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

The involvement of mitochondrial dysfunction in septic disturbances of tiss ues is controversial. The aim of this study was to investigate the effects of endotoxin-induced sepsis on the function of heart and skeletal muscle mi tochondria. Rabbits were made septic by subcutaneous injection of endotoxin (lipopolysaccharide, LPS) from Escherichia coli at concentrations of 100 o r 150 mug LPS.kg(-1) 24 h prior to the experiments. Mitochondrial respirati on was measured in saponin-skinned muscle fibers and compared with photomet rically detected activities of respiratory chain enzymes as well as with fu nction of perfused hearts. In heart fibers a dosage of 100 mug LPS.kg(-1) caused a significant decreas e of state 3-respiration for the substrates pyruvate (-38%), octanoyl-carni tine (-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 change s 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 c oronary vascular resistance (CVR) in endotoxin-treated hearts. Functional properties of mitochondria from M. Vastus lasteralis were not af fected by 100 mug LPS.kg(-1) but a higher dosage of 150 mug LPS.kg(-1) caus ed 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 m ug LPS.kg(-1). Results demonstrate the involvement of impaired mitochondria in the pathoph ysiology of septic organ failure and a tissue specifity of endotoxaemia.