Metabolic adjustments to dynamic hypoxic hypoxemia in feline brain tissue

Three different metabolic models were incorporated in a compartmental simulation of brain tissue pO2 response to rapid changes in arterial pO2. The first was the frequently utilized constant metabolism assumption. The second model was a 4-step kinetic simplification of glucose conversion to CO2 with an intermediate reversible reaction of pyrovate to lactate. The most sophisticated model was a new 11-step reaction scheme with the same start and end points accounting for glycolysis, the tricarboxylic acid cycle, and oxidative phosphorylation. A unique representation was derived for the oxygen consumption depending on reduced cytochrome a3+(3) consistent with diverse observations in the literature. The theoretical predictions were compared to previously published cortical tissue pO2 recordings from detailed experiments with pentobarbital anesthetized cats. The 11-step metabolic model invariably provided the best match between the theoretical calculations and the observed responses. These results indicate that cellular metabolism rapidly adjusts to changes in O2 in a manner which reduces the tissue pO2 fluctuation. In concert with the large compensatory arterial blood flow response there was extensive damping of intracellular pO2 compared to arterial O2 changes.