Brain temperature modulations during global ischemia fail to influence extracellular lactate levels in rats

While brain tissue lactate increases during cerebral ischemia and is known to be important in the pathogenesis of ischemic brain injury, patterns of extracellular lactate accumulation have been less well characterized, and the influence of brain temperature has not been previously investigated. Mild brain temperature modulations are known to affect the outcome of ischemia dramatically. This study examined changes of extracellular lactate during and after global cerebral ischemia, in which intraischemic brain temperature was held at either 30 degrees C, 37 degrees C, or 39 degrees C.

Halothane-anesthetized fasted male Wistar rats underwent 20 minutes of global cerebral ischemia produced by bilateral carotid artery occlusions plus systemic hypotension (40 to 50 mm Hg). Rectal temperature was maintained at 37 degrees C throughout, and intraischemic brain temperature was held at either 30 degrees C (n = 6), 37 degrees C (n = 5), or 39 degrees C (n = 5). Before and after the ischemic insult, brain temperature was maintained at 37 degrees C in all groups. A microdialysis cannula was implanted in the right dorsolateral striatum and perfused with Ringer's solution. Dialysate samples were collected at 10-minute intervals before, during, and after ischemia and were analyzed for lactate by enzymatic-fluorometric techniques.

In all groups, extracellular lactate rose during ischemia and peaked at 10 to 30 minutes of recirculation. Maximal extracellular lactate elevations were sevenfold, eightfold, and eightfold above control in the 30 degrees C, 37 degrees C, 39 degrees C groups, respectively. Significant elevations with respect to control were observed in all groups at 10 to 30 minutes of recirculation. In the 30 degrees C group, these elevations above control were also significant at the 10- and 20-minute ischemic time points (P = .001). At 30 minutes of recirculation, however, lactate levels were lower in the 30 degrees C rats than in the other groups.

These data provide evidence that extracellular lactate accumulation is not a crucial determinant of ischemic brain injury. Our results suggest that the increased lactate release during ischemia and the accelerated clearance of lactate during recirculation might contribute in part to the neuroprotection of intraischemic hypothermia.