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The Intensive Care Unit-Acquired Weakness: the role of mitochondrial dysfunction in its pathogenesis
Jiroutková, Kateřina ; Duška, František (advisor) ; Houštěk, Josef (referee) ; Maňák, Jan (referee)
BACKGROUND: ICU-acquired weakness impairs functional outcome in survivors of critical illness. Therefore, deepening our understanding of its pathogenesis is an important goal as muscle-specific therapeutic targets are urgently needed. Systemic inflammation and sepsis are the main risk factors of ICUAW, and these syndromes are associated with mitochondrial dysfunction. The aim of our study was to collect reliable information on the mitochondrial function of human skeletal muscle in the protracted phase of critical illness. Additionally, we explored mitochondrial respiratory parameters following experimentally induced changes in the availability or composition of selected nutrients (fatty acids and glutamine). MATERIALS and METHODS: Vastus lateralis muscle biopsy samples from patients with ICU- acquired weakness and age-matched healthy controls were obtained. In human skeletal muscle tissue homogenates mitochondrial functional indices were assessed by high- resolution respirometry, individual functional capacities of respiratory complexes were measured by spectrophotometry and correlated with concentrations of electron transport chain key subunits measured by western blot. Additionally, using human myoblasts and myotubes we studied the influence of extracellular environment manipulations by...
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The Intensive Care Unit-Acquired Weakness: the role of mitochondrial dysfunction in its pathogenesis
Jiroutková, Kateřina ; Duška, František (advisor) ; Houštěk, Josef (referee) ; Maňák, Jan (referee)
BACKGROUND: ICU-acquired weakness impairs functional outcome in survivors of critical illness. Therefore, deepening our understanding of its pathogenesis is an important goal as muscle-specific therapeutic targets are urgently needed. Systemic inflammation and sepsis are the main risk factors of ICUAW, and these syndromes are associated with mitochondrial dysfunction. The aim of our study was to collect reliable information on the mitochondrial function of human skeletal muscle in the protracted phase of critical illness. Additionally, we explored mitochondrial respiratory parameters following experimentally induced changes in the availability or composition of selected nutrients (fatty acids and glutamine). MATERIALS and METHODS: Vastus lateralis muscle biopsy samples from patients with ICU- acquired weakness and age-matched healthy controls were obtained. In human skeletal muscle tissue homogenates mitochondrial functional indices were assessed by high- resolution respirometry, individual functional capacities of respiratory complexes were measured by spectrophotometry and correlated with concentrations of electron transport chain key subunits measured by western blot. Additionally, using human myoblasts and myotubes we studied the influence of extracellular environment manipulations by...
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