Different sensitivity of rabbit heart and skeletal muscle to endotoxin-induced impairment of mitochondrial function.

The involvement of mitochondrial dysfunction in septic disturbances of tissues is controversial. The aim of this study was to investigate the effects of endotoxin-induced 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 microg LPS.kg(-1) 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 microg LPS.kg(-1) caused a significant decrease of state 3-respiration for the substrates pyruvate (-38%), octanoyl-carnitine (-38%) and succinate (-30%) 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 + III (-50%) 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 microg LPS.kg(-1) but a higher dosage of 150 microg LPS.kg(-1) caused decreased RCI for the substrates pyruvate (-29%) and octanoyl-carnitine (-32%). Also the activity of complex I + III was not significantly affected at lower dose of endotoxin but decreased (-42%) after treatment with 150 microg LPS.kg(-1). Results demonstrate the involvement of impaired mitochondria in the pathophysiology of septic organ failure and a tissue specificity of endotoxaemia.