Evoked potentials and activation flow coupling in endotoxin mediated sepsis syndrome in rats

During sepsis progression microcirculatory dysfunction precedes macrocirculatory failure partly explaining occurrence of early organ dysfunction. The matter concerning microcirculatory dysfunction in the brain under septic conditions is less clear. Activation-flow coupling denotes a principle adapting local cerebral blood flow in accordance to the metabolic needs of the neurons. We utilized a rat model of endotoxic shock and investigated the activation flow coupling under sepsis progression. Chloralose-anesthetized rats (n=10) were subjected to electric forepaw stimulation. Over the somatosensory cortex electrical activity and flow responses were recorded with surface electrodes and laser Doppler. After baseline recordings 5 mg/kg lipopolysaccharide from E. coli was given i.v. and activation flow coupling, blood pressure, and blood gases were investigated at regular time points up to 270 min. At the end lactate, glucose, NSE and S-100B levels were measured. All rats developed signs of septic shock. SEP amplitudes and latencies as well as evoked flow responses changed significantly. Changes in evoked flow responses preceded SEP reductions leading to a sigmoid rather than linear relationship between signals indicating insufficient blood supply. Dividing rats into two groups one with more and one with less severe changes in pH (7.40±0.04 vs. 7.35±0.06), blood pressure (77±14 vs. 55±13 mmHg) and lactate levels (1.4±0.5 vs. 3.3±0.6 mmol/L) it appeared that occurrence of cerebral hyperemia (+40% for both groups) and NSE-levels (1.9±0.4 vs. 2.2±0.3 ng/ml) were identical between groups. SEP latencies (10±0.6 vs. 12±0.8 ms) and S-100B (5.3±2.3 vs. 13.5±1.3 ng/ml) were significantly higher in the severe sepsis group whereas SEP amplitudes (270 min: 13 ± 2.1 vs. 8 ± 4.2 μV) and evoked flow responses (270 min: 10±8 vs. 6±5AUC [area under the curve]) showed only a trend to lower values. More or less independent from the severity of the sepsis syndrome microcirculatory dysfunction precedes changes in electrical parameters leading to an insufficient blood supply of active neurons. This finding contrasts with occurrence of cerebral hyperemia during sepsis progression and is in line with concepts of microcirculatory failure explaining occurrence of early septic encephalophathy. The constellation of higher S-100B rather than NSE levels might be explained by a disruption of astrocytic end feet due to blood brain barrier leakage. Since astrocytes are involved in the activation flow coupling further studies are needed to investigate a possible relation.