Effect of nimodipine in treatment of experimental focal cerebral ischaemia

Despite the voluminous current literature the potential of nimodipine to modify the outcome in experimental cerebral ischaemia remains a controversial matter. The authors have evaluated in controlled double blind experiments the influence of a continuous i.v. infusion of the drug (1 microgram kg-1 min-1) upon infarct size, histopathology and neurological outcome in rats with permanent middle cerebral artery (MCA) occlusion. The infusion was started 20 min before induction of ischaemia and continued 4 hours thereafter. The nimodipine treated animals were subdivided into hypotensive (MABP lower than 85 mmHg for more than 5 min after arterial occlusion) and normotensive groups. Infarction size, documented by TTC, H&E and Nissl staining was significantly smaller (p less than 0.001) in nimodipine normotonic rats than the lesions in placebo and saline treated rats, as well compared with hypotonic nimodipine animals (largest infarction). These differences were found to be entirely at the expense of the cortical (frontoparietal) component of the lesion, suggesting 'penumbra' action of the drug. Moreover, nimodipine normotonic rats displayed lower cortical neuronal injury in the periinfarct zone. These findings were corroborated by corresponding better neurological scores. Our results indicate that nimodipine is effective in reducing focal cerebral ischaemia, provided the MABP is maintained higher than 85 mmHg.