Artikel
The effect of an intracisternal Nimodipine slow-release system on cerebral vasospasm after experimental subarachnoid hemorrhage in the rat
Der Effekt eines intrazisternalen Nimodipin slow-release Systems auf den zerebralen Vasospasmus nach experimenteller Subarachnoidalblutung der Ratte
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Veröffentlicht: | 8. Mai 2006 |
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Gliederung
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Objective: Intracisternal slow delivery systems are a promising concept of local treatment of cerebral vasospasm after subarachnoid hemorrhage (SAH). The purpose of the actual study was to investigate for the first time an intracisternal Nimodipine slow-release system after induced SAH in the rat.
Methods: 28 male Wistar rats of 200-300 g were divided into four groups; 1) SAH group plus intracisternal Nimodipine slow-release system (0.5mg/day), 2) SAH only group, 3) SAH group plus placebo and 4) sham-operated group. Vasospasm was induced by injecting 0.2ml autologous blood into the cisterna magna. The placebo or drug delivery pellet was implanted in a muscle pouch open to the cisterna magna 10 minutes after the blood injection. Vasospasm was analyzed 5 days later by means of orthograde pressure-controlled angiography. Analysis of vasospasm was carried out with a newly developed software assisted technique measuring the exact filling of the middle cerebral artery in comparison to the extracranial stapedial artery.
Results: The sham-operated group was used as the baseline for the angiographic evaluation. The average ratio of middle cerebral and stapedial artery filling intensity was quantified as 0.74% in this group. In comparison to the baseline group, the SAH only group (0.70%) and the SAH plus placebo group (0.66%) showed no statistically significant evidence of cerebral vasospasm. The group of SAH plus intracisternal Nimodipine slow-release system showed a significant relaxation of the middle cerebral artery in contrast to the SAH only and the SAH plus placebo groups (0.83%, p=0.011, two-sided t-test).
Conclusions: An intracisternal slow delivery system with a release of 0.5mg Nimodipine per day leads to significant intracranial arterial relaxation after experimental subarachnoid hemorrhage in the rat. Therefore, the Nimodipine intracisternal slow-delivery system promises the potential of local treatment of vasospasm in the future. Exact release rates for effective CSF levels in patients must be determined prior to the clinical introduction of the new modality.