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.

Anaesthesiology and Resuscitation Department Cardiology Centre Institute for Clinical and Experimental Medicine Prague Czech Republic

Department of Anaesthesia and Intensive Care Medicine Královské Vinohrady University Hospital and 3rd Faculty of Medicine Charles University Prague Czech Republic

Department of Cell Biology Faculty of Science Charles University Prague Prague Czech Republic

Department of Internal Medicine 2 Kralovske Vinohrady University Hospital Prague Czech Republic

Department of Orthopaedic Surgeries Kralovske Vinohrady University Hospital Prague Czech Republic

Laboratory of Bioenergetics 3rd Faculty of Medicine Charles University Prague Prague Czech Republic

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Functional electrical stimulation-assisted cycle ergometry in the critically ill: protocol for a randomized controlled trial