Cerebral energy metabolism during induced mitochondrial dysfunction

In patients with traumatic brain injury as well as stroke, impaired cerebral oxidative energy metabolism may be an important factor contributing to the ultimate degree of tissue damage. We hypothesize that mitochondrial dysfunction can be diagnosed bedside by comparing the simultaneous changes in brain tissue oxygen tension (PbtO(2)) and cerebral cytoplasmatic redox state. The study describes cerebral energy metabolism during mitochondrial dysfunction induced by sevoflurane in piglets.

Ten piglets were included, seven in the experimental group (anesthetized with sevoflurane) and three in the control group (anesthetized with midazolam). PbtO(2) and cerebral levels of glucose, lactate, and pyruvate were monitored bilaterally. The biochemical variables were obtained by intracerebral microdialysis.

All global variables were within normal range and did not differ significantly between the groups except for blood lactate that was slightly higher in the experimental group. Mitochondrial dysfunction was observed in the group of animals initially anesthetized with sevoflurane. Cerebral glucose was significantly lower in the experimental group than in the control group whereas lactate and lactate/pyruvate ratio were significantly higher. Pyruvate and tissue oxygen tension remained within normal range in both groups. Changes of intracerebral variables indicating mitochondrial dysfunction were present already from the very start of the monitoring period.

Intracerebral microdialysis revealed mitochondrial dysfunction by marked increases in cerebral lactate and lactate/pyruvate ratio simultaneously with normal levels of pyruvate and a normal PbtO(2). This metabolic pattern is distinctively different from cerebral ischemia, which is characterized by simultaneous decreases in PbtO(2) and intracerebral pyruvate.