Alterations of mitochondrial metabolism and protein concentrations in subacute septicemia

Male Sprague-Dawley rats were made septic by cecal ligation for a period of 6 days. Sham-operated rats were used as control animals. Septic rats developed gram-negative bacteremia within 18 to 24 h. Blood cultures were positive for Escherichia coli, Proteus spp., and Klebsiella spp. in all cases. Significant loss of body weight was observed in septic rats during the 6-day period, whereas control rats exhibited a steady gain in body weight after the second postoperative day. Liver and muscle mitochondria were isolated and analyzed 6 days after the operation in control and septic rats. Liver mitochondrial cytochrome a(a3), b, and c concentrations were normal in septic rats. Oxygen utilization rates in state 3 (during ATP synthesis) were also within the normal range. State 4 respiratory rates, however, were increased with glutamate and pyruvate as substrates, resulting in low respiratory control ratios in septic rats. Muscle mitochondria from septic rats exhibited several abnormalities: the yield of cytochromes b, c, and a(a3) per gram of tissue was 34% below normal in septic rats. ATP synthesis rates declined significantly with pyruvate as substrate. Respiratory control ratios were below normal with all substrates studied except glutamate. These data are in agreement with previous reports on loss of muscle proteins and abnormalities in energy fuel utilization in septic patients.