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Mitochondrial Function in an In Vitro Model of Skeletal Muscle of Patients With Protracted Critical Illness and Intensive Care Unit-Acquired Weakness

K. Jiroutková, A. Krajčová, J. Žiak, M. Fric, J. Gojda, V. Džupa, M. Kalous, J. Tůmová, J. Trnka, F. Duška,

. 2017 ; 41 (7) : 1213-1221. [pub] 20160629

Language English Country United States

Document type Journal Article

Persistent link   https://www.medvik.cz/link/bmc18025356

BACKGROUND: Functional mitochondria in skeletal muscle of patients with protracted critical illness and intensive care unit-acquired weakness are depleted, but remaining mitochondria have increased functional capacities of respiratory complexes II and III. This can be an adaptation to relative abundancy of fatty acid over glucose caused by insulin resistance. We hypothesized that the capacity of muscle mitochondria to oxidize fatty acid is increased in protracted critical illness. METHODS: We assessed fatty acid oxidation (FAO) and mitochondrial functional indices in vitro by using extracellular flux analysis in cultured myotubes obtained by isolating and culturing satellite cells from vastus lateralis muscle biopsy samples from patients with ICU-acquired weakness (n = 6) and age-matched healthy controls (n = 7). Bioenergetic measurements were performed at baseline and after 6 days of exposure to free fatty acids (FFAs). RESULTS: Mitochondrial density in myotubes from ICU patients was 69% of healthy controls ( P = .051). After adjustment to mitochondrial content, there were no differences in adenosine triphosphate (ATP) synthesis or the capacity and coupling of the respiratory chain. FAO capacity in ICU patients was 157% of FAO capacity in controls ( P = .015). In myotubes of ICU patients, unlike healthy controls, the exposure to FFA significantly ( P = .009) increased maximum respiratory chain capacity. CONCLUSION: In an in vitro model of skeletal muscle of patients with protracted critical illness, we have shown signs of adaptation to increased FAO. Even in the presence of glucose and insulin, elevation of FFAs in the extracellular environment increased maximal capacity of the respiratory chain.

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$a Jiroutková, Kateřina $u 1 Laboratory of Bioenergetics, Third Faculty of Medicine, Charles University in Prague, Prague, Czech Republic. 2 Anaesthesiology and Resuscitation Department, Cardiology Centre, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.
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$a Mitochondrial Function in an In Vitro Model of Skeletal Muscle of Patients With Protracted Critical Illness and Intensive Care Unit-Acquired Weakness / $c K. Jiroutková, A. Krajčová, J. Žiak, M. Fric, J. Gojda, V. Džupa, M. Kalous, J. Tůmová, J. Trnka, F. Duška,
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$a BACKGROUND: Functional mitochondria in skeletal muscle of patients with protracted critical illness and intensive care unit-acquired weakness are depleted, but remaining mitochondria have increased functional capacities of respiratory complexes II and III. This can be an adaptation to relative abundancy of fatty acid over glucose caused by insulin resistance. We hypothesized that the capacity of muscle mitochondria to oxidize fatty acid is increased in protracted critical illness. METHODS: We assessed fatty acid oxidation (FAO) and mitochondrial functional indices in vitro by using extracellular flux analysis in cultured myotubes obtained by isolating and culturing satellite cells from vastus lateralis muscle biopsy samples from patients with ICU-acquired weakness (n = 6) and age-matched healthy controls (n = 7). Bioenergetic measurements were performed at baseline and after 6 days of exposure to free fatty acids (FFAs). RESULTS: Mitochondrial density in myotubes from ICU patients was 69% of healthy controls ( P = .051). After adjustment to mitochondrial content, there were no differences in adenosine triphosphate (ATP) synthesis or the capacity and coupling of the respiratory chain. FAO capacity in ICU patients was 157% of FAO capacity in controls ( P = .015). In myotubes of ICU patients, unlike healthy controls, the exposure to FFA significantly ( P = .009) increased maximum respiratory chain capacity. CONCLUSION: In an in vitro model of skeletal muscle of patients with protracted critical illness, we have shown signs of adaptation to increased FAO. Even in the presence of glucose and insulin, elevation of FFAs in the extracellular environment increased maximal capacity of the respiratory chain.
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$a Krajčová, Adéla $u 1 Laboratory of Bioenergetics, Third Faculty of Medicine, Charles University in Prague, Prague, Czech Republic. 3 Department of Internal Medicine II, Kralovske Vinohrady University Hospital, Prague, Czech Republic.
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$a Žiak, Jakub $u 1 Laboratory of Bioenergetics, Third Faculty of Medicine, Charles University in Prague, Prague, Czech Republic.
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$a Fric, Michal $u 4 Department of Anaesthesia and Intensive Care Medicine, Královské Vinohrady University Hospital and Third Faculty of Medicine, Charles University, Prague, Czech Republic.
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$a Gojda, Jan $u 3 Department of Internal Medicine II, Kralovske Vinohrady University Hospital, Prague, Czech Republic.
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$a Džupa, Valér $u 5 Department of Orthopaedic Surgeries, Kralovske Vinohrady University Hospital, Prague, Czech Republic.
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$a Kalous, Martin $u 6 Department of Cell Biology, Faculty of Science, Charles University in Prague, Prague, Czech Republic.
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$a Tůmová, Jana $u 1 Laboratory of Bioenergetics, Third Faculty of Medicine, Charles University in Prague, Prague, Czech Republic.
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$a Trnka, Jan $u 1 Laboratory of Bioenergetics, Third Faculty of Medicine, Charles University in Prague, Prague, Czech Republic.
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$a Duška, František $u 1 Laboratory of Bioenergetics, Third Faculty of Medicine, Charles University in Prague, Prague, Czech Republic. 4 Department of Anaesthesia and Intensive Care Medicine, Královské Vinohrady University Hospital and Third Faculty of Medicine, Charles University, Prague, Czech Republic.
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