Bimodal treatment with nimodipine and low‐molecular‐weight dextran for focal cerebral ischemia in the rat

Abstract

We compared the effects of intravenous treatment with combined low-molecular-weight dextran and nimodipine (n = 9), or placebo (n = 10), on local cerebral blood flow after occlusion of the left middle cerebral and common carotid artery in the rat. Treatment for a total of 4 hours with low-molecular-weight dextran (5 mg/kg/min) and nimodipine (0.25 microgram/kg/min) produced a decrease in hematocrit from 46 +/- 1 to 33 +/- 1% at the end of the study and a statistically significant increase in local cerebral blood flow, when compared to the control group, in 6 regions of interest: the territories of the right middle (p = 0.01), right anterior (p = 0.007), and left anterior cerebral arteries (p = 0.001); the superior (p = 0.03) and inferior border zone (p = 0.003); and white matter in the right hemisphere (p = 0.04). The ischemic volume, defined as brain volume with a cerebral blood flow of less than the critical level of 25 ml/min/100 gm was determined as a percentage of total brain volume for the control and treatment groups. The group treated with low-molecular-weight dextran and nimodipine showed a 31% decrease in ischemic volume (p = 0.03). These results indicate that a bimodal approach with low-molecular-weight dextran and nimodipine can be safely used in a model of acute stroke and has a beneficial effect on local cerebral blood flow and ischemic volume when compared with control subjects. After 4 hours, the potential exists that this treatment is therapeutic, assuming that the ischemic volume progresses to infarction.