Pathophysiology of sepsis-associated brain dysfunction: an experimental study of cerebral microdialysis and mitochondrial function

Abstract

Introduction: Pathophysiology of brain dysfunction associated with sepsis is still poorly understood. Our purpose was to study the metabolic alterations and mithocondrial dysfunction in a clinically relevant model of septic shock. Methods: Twelve anesthetized, invasively monitored, and mechanically ventilated pigs were allocated to a sham procedure (n = 5) or sepsis (n = 7), in which peritonitis was induced by intra-abdominal injection of autologous faeces. Animals were studied until spontaneous death or for a maximum of 24 hours. In addition to global hemodynamic and laboratory assessment, intracranial pressure and cerebral microdyalisis were assessed 6, 12, 18 and 24 hours after sepsis induction. After death, brain were removed and brain homogenates were studied to assess mithocondrial dysfunction. Results: All septic animals developed a hyperdynamic state associated with organ dysfunction. In the septic animals, there was a progressive increase in L/P ratio and glycerol, as well as a progressive decrease in brain glucose concentration during the study period. The comparison between control and septic animals and the analysis of brain homogenates are undergoing. Conclusions: In this model of peritonitis, cerebral metabolism was derranged, with increasing levels of L/P ratio and decreasing levels of brain glucose during study period. These alterations may play a role in the pathogenesis of sepsis-associated encephalopathy.