Nimodipine Improves Outcome when Given after Complete Cerebral Ischemia in Primates

Abstract

Twenty-seven pigtailed monkeys (Macaca nemestrina) were subjected to 17 min of complete cerebral ischemia followed by 96 h of intensive care treatment. Of the monkeys 14 were assigned randomly to the treatment group and received nimodipine 10 .mu.g .cntdot. kg-1 5 min postischemia followed by 1 .mu.g .cntdot. kg-1 .cntdot. min-1 for 10 h. Six monkeys (3 treated) failed to meet preestablished protocol criteria and were excluded. The remaining treated and untreated monkeys were well matched for age, sex and other physiologic variables. Neurologic outcome at 96 h postischemia was significantly better in the nimodipine-treated monkeys than in the controls. Of the 11 treated animals 8 had an apparent normal level of consciousness. Of these, 4 had no detectable neurologic deficits and a 5th had only a slight motor apraxia. Only 2 of the 10 untreated animals had an apparent normal level of consciousness and all had major neurologic deficits. Histopathologic examination showed variable ischemic neuronal change and infarction to involve gray matter in distal arterial perfusion zones. Significant white matter changes were not observed. A histologic scoring system yielded a significant correlation between neurologic function and histopathologic findings. Nimodipine improves the neurologic outcome when given after an episode of complete cerebral ischemia in primates, and controlled clinical trials in patients resuscitated after cardiac arrest are recommended.