Trumbeckaite 2001 Eur J Biochem
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. |
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 LPSΒ΄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 LPSΒ΄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 LPSΒ΄kg21 but a higher dosage of 150 mg LPSΒ΄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 LPSΒ΄kg21. Results demonstrate the involvement of impaired mitochondria in the pathophysiology of septic organ failure and a tissue specifity of endotoxaemia. β’ Keywords: Sepsis, Endotoxin, Mitochondria, Heart, Skeletal muscle, LPS
β’ O2k-Network Lab: DE Magdeburg Gellerich FN, AT Innsbruck Oroboros
Labels:
Organism: Rabbit
Tissue;cell: Heart, Skeletal muscle
Preparation: Permeabilized tissue
Enzyme: Complex I, Complex III
Coupling state: LEAK
HRR: Oxygraph-2k