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 iV-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 = ll,/?<0.001). During reperfusion, the lactate level in the treated group was reduced (/?<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 iV-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 (/?<0.05). There was a significant correlation between end-ischemic tissue pH and hippocampal damage (r=-0.73,/?<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. (Stroke 1991^22^43-350)