Trumbeckaite 2001 Eur J Biochem

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Trumbeckaite S, Opalka JR, Neuhof C, Zierz S, Gellerich FN (2001) Different sensitivity of rabbit heart and skeletal muscle to endotoxin-induced impairment of mitochondrial function. Eur J Biochem 268:1422-9.

» PMID: 11231295

Trumbeckaite S, Opalka JR, Neuhof C, Zierz S, Gellerich FN (2001) Eur J Biochem

Abstract: The involvement of mitochondrial dysfunction in septic disturbances of tissues is controversial. The aim of this study was to investigate the effects of endotoxininduced sepsis on the function of heart and skeletal muscle mitochondria. Rabbits were made septic by subcutaneous injection of endotoxin (lipopolysaccharide, LPS) from Escherichia coli at concentrations of 100 or 150 mg LPS´kg21 24 h prior to the experiments. Mitochondrial respiration was measured in saponin-skinned muscle fibers and compared with photometrically detected activities of respiratory chain enzymes as well as with function of perfused hearts. In heart fibers a dosage of 100 mg LPS´kg21 caused a significant decrease of state 3-respiration for the substrates pyruvate (238%), octanoyl-carnitine (238%) and succinate (230%) with correspondingly decreased respiratory control indexes (RCI). In addition, endotoxin caused a decreased temporal stability of the rate of state 3-respiration. At least in part these changes can be attributed to a reduced activity of complex I and III (250%) of the respiratory chain. State 4-respiration rates were not significantly altered. The lowered state 3-respiration in heart mitochondria seems to contribute to the impairment of heart muscle function as detected by an increase of coronary vascular resistance (CVR) in endotoxin-treated hearts. Functional properties of mitochondria from M. Vastus lasteralis were not affected by 100 mg LPS´kg21 but a higher dosage of 150 mg LPS´kg21 caused decreased RCI for the substrates pyruvate (229%) and octanoyl-carnitine (232%). Also the activity of complex I and III was not significantly affected at lower dose of endotoxin but decreased (242%) after treatment with 150 mg LPS´kg21. Results demonstrate the involvement of impaired mitochondria in the pathophysiology of septic organ failure and a tissue specifity of endotoxaemia.

Keywords: Sepsis, Endotoxin, Mitochondria, Heart, Skeletal muscle, LPS

O2k-Network Lab: DE Magdeburg Gellerich FN, AT Innsbruck Oroboros


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Organism: Rabbit  Tissue;cell: Heart, Skeletal muscle  Preparation: Permeabilized tissue  Enzyme: Complex I, Complex III 

Coupling state: LEAK 

HRR: Oxygraph-2k