EFFECTS OF DEXTROMETHORPHAN ON RAT-BRAIN DURING ISCHEMIA AND REPERFUSION ASSESSED BY MAGNETIC-RESONANCE SPECTROSCOPY

Using proton and phosphorus magnetic resonance spectroscopy, we evaluated the metabolic effects of preischemic administration of the N-methyl-D-aspartate antagonist dextromethorphan (50 mg/kg i.p.) during global forebrain ischemia and subsequent reperfusion in rats. Dextromethorphan-treated animals (n = 10) showed less lactate formation during ischemia than untreated animals (n = 11, p < 0.001). During reperfusion, the lactate level in the treated group was reduced (p < 0.05). Tissue pH declined less in the treated group during ischemia (p < 0.01). There was no difference in the phosphocreatine/inorganic phosphate peak height ratio between groups. During ischemia, the N-acetylaspartate resonance peaks decreased in both groups. Histologic damage assessed in the hippocampal CA1 region 7 days after the ischemic insult was more severe in the untreated group (p < 0.05). There was a significant correlation between end-ischemic tissue pH and hippocampal damage (r = 0.73, p < 0.05). In the dextromethorphan-treated animals, 90% of the rats survived compared with 47% of the untreated animals (p < 0.05). These results support findings in previous studies that dextromethorphan attenuates ischemic damage.