Effects of Dextromethorphan on Regional Cerebral Blood Flow in Focal Cerebral Ischemia

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Abstract
Dextromethorphan (DM), a noncompetitive NMDA antagonist, has been demonstrated to reduce ischemic neuronal damage and edema, but DM's influence on cerebral blood flow has not been extensively studied. In this investigation, it is shown that DM has significant effects on regional cerebral blood flow (rCBF) patterns in a rabbit model of focal cerebral ischemia. rCBF was measured using radioactive microspheres following a 1 h permanent occlusion of the left internal carotid, anterior cerebral, and middle cerebral arteries in rabbits. Somatosensory evoked potentials (SEPs) were used to assess the degree of ischemia; only animals where SEPs were completely abolished were used for a frequency distribution analysis of rCBF. It was found that there were significantly more regions with lower flows in animals treated with normal saline (NS) ( n = 7) compared to animals treated with DM ( n = 7) ( p < 0.05, ipsilateral left side; p < 0.001, contralateral right side). The frequency distribution medians were 27.5 ml 100 g−1 min −1 (left) and 70.0 ml 100 g−1 min−1 (right) in the NS group vs. 34.5 ml 100 g−1 min−1 (left) and 80.5 ml 100 g−1 min−1 (right) in the DM group. The left and right hemispheric regional means were 29.4 ± 20 and 74.3 ± 23 ml 100 g−1 min−1, respectively, in the NS group vs. 34.4 ± 16 and 91.0 ± 28 ml 100 g−1 min−1, respectively, in the DM group. However, there were no significant differences in global CBF between the NS group (33.1 ± 18 and 79.2 ± 20 ml 100 g−1 min−1) and the DM group (35.0 ± 10 and 92.0 ± 21 ml 100 g−1 min−1) in both left and right hemispheres, respectively. These results demonstrate that DM has effects on rCBF in focal cerebral ischemia, although it is unclear if these changes represent primary effects of DM on cerebrovascular function, or secondary effects of neuronal protection.