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 LD20 (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.
Original language | English (US) |
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Pages (from-to) | 2681-2686 |
Number of pages | 6 |
Journal | Stroke |
Volume | 33 |
Issue number | 11 |
DOIs | |
State | Published - Nov 1 2002 |
Keywords
- Nitric oxide
- Polymers
- Rabbits
- Rats
- Subarachnoid hemorrhage
- Vasospasm, intracranial
ASJC Scopus subject areas
- Clinical Neurology
- Cardiology and Cardiovascular Medicine
- Advanced and Specialized Nursing