Effects of endotoxemia on the redox level of brain cytochrome a,a3 in rats.

We conducted the present study to determine the effect of endotoxin challenge on brain oxidative metabolism, after finding evidence in previous studies suggesting early uncoupling of mitochondrial oxidative phosphorylation in the rat small intestine during endotoxemia. Twenty male Sprague-Dawley rats were divided into two groups (N = 10 each) which received E. coli endotoxin (20 mg/kg BW) or an equal volume of 0.9% saline (1 ml/kg) by i.v. bolus. Catheter implantation and the subsequent data collection were conducted using isoflurane anesthesia with controlled ventilation. Hemodynamic and metabolic data were recorded for 30 min before and 60 min after endotoxin or saline injection. Tissue oxidative metabolism was monitored in vivo using differential multiwavelength near-infrared spectrophotometry. Optrodes were positioned on either side of the rat's head (transillumination mode) to monitor the redox state of mitochondrial cytochrome a,a3 (AA3) as well as the supply of oxygen to the brain as reflected by tissue oxyhemoglobin (HbO2). In contrast to our previous results for the small intestine, where the decrease in AA3 oxidation level was disproportionately greater than the concomitant HbO2 decrease, we found that the endotoxin-induced impairment in blood flow to the head was associated with a decrease in brain AA3 redox level, which was proportional to the decrease in tissue HbO2. This finding of an apparent oxygen-dependent AA3 redox shift in the brain during endotoxemia is similar to previous findings of others in hemorrhagic hypotension and hypoxic hypoxia. Possible mechanisms for the different mitochondrial AA3 redox responses to endotoxin in the brain and small intestine are discussed.