Hypothermia: depression of tricarboxylic acid cycle flux and evidence for pentose phosphate shunt upregulation

Object. Hypothermia is used in neurosurgery and other surgical disciplines to reduce tissue injury, but the mechanism of such protection remains elusive. The authors have endeavored to delineate the mechanism of neural protection afforded by hypothermia through a study of glucose metabolism. Methods. Nuclear magnetic resonance spectroscopy was used to follow the carbon-13 label from [1-C-13]glucose as it was metabolized through the glycolytic and tricarboxylic acid pathways. Male Sprague-Dawley rats were maintained at either 37.5 degrees C or 31 degrees C and infused with labeled glucose for 10, 30, 60, 100, or 200 minutes (five rats were used for each time point and for each temperature). At the end of the infusion period, the rats' brains were subjected to rapid freeze-funnel fixation. Water soluble metabolites were extracted from samples of the neocortex and hippocampus by using perchloric acid extraction. The fractional enrichment of these metabolites was used to calculate the reaction rate constant of formation and steady-state enrichment for a number of metabolites. Hypothermia resulted in a 30 to 40% depression of metabolism (p < 0.0001) in both the neocortex and hippocampus. Steady-state fractional enrichment of metabolites was also decreased by 20 to 25% with hypothermia (p < 0.0001), implying a loss of label during metabolism. Conclusions. The results of this study suggest that an increased fraction of glucose metabolism was shunted through the pentose phosphate pathway in the presence of hypothermia.