Local Delivery of Ibuprofen via Controlled-release Polymers Prevents Angiographic Vasospasm in a Monkey Model of Subarachnoid Hemorrhage
| Autor: | Rafael J. Tamargo, Gustavo Pradilla, Federico G. Legnani, Kieran P. Murphy, Quoc Anh Thai, Richard E. Clatterbuck, Philippe Gailloud |
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| Rok vydání: | 2005 |
| Předmět: |
Male
Subarachnoid hemorrhage Lumen (anatomy) Ibuprofen medicine.artery medicine Animals Vasospasm Intracranial cardiovascular diseases business.industry organic chemicals Vasospasm Subarachnoid Hemorrhage medicine.disease Cerebral Angiography nervous system diseases Disease Models Animal Macaca fascicularis Treatment Outcome medicine.anatomical_structure Delayed-Action Preparations Anesthesia Middle cerebral artery Toxicity Polyvinyls Surgery Neurology (clinical) Pharmaceutical Vehicles medicine.symptom Subarachnoid space business Vasoconstriction medicine.drug |
| Zdroj: | Operative Neurosurgery. 57:184-190 |
| ISSN: | 2332-4260 2332-4252 |
| Popis: | OBJECTIVE: Adhesion and migration of leukocytes into the periadventitial space play a role in the pathophysiology of vasospasm after subarachnoid hemorrhage (SAH). Intercellular adhesion molecule-1 is a determinant cell adhesion molecule involved in this process. Ibuprofen has been shown to inhibit intercellular adhesion molecule-1 upregulation and prevent vasospasm in animal models of SAH. In this study, we report the toxicity and efficacy of locally delivered ibuprofen incorporated into controlled-release polymers to prevent vasospasm in a monkey model of SAH. METHODS: Ibuprofen was incorporated into ethylene-vinyl acetate (EVAc) polymers at 45% loading (wt:wt). For the toxicity study, cynomolgus monkeys (n = 5) underwent surgical implantation of either blank/EVAc polymers (n = 3) or 45% ibuprofen/EVAc polymers (n = 2) in the subarachnoid space, were followed up for 13 weeks, and were killed for histopathological analysis. For the efficacy study, cynomolgus monkeys (n = 14) underwent cerebral angiography 7 days before and 7 days after surgery and SAH and were randomized to receive either a 45% ibuprofen/EVAc polymer (n = 7; mean dose of ibuprofen, 6 mg/kg) or blank EVAc polymers (n = 7) in the subarachnoid space. Angiographic vasospasm was determined by digital image analysis. Student's t test was used for analysis. RESULTS: Animals implanted with ibuprofen polymers showed no signs of local or systemic toxicity. Animals treated with ibuprofen polymers had 91 ± 9% lumen patency of the middle cerebral artery, compared with 53 ± 11% of animals treated with blank/EVAc polymers (P < 0.001). CONCLUSION: Ibuprofen polymers are safe and prevent angiographic vasospasm after SAH in the monkey model. These findings support the role of cell adhesion molecules and inflammation in the pathophysiology of vasospasm. |
| Databáze: | OpenAIRE |
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