Brain edema, autoregulation, and calcium antagonism. An experimental study with nimodipine.

We investigated the effects of the calcium entry blocker nimodipine on cerebral autoregulation, BBB, and vasogenic edema in animal experiments. In the first series of rats, ICBF was measured with H2 clearance using a balanced multiwire surface electrode. Variations in blood pressure (SAP), which was measured via femoral catheter, were induced by infusion of norfenefrine (pressure increase) and by hemorrhage (pressure decrease). The effect of SAP on the cerebral microcirculation was evaluated. In control animals receiving nimodipine, a typical autoregulation plateau was found. In rats treated with nimodipine infusion (12-14 micrograms/kg/min), 1CBF was considerably elevated at all blood pressure levels above 50 mm Hg, and in the steep 1CBF/SAP correlation, the autoregulation plateau was almost suspended. In a second series of randomized rats, the effect of nimodipine on BBB was investigated after Evans blue infusion. When a SAP of 180 mm Hg systolic was maintained for 6 min, a diffuse Evans blue staining was seen in 70% of the nimodipine animals (break-through of BBB). In the third series of rats, the effect of nimodipine on cold injury edema was investigated. Nimodipine (1 mg i.p.) considerably decreased the SAP; Edema formation measured by water and Na+ content 24 hr after trauma was then reduced. However, if the decrease in SAP was in part prevented by norfenefrine application, the rats receiving nimodipine developed significantly more edema. Brain water and sodium contents were markedly increased in both hemispheres. The results indicate an interference of nimodipine with cerebral autoregulation, and a BBB disruption may occur at lower SAP. If the BBB is impaired, nimodipine may considerably intensify edema formation. Nimodipine and similar calcium entry blockers should therefore only be used with caution in acute brain damage.