Prevention of experimental cerebral vasospasm by intracranial delivery of a nitric oxide donor from a controlled-release polymer: toxicity and efficacy studies in rabbits and rats.
Stroke
; 33(11): 2681-6, 2002 Nov.
Article
en En
| MEDLINE
| ID: mdl-12411661
ABSTRACT
BACKGROUND AND PURPOSE:
A reduction in the local availability of nitric oxide (NO) may play a role in the etiology of chronic cerebral vasospasm after subarachnoid hemorrhage (SAH). We investigated the toxicity and efficacy of a locally delivered NO donor from a controlled-release polymer in preventing experimental cerebral vasospasm in rats and rabbits, respectively.METHODS:
Diethylenetriamine/NO (DETA/NO) was incorporated into controlled release ethylene-vinyl acetate (EVAc) polymers. Twenty-eight rats were used in a dose-escalation toxicity study to establish a maximally tolerated dose of DETA/NO-EVAc polymer. In the efficacy experiment, 20 rabbits were assigned to 4 experimental groups (n=5 per group) sham operation; SAH only; SAH+empty EVAc polymer; and SAH+DETA/NO-EVAc polymer. Treatment was initiated 30 minutes after blood deposition. Basilar artery lumen patency was assessed 72 hours after hemorrhage to evaluate the efficacy of DETA/NO in preventing cerebral vasospasm.RESULTS:
In the toxicity study, a dose of 3.4 mg/kg was identified as the LD(20) (dose with 20% mortality during the study period) of this DETA/NO formulation. Brain histology revealed hemorrhage and ischemic changes at the implantation site associated with high concentrations of DETA/NO. In the efficacy study, treatment with DETA/NO-EVAc polymer resulted in a significant decrease in basilar artery vasospasm compared with no treatment (93.0+/-4.9% versus 71.4+/-11.9%; P=0.035) or compared with treatment with blank EVAc polymer (93.0+/-4.9% versus 73.2+/-6.4%; P=0.003).CONCLUSIONS:
Local delivery of DETA/NO prevents vasospasm in the rabbit basilar artery. Local delivery of DETA/NO via polymers is a safe and effective strategy for preventing cerebral vasospasm after SAH in this model.
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Bases de datos:
MEDLINE
Asunto principal:
Poliaminas
/
Hemorragia Subaracnoidea
/
Donantes de Óxido Nítrico
/
Vasoespasmo Intracraneal
Idioma:
En
Revista:
Stroke
Año:
2002
Tipo del documento:
Article
País de afiliación:
Estados Unidos