Ten minutes of complete ischemia was produced in 11 dogs by temporary ligation of the aorta. Immediately before the ischemic episode, the dogs received nimodipine, a new calcium entry blocker, 10 micrograms kg-1, i.v., followed by an infusion of 1 microgram kg-1 min-1 for 2 h. Post-ischemic cerebral blood flow and metabolism were measured for 120 min in six dogs. Neurologic recovery was evaluated 48 h post-ischemia in five dogs. The results were compared to previously determined controls. Nimodipine nearly doubled cerebral blood flow in the delayed post-ischemic hypoperfusion period, compared to untreated dogs (approximately 45% versus 25% of pre-ischemic control values), but had no significant effect on metabolism. Nimodipine also improved neurologic recovery. Four of five treated dogs were normal and one was moderately damaged, whereas six of seven controls were either severely damaged or dead. This suggests that the delayed hypoperfusion state occurring after complete cerebral ischemia probably does contribute to the ultimate neurologic damage, and that nimodipine offers a potential protective effect.

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Ten minutes of complete cerebral ischemia was produced in 26 dogs by temporary ligation of the aorta and the venae cavae. Twenty dogs received nimodipine, a calcium entry blocker, 10 micrograms kg-1 i.v. 2 min after the ischemic period, followed by 1 microgram kg-1 min-1 for 2-3 h. Six dogs received only the solvent used for nimodipine. Fourteen dogs received nimodipine for 3 h and were subsequently evaluated neurologically up to 48 h postischemia. In the 12 other dogs, CBF and metabolism were followed for 2 h postischemia while either nimodipine or the solvent only was infused. The results were compared to previously published results for untreated dogs and dogs given nimodipine before the ischemic event. Nimodipine had the same effect on postischemic CBF whether started before or after the ischemic event, nearly doubling the flow when compared with untreated controls, whereas the solvent alone caused only a slight increase in CBF over control. By contrast, nimodipine initiated in the preischemic period significantly improved the neurologic outcome, but when initiated in the postischemic period the results were equivocal, such that the outcome was not significantly different from either the untreated group or the group in which nimodipine was initiated preischemia. Metabolic measurements did not give any indication of a specific effect of nimodipine, nor could the metabolic results be used as an indicator of neurologic outcome. The results are consistent with a beneficial effect of nimodipine following complete cerebral ischemia; however, evaluation of neurologic functional effects will require a more sensitive model.