Effects of Hypothermia on Excitatory Amino Acids and Metabolism in Stroke Patients

Abstract

Background and Purpose — The objective of this study was to assess the effect of therapeutic moderate hypothermia on excitatory amino acids and metabolism by applying cerebral microdialysis in patients suffering from space-occupying middle cerebral artery infarction. Methods — This was an open, prospective, observational study of 12 patients undergoing moderate hypothermia (33°C) as rescue therapy for large, life-threatening middle cerebral artery infarction. Microdialysis probes were placed concomitantly with intracranial pressure (ICP) measuring devices in the frontal lobe of the infarcted and/or noninfarcted hemisphere. Using the CMA 600 Microdialysis Autoanalyzer, we analyzed glutamate, glycerol, pyruvate, and lactate. Results — According to follow-up cranial CT scans, 3 different compartments of microdialysis measurements could be defined. First, noninfarcted brain tissue had stable dialysate concentrations but a significant effect of hypothermia on glutamate (2.6 versus 3.6 μmol/L), lactate (1.8 versus 3 mmol/L), and pyruvate (50 versus 95.8 μmol/L). Second, measurements from peri-infarct tissue had a significant effect of hypothermia on glutamate (4.8 versus 12.6 μmol/L), glycerol (58 versus 82 μmol/L), lactate (0.7 versus 1.3 mmol/L), and pyruvate (13.3 versus 36.8 μmol/L). Third, dialysate concentrations obtained from irreversibly damaged tissue were excessive for glutamate (453 μmol/L), glycerol (1187 μmol/L), lactate (12 μmol/L), and pyruvate (4 μmol/L). In this extreme compartment, no effect of hypothermia was observed. Conclusions — Cerebral microdialysis is a safe and feasible bedside method for neurochemical monitoring indicating normal brain tissue, potentially salvageable brain tissue, and irreversibly damaged areas in stroke. We could demonstrate that hypothermia decreases glutamate, glycerol, lactate, and pyruvate in the “tissue at risk” area of the infarct but not within the infarct core. Thus, future treatment strategies for life-threatening stroke should be guided by close neurochemical monitoring.