Impaired energy metabolism in hearts of septic baboons: Diminished activities of Complex I and Complex II of the mitochondrial respiratory chain

Recent findings support the view that the bioenergetic part of septic organ failure is not caused by insufficient supply of oxygen but by disturbances of the mitochondrial function. Therefore, the aim of the present study was to investigate key enzymes of energy metabolism in septic hearts to answer the question whether or not impairment of mitochondrial or glycolytic enzy mes occur under these conditions. For this purpose the well established mod el of septic baboons was used. Baboons under general anesthesia were made s eptic by infusion of Escherichia coli, Single challenge with infusion of hi gh amounts of bacteria was compared with a multiple challenge protocol (les s bacteria infused). Some animals obtained no E. coli (sham). The hearts of the baboons were removed after 72 h (survival: yes) or after death (surviv al, no) of the animals, frozen in liquid nitrogen, and stored at -80 degree s C until spectrophotometrical measurement of nine mitochondrial and glycol ytic enzymes. A reduction of the activity of NADH:cytochrome-c-reductase (C omplex I + III) to 67% and succinate:cytochrome-c-reductase (Complex II + I II) to 45% was found in the hearts of surviving animals after infusion of h igh amounts of bacteria. After multiple challenge with lesser amounts of ba cteria, no significant changes in enzyme activity were detectable. After le thal septic shock, activities of Complex I + III (12%) and Complex II + III (13%) as well as of phosphofructokinase (16%) were found to be strongly di minished, Decylubiquinol:cytochrome-c-reductase (Complex III, 59%), cytochr ome-c-oxidase (51%), succinate dehydrogenase (60%), glucosephosphate isomer ase (61%), lactate dehydrogenase (61%), and citrate synthase (120%) were le ss or unaffected. Similar but less pronounced effects were found after infu sion of lesser amounts of bacteria. By means of inhibitor titrations of suc cinate: cytochrome-c-reductase, it was shown that the loss of activity is n ot caused by Complex III but by disturbances in Complex II. It is concluded that E. coil-induced sepsis causes decreased activities of Complex I and C omplex II in baboon heart mitochondria in a dose-dependent manner.