to limb and craniofacial muscles, the respiratory diaphragm muscle responded differently to the different triggering factors. MV itself appears to play a major role for the diaphragm muscle dysfunction. By targeting these genes, future experiments can give an insight into the development of innovative treatments expected at protecting muscle mass and function in critically ill ICU patients.

Ämnesord och genrebeteckningar

MEDICIN OCH HÄLSOVETENSKAP Medicinska och farmaceutiska grundvetenskaper Neurovetenskaper hsv//swe
MEDICAL AND HEALTH SCIENCES Basic Medicine Neurosciences hsv//eng
acute quadriplegic myopathy
gene expression
myosin
heat shock proteins
mechanical ventilation
myostatin
sepsis
corticosteroids
diaphragm
Clinical Neurophysiology
Klinisk neurofysiologi

Biuppslag (personer, institutioner, konferenser, titlar ...)

Lars, LarssonUppsala universitet,Klinisk neurofysiologi (preses)
Olav, RooyackersKarolinska Inistitute, Department of Clinical Science, Intervention and Technology (opponent)
Uppsala universitetKlinisk neurofysiologi (creator_code:org_t)

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Av författaren/redakt...: Aare, Sudhakar R ...; Lars, Larsson; Olav, Rooyackers

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MEDICIN OCH HÄLSOVETENSKAP: MEDICIN OCH HÄLS ...; och Medicinska och f ...; och Neurovetenskaper

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Av lärosätet: Uppsala universitet

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