EFFECTS OF ENDOTOXEMIA ON THE REDOX LEVEL OF BRAIN CYTOCHROME-A,A3 INRATS

We conducted the present study to determine the effect of endotoxin ch allenge on brain oxidative metabolism, after finding evidence in previ ous studies suggesting early uncoupling of mitochondrial oxidative pho sphorylation in the rat small intestine during endotoxemia. Twenty mal e 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% s aline (1 ml/kg) by i.v. bolus. Catheter implantation and the subsequen t data collection were conducted using isoflurane anesthesia with cont rolled ventilation. Hemodynamic and metabolic data were recorded for 3 0 min before and 60 min after endotoxin or saline injection. Tissue ox idative metabolism was monitored in vivo using differential multiwavel ength near-infrared spectrophotometry. Optrodes were positioned on eit her side of the rat's head (transillumination mode) to monitor the red ox 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 d ecrease in AA3 oxidation level was disproportionately greater than the concomitant HbO2 decrease, we found that the endotoxin-induced impair ment in blood flow to the head was associated with a decrease in brain AA3 redox level, which was proportional to the decrease in tissue HbO 2. 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 br ain and small intestine are discussed.