Microcirculatory dysfunction precedes changes in evoked potentials in endotoxin-induced sepsis syndrome in rats

Background: Somatosensory evoked potentials are early indicators of septic encephalopathy, whereas in many other organs microcirculatory failure was shown to precede organ dysfunction. To assess the role of microcirculatory failure in the brain we assessed activation-flow coupling in a rat model of endotoxic shock.

Material and Methods: Chloralose-anesthetized rats (n=10) were subjected to electric forepaw stimulation. Over the somatosensory cortex electrical activity and hemodynamic responses were recorded simultaneously with surface electrodes and laser Doppler flowmetry. After baseline recordings 1mg/kg or 5mg/kg lipopolysaccharide from E. coli was given i.v. to induce a moderate or severe sepsis syndrome. Resting cerebral blood flow velocity, somatosensory evoked potentials and flow velocity responses as well as blood pressure and blood gases were investigated at regular time points up to 270min. At the end lactate, glucose, NSE and S-100B levels were measured.

Results: Although in both groups macrocirculation was still intact, blood pressure levels remained above the lower limit of cerebral autoregulation, and cerebral hyperaemia occurred, microcirculatory dysfunction emerged. Evoked flow velocities decreased significantly in the severe sepsis group 60min after sepsis induction although SEP amplitudes were similar between groups at that time point. SEP amplitudes differed between groups first 180min after sepsis induction showing highest differences at the end of experiments.

Conclusions: Microcirculatory failure is a generator of sepsis related organ dysfunction in the brain. The uncoupling indicates insufficient blood supply of active neurons and thus in part may explain the succeeding drop in evoked potentials. Occurrence of cerebral hyperemia or maintenance of macrocirculation are insufficient parameters to assess risk of sepsis related brain damage.